Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and HCV infection

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However, there is a lack of studies to report the effectiveness and safety of rituximab in patients with PLA2R associated MN and Hepatitis C virus (HCV) infection, which is the aim of this study. Methods: We performed a single center retrospective review of 8 consecutive PLA2R associated MN patients with HCV infection. We assