Changes in renal function and indicators in chronic hepatitis B patients undergoing antiviral therapy for 48 weeks: A prospective cohort study in China

Changes in renal function and indicators in chronic hepatitis B patients undergoing antiviral therapy for 48 weeks: A prospective cohort study in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Changes in renal function and indicators in chronic hepatitis B patients undergoing antiviral therapy for 48 weeks: A prospective cohort study in China jinhua Zhao, Wu Lili, Xiao an Yang, zhi liang Gao, Hong Deng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8719411/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background There is limited research comparing the renal safety of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) when used with pegylated interferon (pegIFN) in patients with chronic hepatitis B (CHB). Here, renal function changes in CHB patients were compared between treated with pegyIFN combined with ETV or TDF. Methods 713 patients with the combination therapy of pegIFN with ETV or TDF were included in a matched analysis comparing outcomes between cured (HBsAg < 0.05IU/mL) and uncured patients, while 104 patients received pegIFN alone as a control group for comparison with the pegIFN-ETV and pegIFN-TDF treatment groups. The primary outcome was the change in renal function. Patients were categorized into stage 1 or stage 2 based on baseline estimated glomerular filtration rate (eGFR) < 90 ml/min/m². Results In total, 125 CHB patients were matched 1:1 in both the cured and the uncured group. Renal function in the stage 1 and stage 2 groups showed a decreasing trend at 48 weeks after an initial increase. After PSM matching, the study included patients in the pegIFN-ETV or pegIFN-TDF group (n = 208, respectively), and 104 patients in the pegIFN-alone group. No significant difference in the impact of the three drug regimens on renal function at 48 weeks was found ( P = 0.955). A logistic regression model using age and baseline eGFR predicted the AUC of eGFR status at 48 weeks to be 0.851 (95% CI , 0.807, 0.895). Conclusions After 48 weeks of combined treatment in patients with CHB, neither pegIFN-TDF nor pegIFN-ETV led to an increase in renal injury. Renal function Interferon Combined treatment Chronic hepatitis B Monocentric Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction Chronic hepatitis B (CHB) is a significant global health issue, with 3.8% of the population infected with HBsAg in 2019. This has led to 1.5 million new infections, 296 million chronic cases, and 820,000 deaths from related liver diseases [ 1 ] . Antiviral therapy is the main treatment for CHB; however, it may not achieve HBsAg clearance, leading to lifelong treatment with drugs such as entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) [ 2 , 3 , 4 ] . The latest guidelines recommend ETV, TDF and TAF as first-line drugs for CHB treatment. TDF may cause renal and bone safety issues, including hypophosphatemia, renal dysfunction, and osteomalacia [ 5 ] . ETV has a good safety profile, with only 0.2% of patients experiencing serious adverse reactions in a 10-year global study [ 6 ] . Multiple studies have indicated that patients with low HBsAg levels and negative HBeAg before interferon (IFN) treatment are more likely to achieve clinical cure with sequential pegIFN treatment [ 7 , 8 , 9 ] . Guidelines advise against using TDF and recommend using ETV or TAF as the preferred anti-HBV drugs for patients who have kidney disease or who are receiving renal replacement therapy [ 10 , 11 ] . Compared with TDF, ETV is considered safer for the kidneys, making it the preferred choice for patients with reduced renal function [ 12 ] . Research on renal function in CHB patients treated with pegIFN and ETV revealed that the eGFR significantly improved within 48 weeks [ 13 ] . However, no study has compared the effects of pegIFN with those of ETV and TDF on kidney function in CHB patients. Therefore, this study compared renal function changes in patients treated with pegIFN combined with ETV or TDF. 2 Methods 2.1 Study population CHB patients treated with pegIFN or combined ETV and TDF between 2018 and 2020 were included in this retrospective study. All patients were part of a larger multicentre study conducted in China [ 14 ] . The study followed clinical guidelines and ethical standards and was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. 2.2 Data collection and follow-up Demographic, treatment, and laboratory data for patients with chronic hepatitis B (CHB) have been systematically collected from electronic medical records since the initiation of antiviral therapy (AVT). Patients were categorized into a cured group or a non-cured group based on HBsAg clearance at 48 weeks, though this classification does not represent the final treatment outcome as follow-up is ongoing. Renal function was assessed via estimated glomerular filtration rate (eGFR), serum phosphorus, and serum cystatin C. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation. Baseline measurements of these indices were taken at enrolment, with follow-up evaluations at weeks 0, 12, 24, 36, and 48 between 2018 and 2020. 2.3 Antiviral treatment Patients were treated from the outset with either pegylated interferon (pegIFN) alone or in combination with entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Clinical cure was defined as sustained hepatitis B surface antigen (HBsAg) loss after treatment cessation, with or without anti-HBs antibodies, undetectable hepatitis B virus (HBV) DNA, and normal liver enzyme levels. Serum hepatitis B e antigen (HBeAg) was semiquantified using commercial enzyme immunoassays on the Cobas e601 platform (Roche, Geneva, Switzerland), with results expressed as log10 cutoff index (COI). Plasma HBV DNA levels were quantified via real-time polymerase chain reaction (PCR) using the COBAS AmpliPrep-COBAS TaqMan HBV test (CAP-CTM; Roche Molecular Systems, Branchburg, USA), which has a lower detection limit of 20 IU/mL; results are reported as log10 IU/mL. Quantitative HBsAg (qHBsAg) concentrations in serum were measured with the Cobas e601 system (Roche, Geneva, Switzerland), which has a detection limit of 0.05 IU/mL, and are presented as log10 IU/mL. 2.4 Outcomes of renal function The research primarily found a slight decrease in the estimated glomerular filtration rate (eGFR) after 48 weeks. Liver and kidney functions were assessed using a biochemical analyzer, measuring serum alanine aminotransferase, blood creatinine, and blood urea nitrogen. According to the American Kidney Foundation's guidelines, an eGFR below 90 ml/min indicates decreased kidney function. This decrease, not meeting chronic kidney disease staging criteria, was labeled as early renal impairment. An eGFR under 90 ml/min/1.73 m² suggests mild kidney function reduction (stage 1), while 90 ml/min/1.73 m² or higher is normal (stage 2). 2.5 Statistical analysis Missing values in SPSS were imputed using the sequence average, resulting in two complete datasets. Baseline characteristics were compared across treatment groups via propensity score matching, applying a 1:1 ratio for cured versus uncured patients and a 2:2:1 ratio for patients receiving pegIFN alone, pegIFN with ETV, or pegIFN with TDF. Nearest-neighbour matching was performed with a calliper of 0.1 to ensure complete matching. Continuous variables are expressed as mean ± SD and interquartile range, while categorical variables are summarized as numbers and percentages. Multivariate and ROC curve analyses were employed to predict and evaluate renal function at 48 weeks. Binary mixed logistic regression was used to predict 48-week renal outcomes, with a significance threshold of P < 0.05. Analyses were conducted using IBM SPSS Statistics 27, GraphPad Prism 9, and web-based analysis tools. 3 Results 3.1 Baseline characteristics Based on the inclusion criteria established for the enrolled patients, a total of 625 patients diagnosed with CHB were selected for statistical analysis, comprising 278 individuals in the uncured group and 347 individuals in the cured group (Figure 1). The baseline characteristics of the patients are presented in Table 1. Prior to matching, the average age of patients with CHB in the uncured group was notably higher (43.3 years vs. 39.1 years, P < 0.001). After matching, there were no statistically significant differences in the average age or sex ratio between the CHB patients in the uncured group and those in the cured group ( P = 0.479, P = 0.054). Additionally, there were no statistically significant differences in the treatment regimen or baseline HBsAg level between the two groups ( P = 0.513, P = 0.492). Moreover, there was no statistically significant difference in baseline renal function between the two groups of CHB patients, as indicated by the estimated glomerular filtration rate (eGFR) and the inorganic phosphorus (IPHOS) and cystatin C (CysC) levels (all P > 0.05). Table1. Baseline characteristics of participants before and after propensity score matching. Baseline Characteristics Before PSM ( N=625 ) P Value After PSM ( N=250 ) P Value Uncured Cured (N=278) (N=347) Uncured Cured (N=125) (N=125) Age (years) 43.35±8.66 39.15±8.52 ＜0.001 41.38±9.33 41.75±8.65 0.479 Sex male 23 57 ＜0.001 113 110 0.054 female Treatment The types of NAs in combination therapy ETV TDF TAF Other NAs Peg-IFN (num.) Blood routine 255 135 (49%) 110 (40%) 20 (7%) 13 (4%) 53 (48-60) 290 162 (47%) 149 (43%) 15 (4%) 21 (6%) 45 (48-52) 0.341 12 60 (48%) 110 (40%) 8 (6%) 5 (4%) 49 (37-60) 15 57 (46%) 149 (43%) 14 (10%) 7 (6%) 48 (3-60) 0.513 WBC (×10 9 /L) 6.13±1.48 5.88±1.56 0.058 6.07±1.33 5.87±1.56 0.291 HGB (g/L) 153.43±17.82 152.52±16.91 0.513 153.45±18.20 152.33±15.06 0.597 PLT (×10 9 /L) 206.74±52.77 208.80±58.96 0.649 209.08±49.65 206.28±58.26 0.291 LYM (×10 9 /L) 2.04±0.58 1.98±0.58 0.260 1.98±0.56 2.00±0.57 0.807 NEUT (×10 9 /L) 3.48±1.19 3.27±1.23 0.026 3.47±1.07 3.25±1.21 0.122 HBsAg (iu/ml) 751.01±643.79 243.58±283.47 ＜0.001 454.42±288.32 426.81±343.72 0.492 Blood biochemistry data AST (U/L) 31.52±18.67 31.07±25.92 0.811 29.82±16.17 32.54±31.26 0.388 ALT (U/L) 36.15±25.84 36.80±37.17 0.805 34.65±24.62 39.49±48.62 0.322 TBIL (µmol/L) 12.21±6.73 11.65±5.04 0.235 12.96±7.58 11.96±5.73 0.243 DBIL (µmol/L) 3.65±3.76 3.24±1.66 0.072 4.41±5.29 3.33±1.79 0.032 ALB (g/L) 47.58±3.18 48.20±2.74 0.010 47.84±3.20 48.24±2.66 0.280 eGFR(ml/min/1.73 m²) 101.64±14.70 104.64±16.11 0.016 103.07±14.18 102.70±16.10 0.850 IPHOS (mmol/L) 1.03±0.16 1.06±0.29 0.119 1.04±0.14 1.08±0.34 0.308 Cysc (mg/L) 0.90±0.14 0.87±0.14 0.005 0.89±0.12 0.88±0.13 0.564 Note : Continuous variables are expressed as the mean ± standard deviation (SD), and categorical variables are expressed as numbers and percentages (%). Abbreviations : WBC, white blood cell; HGB, haemoglobin; PLT, platelet count; Lym, lymphocyte count; Neut, neutrophil neutrophil count; HBsAg, hepatitis B surface antigen; Ast, aspartate aminotransferase; Alt, alanine aminotransferase; TBIL, total bilirubin serum total bilirubin; DBIL, direct bilirubin; ALB, albumin, albumin; eGFR, estimated glomerular filtration rate; IPHOS, iphos, serum inorganic phosphorus; CysC, Cystatin C, serum cystatin. a 1: One covariate in the matched model included age, total number of interferon needles, baseline HBsAg, baseline ALT, and baseline eGFR. b 2:Data conforming to a normal distribution were analysed for differences (Wilcoxon rank sum test and chi square test) using the two independent samples t test. 3.2 Renal function The eGFR of the study population, stratified by cure status, sex, and age, decreased at 12 weeks of treatment among women and patients under 40 years of age in the cured group. After 12 weeks of treatment, the eGFR in the uncured group decreased, whereas the eGFR in the cured group continuously increased until the 24-week mark（Figure2）,The trend of eGFR changes after 12 weeks of treatment appears to correlate well with the state of cure, which seems to be related to the patient's response to interferon, making it a key point worthy of further study. A statistically significant decrease was subsequently detected in both groups at the 48 weeks ( P < 0.05, Figure2). During the 48-week treatment period, women exhibited a greater eGFR than men did. Specifically, women exhibited an increase in the eGFR at 36 weeks, while men continued to experience a decrease. The difference between the two groups was found to be statistically significant at 48 weeks ( P < 0.001, Figure2). After initially decreasing from 0 to 12 weeks in the cured state, the IPHOS levels increased according to sex and age group. CysC levels increased up to 36 weeks and then decreased in both groups, with no significant difference between them. CysC levels were greater in males older than 40 years than in the other groups at 48 weeks ( P < 0.05,Figure2 ). 3.3 Renal function after various treatment regimens There were no statistically significant differences in the age or sex distributions among patients receiving pegIFN in combination with ETV, pegIFN in combination with TDF, or pegIFN monotherapy. The analysis of eGFR levels indicated that the three treatment regimens exhibited similar patterns of change over the 48 weeks treatment period, with no statistically significant differences observed (all P > 0.05,Table2). Similarly, the levels of IPHOS demonstrated consistent trends among the three treatment groups throughout the 48 weeks treatment duration, with no statistically significant differences at 0, 12, 24, or 36 weeks (all P > 0.05,Table2). However, a statistically significant difference was noted at the 48 weeks mark ( P = 0.013,Table2,). The levels of CysC indicated that the three treatment regimens exhibited a consistent pattern of change over a 48 weeks treatment period, with no statistically significant differences observed at 0, 12, 24, or 48 weeks (all P > 0.05,Table2). However, a significant difference was noted at 36 weeks ( P = 0.029,Table2). Table2. Participant baseline characteristics after propensity score matching. Baseline Characteristics peg IFN-ETV （ N=208 ） peg IFN-TDF （ N=208 ） peg IFN alone （ N=104 ） P value Age（years） 36.1±9.1 35.3±9.2 36.6±8.8 0.462 Sex 0.955 male 176 178 89 female 32 30 15 Peg-IFN(num.) 47(36-60) 47(36-59) 51(38-60) 0.261 HBsAg（iu/ml） 0 w 418.33±366.09 444.98±477.61 344.93±295.55 0.117 12 w 278.93±374.78 329.81±469.90 245.42±332.25 0.188 24 w 170.05±300.37 207.46±360.38 192.31±345.52 0.520 36 w 134.71±260.41 168.98±330.66 288.64±1515.15 0.205 48 w 131.54±238.79 174.70±495.13 122.08±225.05 0.353 Biochemistry data（renal function） eGFR（ml/min/1.73 m²） 0 w 103.44±14.74 104.34±16.03 106.97±15.06 0.156 12 w 107.54±13.57 109.59±14.01 111.29±14.52 0.067 24 w 107.98±12.87 110.06±14.28 108.99±13.79 0.297 36 w 106.17±13.20 108.96±12.84 107.16±15.51 0.107 48 w 105.06±14.08 106.51±13.92 105.17±15.02 0.537 IPHOS（mmol/L） 0 w 1.04±2.67 1.05±0.18 1.08±0.33 0.384 12 w 1.00±0.26 1.05±0.39 1.00±0.23 0.258 24 w 1.02±0.20 1.05±0.33 1.06±0.30 0.466 36 w 1.07±0.20 1.08±0.16 1.09±0.35 0.641 48 w 1.09±0.15 1.11±0.15 1.05±0.18 0.013 CREAT(μmol/L) 0 w 80.50±14.22 74.93±14.33 68.31±15.08 ＜0.001 12 w 75.35±12.99 69.39±14.15 64.20±13.31 ＜0.001 24 w 75.31±12.50 69.53±13.70 64.09±13.78 ＜0.001 36 w 76.79±13.24 70.72±13.39 64.67±11.58 ＜0.001 48 w 80.07±14.05 72.81±17.89 64.58±13.45 ＜0.001 Cysc（mg/L） 0 w 0.87±0.13 0.88±0.14 0.85±0.16 0.304 12 w 0.97±0.16 0.95±0.16 0.94±0.16 0.191 24 w 1.01±0.16 1.01±0.16 1.00±0.19 0.875 36 w 1.03±0.17 1.00±0.15 0.98±0.20 0.029 48 w 1.01±0.78 0.99±0.16 1.00±0.17 0.373 Abbreviations : pegIFN-ETV, pegylated interferon entecavir, pegylated interferon combined with entecavir; pegIFN-TDF, pegylated interferon tenofovir disoproxil, pegylated interferon combined with tenofovir fumarate; pegIFN, pegylated interferon, pegylated interfero. 3.4 Variation tendencies at the different stages of renal function. Participants were divided into stage 1 and stage 2 groups based on their baseline renal function. The renal function in both groups increased and then decreased at 48 weeks, with higher eGFR in the pegIFN-TDF group than in the other two groups. There was no significant difference in renal function between the stage 1 and stage 2 groups; however, there was a significant difference in the eGFR at 12, 24, and 36 weeks in the stage 2 group (P < 0.05,Figure3).In addition, we also analyzed the changes in renal function among the three treatment regimens for the two staged patients, and the results showed that there was no significant difference in the changes in renal function among the three treatment regimens at 12, 24, 36 and 48 weeks（ F igureS3 ）. 3.5 Efficacy test of predictors for renal outcome Four factors were chosen for predictive testing based on LASSO regression and multivariate analysis（ FigureS4 ）. The first two factors, baseline eGFR and age, were selected using the AUC. Logistic regression was used to predict the eGFR at 48 weeks in patients. The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.851 (95% CI : 0.807, 0.895,Figure4 and Table3). At a prediction probability threshold of 0.853, the Youden index was maximized for patients with normal renal function at 48 weeks of treatment, yielding a sensitivity and specificity of 0.781 each. We created nomograms and analysed a calibration curve to evaluate the impact of sex, age, cure status, and eGFR on renal function after 48 weeks of treatment. The calibration curve had a C index of 0.729, indicating moderate accuracy. Table3. Age and Baseline Renal Function Indicators Predict 48-Week Renal Outcomes Variables AUC P value 95%Confidence interval Age 0.698 ＜0.001 0.630-0.765 eGFR0W 0.849 ＜0.001 0.807-0.891 IPHOS0W 0.596 0.009 0.525-0.666 Cysc0W Age-eGFR0W 0.659 0.851 ＜0.001 ＜0.001 0.591-0.727 0.807-0.895 4 Discussion The objective of this empirical investigation was to enhance the likelihood of clinical remission and prognosis for a greater number of individuals affected by CHB. By augmenting the remission rates of CHB and diminishing the population of hepatitis B carriers, this study underscores the imperative for the nation to mitigate "morbidity and mortality." The establishment of a substantial cohort receiving pegIFN treatment for CHB patients aims to identify optimal patient profiles and treatment protocols conducive to clinical remission through the analysis of extensive datasets, thereby facilitating their widespread implementation. Doctors' ability to treat CHB should be enhanced through specialized training. The present study, in specifically examining renal function injury, offers long-term renal function safety data regarding patients receiving pegIFN or oral antiviral drugs. These data are crucial for understanding the impact of drugs on renal function in clinical trials and cohort studies. Patients who were clinically cured at 48 weeks had better renal function than those who were not cured, indicating a better response to pegIFN and potential benefits in terms of renal function. This finding aligns with those of previous studies suggesting that pegIFN therapy may improve the eGFR in patients with CHB [13] . There was no notable difference in renal function outcomes after 48 weeks between patients treated with pegIFN combined with ETV and those treated with TDF, suggesting that oral antiviral drugs may be a suitable choice for CHB patients receiving combined pegIFN therapy. First-line nucleoside drugs are primarily excreted in urine, with TDF showing dose-dependent nephrotoxicity in both animal and human studies. TDF is a water-soluble diester prodrug of tenofovir with a diphenylfuroate group, but its poor stability and low utilization are due to its short half-life and inability to selectively decompose and release in the liver [15] . As TDF is taken for longer periods, the number of reported kidney side effects is increasing [16] . Koklu et al. reported that TDF is more effective at reducing the eGFR than other nucleoside drugs [17] . Observational studies suggest that TDF may increase the risk of renal function injury, especially in older or menopausal patients [18] . There is still debate about treating renal function with pegIFN alone or in combination with oral antiviral drugs. Numerous studies have demonstrated that pegIFN can enhance kidney function in patients with renal insufficiency and transplants [19,20,21,22] . The exact mechanism by which pegIFN protects the kidneys is still unknown. This study suggested that the high content and the shape of pegIFN may slow drug excretion in the kidneys, potentially protecting them. Studies have shown that lower levels of peripheral CD 4 CXCR 5 follicular helper T cells are linked to higher eGFRs, indicating a potential role in improving the eGFR through pegIFN [23] . There are limited studies on how pegIFN or combined oral antiviral drugs affect patients’ kidney function. Previous research revealed [24] no significant difference in the average eGFR between TDF and ETV in patients with normal renal function. However, in patients with moderate renal impairment, the average eGFR was lower in the TDF group and decreased during treatment. This study also revealed that viral inhibition could improve renal function to some extent, potentially explaining why combined treatments did not significantly affect renal function. Our study offers clinicians a more precise selection of antiviral drug regimens by using propensity score matching to balance patient characteristics. The findings from the observation of renal function in two groups, one of which was uncured and the other cured, undergoing a 48-week treatment with pegIFN combined with oral antiviral drugs indicated that the renal function of the cured group was superior to that of the uncured group.In addition, our study also analyzed the correlation analysis of ALT and eGFR levels in patients, and the results also revealed that with the emergence of ALT firelight eGFR levels appeared to be elevated, and more than suggestive of the relevance of the changes in eGFR in the biochemical response of the patients, and behind it may be due to the clearance of HBV in the patient's body( FigureS2 ). Furthermore, the similar change trend observed in both groups indirectly suggests a potential association between the response to pegIFN and renal function outcomes in patients. Subsequently, propensity score matching was employed to mitigate any imbalances in clinical characteristics among the three cohorts receiving pegIFN alone, pegIFN in combined with ETV, and pegIFN in combined with TDF. The study revealed no discernible differences in the impact of the three treatment protocols on renal function outcomes after a 48 weeks period. Furthermore, these findings suggest that TDF offers a wider range of treatment options for combination therapy than ETV or oral antiviral drugs alone. Additionally, the high quality of the study cohort allowed for the accurate prediction of renal function outcomes at 48 weeks. Age and baseline eGFR were identified as significant predictors for assessing renal outcomes, underscoring the importance for clinicians to promptly monitor renal function in older patients or those with poor baseline renal function.Then, our study also analyzed the healing status, age subgroups and gender of patients as well as renal function staging among the three treatment regimens, but no significant differences were seen, thus, our study further established our conclusion that there was no difference in the effect of ETV and TDF on renal function of patients over the combination of pegIFN ( TableS4,FigureS1 ). This study is subject to certain limitations. The disease type prevalent in the study cohort is predominantly singular, thus limiting its ability to accurately represent the complexities present in patients with renal complications. Additionally, the duration of observation in this study was relatively short, suggesting that further research with an extended observation period may be necessary for comprehensive validation. Declarations Authors’ contributions Z.Jh. and W.Ll. proposed the study. Z.Jh. W.Ll. and D.H designed the study. Z.Jh. and W.Ll.performed research and wrote the first draft manuscript. Z.Jh. W.Ll. and Y.Xa. collected and analyzed the data. D.H. and G.Zl.reviewed the draft manuscript and provided feedback. All authors read and approved the final manuscript. Acknowledgements We would like to thank the participants and staff of the Third Affiliated Hospital of Sun Yat-sen University for their valuable contributions. Funding information This work was supported by the National Natural Science Foundation of China, grant numbers 81870597 and 82170612, and the Guangzhou Science and Technology Program Key Projects, grant number 2023B01J1007. The funders had no role in the design or conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review or approval of the manuscript. Ethics declarations Due to the retrospective nature of the study, the need to obtain the informed consent was waived by the Full name of the IRB/ethical committee.The study protocol was consistent with the International Conference on Harmonization Guidelines, applicable regulations, and ethical guidelines of the Declaration of Helsinki. The protocol and consent forms were approved by the Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China ([2018]02-218-02). Patients receiving antiviral therapy were obtained from a real-world study registered at clinicaltrials.gov (chictr180020369). Data availablity The datasets analyzed during the current study are not publicly available due privacy reasons but are available from the author [email protected] on reasonable request. Consent for Publication Not applicable. Competing interests The authors declare that they have no competing interests. ORCID Jinhua Zhao https://orcid.org/0009-0008-1757-8841 Lili Wu https://orcid.org/0000-0002-1319-7274 References Global progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies 2016–2021. Actions for impact[EB/OL]; 2021. Peng CY, Chien RN. Liaw YF.Hepatitis B vrius-related decompensated liver cirrhosis:benefits of antiviral therapy. J Hepatol. 2012;57(2):442–50. Kim HS, Baatarkhuu O, Lee HW. Fibrosis-matched outcomes between chronic hepatitis B patients with drug-induced virological response and inactive carriers. Liver Int. 2019;39(1):81–9. Hosaka T, Suzuki F, Kobayashi M. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study. J Gastroenterol. 2013;48(8):930–41. 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Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. Transpl Int. 1998;11(Suppl 1):S135–9. Mederacke I, Yurdaydin C, Großhennig A, Hep-Net/International Delta Hepatitis Study Group, et al. Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection. J Viral Hepat. 2012;19(6):387–95. Zhang Y, Zhang WL, Pang XW, et al. Effect of 48-week pegylated interferon α-2a or nucleos(t)ide analogue therapy on renal function in Chinese patients with chronic hepatitis B. Virol J. 2017;14(1):49. Liu Y, Zhao P, Qu Z, et al. Frequency of CD4 + CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy. Int Immunopharmacol. 2014;22(1):98–106. Trinh S, Le AK, Chang ET, et al. Changes in Renal Function in Patients With Chronic HBV Infection Treated With Tenofovir Disoproxil Fumarate vs Entecavir. Clin Gastroenterol Hepatol. 2019;17(5):948–e9561. Epub 2018 Aug 18. PMID: 30130625. Additional Declarations No competing interests reported. Supplementary Files SupplementarymaterialTABLES1.docx SupplementarymaterialTABLES2.docx SupplementarymaterialTABLES4.docx SupplementarymaterialFIGURES3.docx SupplementarymaterialFIGURES4.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 09 Mar, 2026 Reviews received at journal 08 Mar, 2026 Reviews received at journal 04 Mar, 2026 Reviewers agreed at journal 28 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers agreed at journal 23 Feb, 2026 Reviewers invited by journal 17 Feb, 2026 Editor assigned by journal 17 Feb, 2026 Editor invited by journal 17 Feb, 2026 Submission checks completed at journal 16 Feb, 2026 First submitted to journal 16 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8719411","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":594362267,"identity":"466d7e0a-844d-4c5c-a740-d1e1e8162972","order_by":0,"name":"jinhua Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACfvbGhgMJFTVy9u3NB4jTItlzuPHBhzPHjA14jiUQp8XgRnqz4cw25sQNEjkGRLrszME2aZ4zbIzbJXI+3njDYCen20BAB2N7I1BLhQyzZc/bzZZzGJKNzQ4Q0MLMA7GFjeF47jZpHoYDidsIaWGTSGyT5m1jBirOeUacFh6JRLD3JQxO5LARp0WC5yA4kA0ke44ZW84xIMIv9sfbH4Cisr6fvfnhjTcVdnIEtaBZSWzUIGkhVccoGAWjYBSMCAAAOZpIp8bPhR0AAAAASUVORK5CYII=","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"jinhua","middleName":"","lastName":"Zhao","suffix":""},{"id":594362268,"identity":"04300d9c-a434-488c-8e47-2f426dcc3375","order_by":1,"name":"Wu Lili","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Wu","middleName":"","lastName":"Lili","suffix":""},{"id":594362269,"identity":"c5daba78-015a-46b0-a318-7e8864118227","order_by":2,"name":"Xiao an Yang","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"an","lastName":"Yang","suffix":""},{"id":594362270,"identity":"3f387c8a-5afb-40d6-8b90-118e4024b937","order_by":3,"name":"zhi liang Gao","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"zhi","middleName":"liang","lastName":"Gao","suffix":""},{"id":594362271,"identity":"ca026836-dbcd-4f82-a6c1-b6f70e606204","order_by":4,"name":"Hong Deng","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Deng","suffix":""}],"badges":[],"createdAt":"2026-01-28 10:39:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8719411/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8719411/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505291,"identity":"1938e835-ad75-4d63-b7e7-f97f68755cab","added_by":"auto","created_at":"2026-02-26 13:29:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57003,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study. PSM: propensity score matching.\u003cbr\u003e\n \u003cstrong\u003eNote\u003c/strong\u003e: The included covariates were age, total number of pegylated interferon needles, HBsAg, and eGFR0W.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/8cbc3b2be45cc65612338d4f.png"},{"id":103505197,"identity":"2061cc30-e903-4a0c-baf5-cd6a6d337f36","added_by":"auto","created_at":"2026-02-26 13:27:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":177570,"visible":true,"origin":"","legend":"\u003cp\u003eRenal function between different healing, sex and age groups. (A) Changes in the eGFR between different healing states. (B) Changes in eGFR between different sexes. (C) Changes in the eGFR at different ages (\u0026lt; 40 years, ≥ 40 years). (D) Changes in the IPHOS between different healing states. (E) Changes in IPHOS between different genders. (F) Changes in the IPHOS at different ages (\u0026lt; 40 years old, ≥ 40 years old). (G) Changes in CysC between different cure states. (H) Changes in CysC between different sexes. (I) Changes in CysC at different ages (\u0026lt; 40 years old, ≥ 40 years old). \u003csup\u003ens\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05, *\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05, **\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/06396ec40fe1b3387732f2e4.png"},{"id":103505167,"identity":"0f1fca2f-bd12-431a-a3de-cccc365efee0","added_by":"auto","created_at":"2026-02-26 13:25:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":162920,"visible":true,"origin":"","legend":"\u003cp\u003eVariation tendencies at the different stages of renal function.\u003c/p\u003e\n\u003cp\u003e(A). Variation tendency of eGFR at stage 1. (B). Variation tendency of IPHOS at stage 1. (C). Variation tendency of Cysc at stage 1. (D). Variation tendency of eGFR at stage 2. (E). Variation tendency of IPHOS at stage 2. (F). Variation tendency of Cysc at stage 2.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/bfbf8a8f6c172069d83d7b8a.png"},{"id":103216588,"identity":"68d934a5-26d5-4028-b298-12433841ade6","added_by":"auto","created_at":"2026-02-23 09:37:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":202231,"visible":true,"origin":"","legend":"\u003cp\u003eEfficacy test of predictors for renal outcome.\u003c/p\u003e\n\u003cp\u003e(A). ROC curve for predicting the renal outcome at 48 weeks of treatment.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/c50dced447f79e72235d4b83.png"},{"id":103509526,"identity":"e075f76a-04c3-4859-8b48-a7a339094c5c","added_by":"auto","created_at":"2026-02-26 13:59:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1406416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/0dc38aca-1622-4df0-8a98-d27e1cf8f605.pdf"},{"id":103505250,"identity":"93ef080a-34cb-4c98-a496-4682009ad36c","added_by":"auto","created_at":"2026-02-26 13:28:57","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15477,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialTABLES1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/e8143e7cb3ff8b18be72f692.docx"},{"id":103505298,"identity":"6c2833c9-b51b-4d87-8b8f-afb9226e6887","added_by":"auto","created_at":"2026-02-26 13:29:33","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15576,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialTABLES2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/dd4831303f425f25cd1de059.docx"},{"id":103216586,"identity":"50c97778-dcd2-49bf-8ab0-42e87867c581","added_by":"auto","created_at":"2026-02-23 09:37:03","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":12944,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialTABLES4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/f3d6524e34f2c2be95f5136c.docx"},{"id":103216587,"identity":"3c7fd132-b935-456f-8b8f-c4e674df1cfd","added_by":"auto","created_at":"2026-02-23 09:37:03","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":110765,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialFIGURES3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/ad9e31476ae347c428a71103.docx"},{"id":103216589,"identity":"57951442-5352-4e69-bd02-3f520af453b7","added_by":"auto","created_at":"2026-02-23 09:37:03","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":560256,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialFIGURES4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8719411/v1/b9d9571fed6a2be28a108794.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Changes in renal function and indicators in chronic hepatitis B patients undergoing antiviral therapy for 48 weeks: A prospective cohort study in China","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eChronic hepatitis B (CHB) is a significant global health issue, with 3.8% of the population infected with HBsAg in 2019. This has led to 1.5\u0026nbsp;million new infections, 296\u0026nbsp;million chronic cases, and 820,000 deaths from related liver diseases\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Antiviral therapy is the main treatment for CHB; however, it may not achieve HBsAg clearance, leading to lifelong treatment with drugs such as entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF)\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The latest guidelines recommend ETV, TDF and TAF as first-line drugs for CHB treatment. TDF may cause renal and bone safety issues, including hypophosphatemia, renal dysfunction, and osteomalacia\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. ETV has a good safety profile, with only 0.2% of patients experiencing serious adverse reactions in a 10-year global study\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Multiple studies have indicated that patients with low HBsAg levels and negative HBeAg before interferon (IFN) treatment are more likely to achieve clinical cure with sequential pegIFN treatment\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Guidelines advise against using TDF and recommend using ETV or TAF as the preferred anti-HBV drugs for patients who have kidney disease or who are receiving renal replacement therapy\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Compared with TDF, ETV is considered safer for the kidneys, making it the preferred choice for patients with reduced renal function\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Research on renal function in CHB patients treated with pegIFN and ETV revealed that the eGFR significantly improved within 48 weeks\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. However, no study has compared the effects of pegIFN with those of ETV and TDF on kidney function in CHB patients. Therefore, this study compared renal function changes in patients treated with pegIFN combined with ETV or TDF.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study population\u003c/h2\u003e \u003cp\u003eCHB patients treated with pegIFN or combined ETV and TDF between 2018 and 2020 were included in this retrospective study. All patients were part of a larger multicentre study conducted in China\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. The study followed clinical guidelines and ethical standards and was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection and follow-up\u003c/h2\u003e \u003cp\u003eDemographic, treatment, and laboratory data for patients with chronic hepatitis B (CHB) have been systematically collected from electronic medical records since the initiation of antiviral therapy (AVT). Patients were categorized into a cured group or a non-cured group based on HBsAg clearance at 48 weeks, though this classification does not represent the final treatment outcome as follow-up is ongoing. Renal function was assessed via estimated glomerular filtration rate (eGFR), serum phosphorus, and serum cystatin C. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation. Baseline measurements of these indices were taken at enrolment, with follow-up evaluations at weeks 0, 12, 24, 36, and 48 between 2018 and 2020.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Antiviral treatment\u003c/h2\u003e \u003cp\u003ePatients were treated from the outset with either pegylated interferon (pegIFN) alone or in combination with entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Clinical cure was defined as sustained hepatitis B surface antigen (HBsAg) loss after treatment cessation, with or without anti-HBs antibodies, undetectable hepatitis B virus (HBV) DNA, and normal liver enzyme levels. Serum hepatitis B e antigen (HBeAg) was semiquantified using commercial enzyme immunoassays on the Cobas e601 platform (Roche, Geneva, Switzerland), with results expressed as log10 cutoff index (COI). Plasma HBV DNA levels were quantified via real-time polymerase chain reaction (PCR) using the COBAS AmpliPrep-COBAS TaqMan HBV test (CAP-CTM; Roche Molecular Systems, Branchburg, USA), which has a lower detection limit of 20 IU/mL; results are reported as log10 IU/mL. Quantitative HBsAg (qHBsAg) concentrations in serum were measured with the Cobas e601 system (Roche, Geneva, Switzerland), which has a detection limit of 0.05 IU/mL, and are presented as log10 IU/mL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcomes of renal function\u003c/h2\u003e \u003cp\u003eThe research primarily found a slight decrease in the estimated glomerular filtration rate (eGFR) after 48 weeks. Liver and kidney functions were assessed using a biochemical analyzer, measuring serum alanine aminotransferase, blood creatinine, and blood urea nitrogen. According to the American Kidney Foundation's guidelines, an eGFR below 90 ml/min indicates decreased kidney function. This decrease, not meeting chronic kidney disease staging criteria, was labeled as early renal impairment. An eGFR under 90 ml/min/1.73 m\u0026sup2; suggests mild kidney function reduction (stage 1), while 90 ml/min/1.73 m\u0026sup2; or higher is normal (stage 2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eMissing values in SPSS were imputed using the sequence average, resulting in two complete datasets. Baseline characteristics were compared across treatment groups via propensity score matching, applying a 1:1 ratio for cured versus uncured patients and a 2:2:1 ratio for patients receiving pegIFN alone, pegIFN with ETV, or pegIFN with TDF. Nearest-neighbour matching was performed with a calliper of 0.1 to ensure complete matching. Continuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and interquartile range, while categorical variables are summarized as numbers and percentages. Multivariate and ROC curve analyses were employed to predict and evaluate renal function at 48 weeks. Binary mixed logistic regression was used to predict 48-week renal outcomes, with a significance threshold of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were conducted using IBM SPSS Statistics 27, GraphPad Prism 9, and web-based analysis tools.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003e3.1 Baseline characteristics\u003c/p\u003e\n\u003cp\u003eBased on the inclusion criteria established for the enrolled patients, a total of 625 patients diagnosed with CHB were selected for statistical analysis, comprising 278 individuals in the uncured group and 347 individuals in the cured group (Figure 1). The baseline characteristics of the patients are presented in Table 1. Prior to matching, the average age of patients with CHB in the uncured group was notably higher (43.3 years vs. 39.1 years, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). After matching, there were no statistically significant differences in the average age or sex ratio between the CHB patients in the uncured group and those in the cured group (\u003cem\u003eP\u003c/em\u003e = 0.479, \u003cem\u003eP\u003c/em\u003e = 0.054). Additionally, there were no statistically significant differences in the treatment regimen or baseline HBsAg level between the two groups (\u003cem\u003eP\u003c/em\u003e = 0.513, \u003cem\u003eP\u003c/em\u003e = 0.492). Moreover, there was no statistically significant difference in baseline renal function between the two groups of CHB patients, as indicated by the estimated glomerular filtration rate (eGFR) and the inorganic phosphorus (IPHOS) and cystatin C (CysC) levels (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eTable1. Baseline characteristics of participants before and after propensity score matching.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore PSM\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eN=625\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;P\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter PSM\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eN=250\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" rowspan=\"2\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;P\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003eUncured \u0026nbsp; Cured\u003c/p\u003e\n \u003cp\u003e(N=278) \u0026nbsp; \u0026nbsp; \u0026nbsp;(N=347)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003eUncured \u0026nbsp; Cured\u003c/p\u003e\n \u003cp\u003e(N=125) \u0026nbsp; \u0026nbsp; \u0026nbsp;(N=125)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e43.35\u0026plusmn;8.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e39.15\u0026plusmn;8.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e41.38\u0026plusmn;9.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e41.75\u0026plusmn;8.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003cp\u003eThe types of NAs in combination therapy\u003c/p\u003e\n \u003cp\u003eETV\u003c/p\u003e\n \u003cp\u003eTDF\u003c/p\u003e\n \u003cp\u003eTAF\u003c/p\u003e\n \u003cp\u003eOther NAs\u003c/p\u003e\n \u003cp\u003ePeg-IFN (num.)\u003c/p\u003e\n \u003cp\u003eBlood routine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e255\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e135 (49%)\u003c/p\u003e\n \u003cp\u003e110 (40%)\u003c/p\u003e\n \u003cp\u003e20 (7%)\u003c/p\u003e\n \u003cp\u003e13 (4%)\u003c/p\u003e\n \u003cp\u003e53 (48-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e290\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e162 (47%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;149 (43%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;15 (4%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;21 (6%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;45 (48-52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60 (48%)\u003c/p\u003e\n \u003cp\u003e110 (40%)\u003c/p\u003e\n \u003cp\u003e8 (6%)\u003c/p\u003e\n \u003cp\u003e5 (4%)\u003c/p\u003e\n \u003cp\u003e49 (37-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e57 (46%)\u003c/p\u003e\n \u003cp\u003e149 (43%)\u003c/p\u003e\n \u003cp\u003e14 (10%)\u003c/p\u003e\n \u003cp\u003e7 (6%)\u003c/p\u003e\n \u003cp\u003e48 (3-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e6.13\u0026plusmn;1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e5.88\u0026plusmn;1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e6.07\u0026plusmn;1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e5.87\u0026plusmn;1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHGB (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e153.43\u0026plusmn;17.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e152.52\u0026plusmn;16.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e153.45\u0026plusmn;18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e152.33\u0026plusmn;15.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;0.597\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003ePLT (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e206.74\u0026plusmn;52.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e208.80\u0026plusmn;58.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.649\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e209.08\u0026plusmn;49.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e206.28\u0026plusmn;58.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eLYM (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e2.04\u0026plusmn;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e1.98\u0026plusmn;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.98\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e2.00\u0026plusmn;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNEUT (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e3.48\u0026plusmn;1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e3.27\u0026plusmn;1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e3.47\u0026plusmn;1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e3.25\u0026plusmn;1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHBsAg (iu/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e751.01\u0026plusmn;643.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e243.58\u0026plusmn;283.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e454.42\u0026plusmn;288.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e426.81\u0026plusmn;343.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eBlood biochemistry data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eAST (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e31.52\u0026plusmn;18.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e31.07\u0026plusmn;25.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e29.82\u0026plusmn;16.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e32.54\u0026plusmn;31.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eALT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e36.15\u0026plusmn;25.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e36.80\u0026plusmn;37.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e34.65\u0026plusmn;24.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e39.49\u0026plusmn;48.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eTBIL (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e12.21\u0026plusmn;6.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e11.65\u0026plusmn;5.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e12.96\u0026plusmn;7.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e11.96\u0026plusmn;5.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eDBIL (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e3.65\u0026plusmn;3.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e3.24\u0026plusmn;1.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e4.41\u0026plusmn;5.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e3.33\u0026plusmn;1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eALB (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e47.58\u0026plusmn;3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e48.20\u0026plusmn;2.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e47.84\u0026plusmn;3.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e48.24\u0026plusmn;2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eeGFR(ml/min/1.73 m\u0026sup2;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e101.64\u0026plusmn;14.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e104.64\u0026plusmn;16.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e103.07\u0026plusmn;14.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e102.70\u0026plusmn;16.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIPHOS (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e1.03\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e1.06\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.04\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e1.08\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eCysc (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.90\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.87\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.89\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.88\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e:\u0026nbsp;Continuous variables are expressed as the mean \u0026plusmn; standard deviation (SD), and categorical variables are expressed as numbers and percentages (%).\u003cbr\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: WBC, white blood cell; HGB, haemoglobin; PLT, platelet count; Lym, lymphocyte count; Neut, neutrophil neutrophil count; HBsAg, hepatitis B surface antigen; Ast, aspartate aminotransferase; Alt, alanine aminotransferase; TBIL, total bilirubin serum total bilirubin; DBIL, direct bilirubin; ALB, albumin, albumin; eGFR, estimated glomerular filtration rate; IPHOS, iphos, serum inorganic phosphorus; CysC, Cystatin C, serum cystatin.\u0026nbsp;\u003cbr\u003e\u003csup\u003ea\u003c/sup\u003e1: One covariate in the matched model included age, total number of interferon needles, baseline HBsAg, baseline ALT, and baseline eGFR.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e2:Data conforming to a normal distribution were analysed for differences (Wilcoxon rank sum test and chi square test) using the two independent samples t test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.2 Renal function\u003c/p\u003e\n\u003cp\u003eThe eGFR of the study population, stratified by cure status, sex, and age, decreased at 12 weeks of treatment among women and patients under 40 years of age in the cured group. After 12 weeks of treatment, the eGFR in the uncured group decreased, whereas the eGFR in the cured group continuously increased until the 24-week mark（Figure2）,The trend of eGFR changes after 12 weeks of treatment appears to correlate well with the state of cure, which seems to be related to the patient\u0026apos;s response to interferon, making it a key point worthy of further study. A statistically significant decrease was subsequently detected in both groups at the 48 weeks (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, Figure2). During the 48-week treatment period, women exhibited a greater eGFR than men did. Specifically, women exhibited an increase in the eGFR at 36 weeks, while men continued to experience a decrease. The difference between the two groups was found to be statistically significant at 48 weeks (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, Figure2). After initially decreasing from 0 to 12 weeks in the cured state, the IPHOS levels increased according to sex and age group. CysC levels increased up to 36 weeks and then decreased in both groups, with no significant difference between them. CysC levels were greater in males older than 40 years than in the other groups at 48 weeks (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05,Figure2 ).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e3.3 Renal function after various treatment regimens\u003c/p\u003e\n\u003cp\u003eThere were no statistically significant differences in the age or sex distributions among patients receiving pegIFN in combination with ETV, pegIFN in combination with TDF, or pegIFN monotherapy. The analysis of eGFR levels indicated that the three treatment regimens exhibited similar patterns of change over the 48 weeks treatment period, with no statistically significant differences observed (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05,Table2). Similarly, the levels of IPHOS demonstrated consistent trends among the three treatment groups throughout the 48 weeks treatment duration, with no statistically significant differences at 0, 12, 24, or 36 weeks (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05,Table2). However, a statistically significant difference was noted at the 48 weeks mark (\u003cem\u003eP\u003c/em\u003e = 0.013,Table2,). The levels of CysC indicated that the three treatment regimens exhibited a consistent pattern of change over a 48 weeks treatment period, with no statistically significant differences observed at 0, 12, 24, or 48 weeks (all \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05,Table2). However, a significant difference was noted at 36 weeks (\u003cem\u003eP\u003c/em\u003e = 0.029,Table2).\u003c/p\u003e\n\u003cp\u003eTable2. Participant baseline characteristics after propensity score matching.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epeg\u003c/strong\u003e\u003cstrong\u003eIFN-ETV\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eN=208\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epeg\u003c/strong\u003e\u003cstrong\u003eIFN-TDF\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eN=208\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003epeg\u003c/strong\u003e\u003cstrong\u003eIFN alone\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eN=104\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eAge（years）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e36.1\u0026plusmn;9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e35.3\u0026plusmn;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e36.6\u0026plusmn;8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.955\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePeg-IFN(num.)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e47(36-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e47(36-59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e51(38-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHBsAg（iu/ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e418.33\u0026plusmn;366.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e444.98\u0026plusmn;477.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e344.93\u0026plusmn;295.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e278.93\u0026plusmn;374.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e329.81\u0026plusmn;469.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e245.42\u0026plusmn;332.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e170.05\u0026plusmn;300.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e207.46\u0026plusmn;360.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e192.31\u0026plusmn;345.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e134.71\u0026plusmn;260.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e168.98\u0026plusmn;330.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e288.64\u0026plusmn;1515.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e131.54\u0026plusmn;238.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e174.70\u0026plusmn;495.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e122.08\u0026plusmn;225.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBiochemistry data（renal function）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eeGFR（ml/min/1.73 m\u0026sup2;）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e103.44\u0026plusmn;14.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e104.34\u0026plusmn;16.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e106.97\u0026plusmn;15.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e107.54\u0026plusmn;13.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e109.59\u0026plusmn;14.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e111.29\u0026plusmn;14.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e107.98\u0026plusmn;12.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e110.06\u0026plusmn;14.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e108.99\u0026plusmn;13.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e106.17\u0026plusmn;13.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e108.96\u0026plusmn;12.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e107.16\u0026plusmn;15.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e105.06\u0026plusmn;14.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e106.51\u0026plusmn;13.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e105.17\u0026plusmn;15.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIPHOS（mmol/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.04\u0026plusmn;2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.08\u0026plusmn;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.02\u0026plusmn;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.06\u0026plusmn;0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.07\u0026plusmn;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.08\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.09\u0026plusmn;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.641\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.09\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.11\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eCREAT(\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e80.50\u0026plusmn;14.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e74.93\u0026plusmn;14.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e68.31\u0026plusmn;15.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e75.35\u0026plusmn;12.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e69.39\u0026plusmn;14.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e64.20\u0026plusmn;13.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e75.31\u0026plusmn;12.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e69.53\u0026plusmn;13.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e64.09\u0026plusmn;13.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e76.79\u0026plusmn;13.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e70.72\u0026plusmn;13.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e64.67\u0026plusmn;11.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e80.07\u0026plusmn;14.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e72.81\u0026plusmn;17.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e64.58\u0026plusmn;13.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eCysc（mg/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.87\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.88\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.85\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.97\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.95\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.94\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.01\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.01\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e36 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.03\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.98\u0026plusmn;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e48 w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.01\u0026plusmn;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.99\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.00\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.373\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e:\u0026nbsp;pegIFN-ETV, pegylated interferon entecavir, pegylated interferon combined with entecavir;\u0026nbsp;pegIFN-TDF, pegylated interferon tenofovir disoproxil, pegylated interferon combined with tenofovir fumarate;\u0026nbsp;pegIFN, pegylated interferon, pegylated interfero.\u003c/p\u003e\n\u003cp\u003e3.4 Variation tendencies at the different stages of renal function.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants were divided into stage 1 and stage 2 groups based on their baseline renal function. The renal function in both groups increased and then decreased at 48 weeks, with higher eGFR in the pegIFN-TDF group than in the other two groups. There was no significant difference in renal function between the stage 1 and stage 2 groups; however, there was a significant difference in the eGFR at 12, 24, and 36 weeks in the stage 2 group (P \u0026lt; 0.05,Figure3).In addition, we also analyzed the changes in renal function among the three treatment regimens for the two staged patients, and the results showed that there was no significant difference in the changes in renal function among the three treatment regimens at 12, 24, 36 and 48 weeks（\u003cem\u003eF\u003c/em\u003e\u003cem\u003eigureS3\u003c/em\u003e）.\u003c/p\u003e\n\u003cp\u003e3.5 Efficacy test of predictors for renal outcome\u003c/p\u003e\n\u003cp\u003eFour factors were chosen for predictive testing based on LASSO regression and multivariate analysis（\u003cem\u003eFigureS4\u003c/em\u003e）. The first two factors, baseline eGFR and age, were selected using the AUC. Logistic regression was used to predict the eGFR at 48 weeks in patients. The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.851 (95% \u003cem\u003eCI\u003c/em\u003e: 0.807, 0.895,Figure4 and Table3). At a prediction probability threshold of 0.853, the Youden index was maximized for patients with normal renal function at 48 weeks of treatment, yielding a sensitivity and specificity of 0.781 each. We created nomograms and analysed a calibration curve to evaluate the impact of sex, age, cure status, and eGFR on renal function after 48 weeks of treatment. The calibration curve had a \u003cem\u003eC\u003c/em\u003e index of 0.729, indicating moderate accuracy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable3. Age and Baseline Renal Function Indicators Predict 48-Week Renal Outcomes\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%Confidence interval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.698\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.630-0.765\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eeGFR0W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.807-0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eIPHOS0W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.525-0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCysc0W\u003c/p\u003e\n \u003cp\u003eAge-eGFR0W\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.659\u003c/p\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.591-0.727\u003c/p\u003e\n \u003cp\u003e0.807-0.895\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThe objective of this empirical investigation was to enhance the likelihood of clinical remission and prognosis for a greater number of individuals affected by CHB. By augmenting the remission rates of CHB and diminishing the population of hepatitis B carriers, this study underscores the imperative for the nation to mitigate \"morbidity and mortality.\" The establishment of a substantial cohort receiving pegIFN treatment for CHB patients aims to identify optimal patient profiles and treatment protocols conducive to clinical remission through the analysis of extensive datasets, thereby facilitating their widespread implementation. Doctors' ability to treat CHB should be enhanced through specialized training. The present study, in specifically examining renal function injury, offers long-term renal function safety data regarding patients receiving pegIFN or oral antiviral drugs. These data are crucial for understanding the impact of drugs on renal function in clinical trials and cohort studies. Patients who were clinically cured at 48 weeks had better renal function than those who were not cured, indicating a better response to pegIFN and potential benefits in terms of renal function. This finding aligns with those of previous studies suggesting that pegIFN therapy may improve the eGFR in patients with CHB \u003csup\u003e[13]\u003c/sup\u003e. There was no notable difference in renal function outcomes after 48 weeks between patients treated with pegIFN combined with ETV and those treated with TDF, suggesting that oral antiviral drugs may be a suitable choice for CHB patients receiving combined pegIFN therapy. First-line nucleoside drugs are primarily excreted in urine, with TDF showing dose-dependent nephrotoxicity in both animal and human studies. TDF is a water-soluble diester prodrug of tenofovir with a diphenylfuroate group, but its poor stability and low utilization are due to its short half-life and inability to selectively decompose and release in the liver\u003csup\u003e[15]\u003c/sup\u003e. As TDF is taken for longer periods, the number of reported kidney side effects is increasing\u003csup\u003e[16]\u003c/sup\u003e. Koklu et al. reported that TDF is more effective at reducing the eGFR than other nucleoside drugs\u003csup\u003e[17]\u003c/sup\u003e. Observational studies suggest that TDF may increase the risk of renal function injury, especially in older or menopausal patients\u003csup\u003e[18]\u003c/sup\u003e. There is still debate about treating renal function with\u0026nbsp;pegIFN alone or in combination with oral antiviral drugs.\u003c/p\u003e\n\u003cp\u003eNumerous studies have demonstrated that pegIFN can enhance kidney function in patients with renal insufficiency and transplants\u003csup\u003e[19,20,21,22]\u003c/sup\u003e. The exact mechanism by which pegIFN protects the kidneys is still unknown. This study suggested that the high content and the shape of pegIFN may slow drug excretion in the kidneys, potentially protecting them. Studies have shown that lower levels of peripheral CD\u003csup\u003e4\u003c/sup\u003eCXCR\u003csup\u003e5\u003c/sup\u003e follicular helper T cells are linked to higher eGFRs, indicating a potential role in improving the eGFR through pegIFN\u003csup\u003e[23]\u003c/sup\u003e. There are limited studies on how pegIFN or combined oral antiviral drugs affect patients’ kidney function. Previous research revealed\u003csup\u003e[24]\u003c/sup\u003e no significant difference in the average eGFR between TDF and ETV in patients with normal renal function. However, in patients with moderate renal impairment, the average eGFR was lower in the TDF group and decreased during treatment. This study also revealed that viral inhibition could improve renal function to some extent, potentially explaining why combined treatments did not significantly affect renal function.\u003c/p\u003e\n\u003cp\u003eOur study offers clinicians a more precise selection of antiviral drug regimens by using propensity score matching to balance patient characteristics. The findings from the observation of renal function in two groups, one of which was uncured and the other cured, undergoing a 48-week treatment with pegIFN combined with oral antiviral drugs indicated that the renal function of the cured group was superior to that of the uncured group.In addition, our study also analyzed the correlation analysis of ALT and eGFR levels in patients, and the results also revealed that with the emergence of ALT firelight eGFR levels appeared to be elevated, and more than suggestive of the relevance of the changes in eGFR in the biochemical response of the patients, and behind it may be due to the clearance of HBV in the patient's body(\u003cem\u003eFigureS2\u003c/em\u003e). Furthermore, the similar change trend observed in both groups indirectly suggests a potential association between the response to pegIFN and renal function outcomes in patients.\u003c/p\u003e\n\u003cp\u003eSubsequently, propensity score matching was employed to mitigate any imbalances in clinical characteristics among the three cohorts receiving pegIFN alone, pegIFN in combined with ETV, and pegIFN in combined with TDF. The study revealed no discernible differences in the impact of the three treatment protocols on renal function outcomes after a 48 weeks period. Furthermore, these findings suggest that TDF offers a wider range of treatment options for combination therapy than ETV or oral antiviral drugs alone. Additionally, the high quality of the study cohort allowed for the accurate prediction of renal function outcomes at 48 weeks. Age and baseline eGFR were identified as significant predictors for assessing renal outcomes, underscoring the importance for clinicians to promptly monitor renal function in older patients or those with poor baseline renal function.Then, our study also analyzed the healing status, age subgroups and gender of patients as well as renal function staging among the three treatment regimens, but no significant differences were seen, thus, our study further established our conclusion that there was no difference in the effect of ETV and TDF on renal function of patients over the combination of pegIFN (\u003cem\u003eTableS4,FigureS1\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eThis study is subject to certain limitations. The disease type prevalent in the study cohort is predominantly singular, thus limiting its ability to accurately represent the complexities present in patients with renal complications. Additionally, the duration of observation in this study was relatively short, suggesting that further research with an extended observation period may be necessary for comprehensive validation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eZ.Jh. and W.Ll. proposed the study. Z.Jh. \u0026nbsp; W.Ll. and D.H designed the study. Z.Jh. and W.Ll.performed research and wrote the first draft manuscript. \u0026nbsp;Z.Jh. \u0026nbsp;W.Ll. and Y.Xa. collected and analyzed the data. \u0026nbsp;D.H. and G.Zl.reviewed the draft manuscript and provided feedback. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe would like to thank the participants and staff of the Third Affiliated Hospital of Sun Yat-sen University for their valuable contributions.\u003c/p\u003e\n\u003cp\u003eFunding information\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China, grant numbers 81870597 and 82170612, and the Guangzhou Science and Technology Program Key Projects, grant number 2023B01J1007. The funders had no role in the design or conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review or approval of the manuscript.\u003c/p\u003e\n\u003cp\u003eEthics declarations\u003c/p\u003e\n\u003cp\u003eDue to the retrospective nature of the study, the need to obtain the informed consent was waived by the Full name of the IRB/ethical committee.The study protocol was consistent with the International Conference on Harmonization Guidelines, applicable regulations, and ethical guidelines of the Declaration of Helsinki. The protocol and consent forms were approved by the Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China ([2018]02-218-02). Patients receiving antiviral therapy were obtained from a real-world study registered at clinicaltrials.gov (chictr180020369).\u003c/p\u003e\n\u003cp\u003eData availablity\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are not publicly available due privacy reasons but are available from the author [email protected] on reasonable request.\u003c/p\u003e\n\u003cp\u003eConsent for Publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eORCID\u003c/p\u003e\n\u003cp\u003eJinhua Zhao https://orcid.org/0009-0008-1757-8841\u003c/p\u003e\n\u003cp\u003eLili Wu https://orcid.org/0000-0002-1319-7274\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies 2016\u0026ndash;2021. Actions for impact[EB/OL]; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng CY, Chien RN. Liaw YF.Hepatitis B vrius-related decompensated liver cirrhosis:benefits of antiviral therapy. J Hepatol. 2012;57(2):442\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HS, Baatarkhuu O, Lee HW. Fibrosis-matched outcomes between chronic hepatitis B patients with drug-induced virological response and inactive carriers. Liver Int. 2019;39(1):81\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHosaka T, Suzuki F, Kobayashi M. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study. J Gastroenterol. 2013;48(8):930\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcellin P, Gane E, Buti M, et al. Regression of cirrhosis during hepatitis B: A 5-year open-label follow-up study[J]. Lancet. 2013;381(9865):468\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou JL, Zhao W, Lee C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries[J]. Clin Gastroenterol Hepatol. 2020;18(2):457\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNing Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial)[J]. J Hepatol. 2014;61(4):777\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan M, Jiang J, Hou J, et al. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-α2a: 1 year follow-up of the OSST study[J]. Antivir Ther. 2016;21(4):337\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu P, Shang J, Zhang W, et al. HBsAg loss with peg-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)ide analog: New switch study[J]. J Clin Transl Hepatol. 2018;6(1):25\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal K, Brunetto M, Seto WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection[J]. J Hepatol. 2018;68(4):672\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrossi G, Loglio A, Facchettif F, et al. Tenofovir alafenamide as a rescue therapy in a patient with HBV-cirrhosis with a history of Fanconi syndrome and multidrug resistance[J]. J Hepatol. 2018;68(1):195\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong GL-H, Chan HL-Y, Tse Y-K, et al. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir,entecavir,or no treatment. Aliment Pharmacol Ther. 2018;48:984\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng MJ, Guo XQ, Zhang WL, et al. Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience. Front Microbiol. 2022;13:980250.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu JH, Huang Y, Xie DY, et al. Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients. J Viral Hepat. 2022;29(9):765\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang E, Lee JK, Inn KS et al. Renal Dysfuncion and tubulopathy inducted by high-dose tenofovir disoproxil fumarate in C57BL/6 Mice.Healthcare.2020.8(4):417.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang X, Gao Z, Xie Q, et al. Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results. Hepatol Int. 2019;13:260\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoklu S, Gulsen MT, Tuna Y et al. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther, 41: 310\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiquilena-Colina ME, Lozano-Rodr\u0026iacute;guez T, Garc\u0026iacute;a-Pozo L, et al. Recombinant interferon-alpha2b improves immune response to hepatitis B vaccination in haemodialysis patients: results of a randomised clinical trial. Vaccine. 2009;27(41):5654\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurlik M, Gaciong Z, Rowińska D, et al. Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. Transpl Int. 1998;11(Suppl 1):S135\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMederacke I, Yurdaydin C, Gro\u0026szlig;hennig A, Hep-Net/International Delta Hepatitis Study Group, et al. Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection. J Viral Hepat. 2012;19(6):387\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Zhang WL, Pang XW, et al. Effect of 48-week pegylated interferon α-2a or nucleos(t)ide analogue therapy on renal function in Chinese patients with chronic hepatitis B. Virol J. 2017;14(1):49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Zhao P, Qu Z, et al. Frequency of CD4\u0026thinsp;+\u0026thinsp;CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy. Int Immunopharmacol. 2014;22(1):98\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrinh S, Le AK, Chang ET, et al. Changes in Renal Function in Patients With Chronic HBV Infection Treated With Tenofovir Disoproxil Fumarate vs Entecavir. Clin Gastroenterol Hepatol. 2019;17(5):948\u0026ndash;e9561. Epub 2018 Aug 18. PMID: 30130625.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Renal function, Interferon, Combined treatment, Chronic hepatitis B, Monocentric","lastPublishedDoi":"10.21203/rs.3.rs-8719411/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8719411/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThere is limited research comparing the renal safety of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) when used with pegylated interferon (pegIFN) in patients with chronic hepatitis B (CHB). Here, renal function changes in CHB patients were compared between treated with pegyIFN combined with ETV or TDF.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e713 patients with the combination therapy of pegIFN with ETV or TDF were included in a matched analysis comparing outcomes between cured (HBsAg\u0026thinsp;\u0026lt;\u0026thinsp;0.05IU/mL) and uncured patients, while 104 patients received pegIFN alone as a control group for comparison with the pegIFN-ETV and pegIFN-TDF treatment groups. The primary outcome was the change in renal function. Patients were categorized into stage 1 or stage 2 based on baseline estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;90 ml/min/m\u0026sup2;.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn total, 125 CHB patients were matched 1:1 in both the cured and the uncured group. Renal function in the stage 1 and stage 2 groups showed a decreasing trend at 48 weeks after an initial increase. After PSM matching, the study included patients in the pegIFN-ETV or pegIFN-TDF group (n\u0026thinsp;=\u0026thinsp;208, respectively), and 104 patients in the pegIFN-alone group. No significant difference in the impact of the three drug regimens on renal function at 48 weeks was found (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.955). A logistic regression model using age and baseline eGFR predicted the AUC of eGFR status at 48 weeks to be 0.851 (95% \u003cem\u003eCI\u003c/em\u003e, 0.807, 0.895).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAfter 48 weeks of combined treatment in patients with CHB, neither pegIFN-TDF nor pegIFN-ETV led to an increase in renal injury.\u003c/p\u003e","manuscriptTitle":"Changes in renal function and indicators in chronic hepatitis B patients undergoing antiviral therapy for 48 weeks: A prospective cohort study in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 09:36:58","doi":"10.21203/rs.3.rs-8719411/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-10T01:19:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-08T15:08:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-04T11:46:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215132730507173953486378284514685821497","date":"2026-02-28T18:55:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188910112552832769588842250900860892259","date":"2026-02-26T10:10:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270820974045926295189674754795086503037","date":"2026-02-23T16:57:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-17T12:38:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-17T12:34:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-17T11:50:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-16T15:37:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-02-16T15:34:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"10939316-1065-4446-9e81-e59a11ef194e","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-10T01:24:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 09:36:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8719411","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8719411","identity":"rs-8719411","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}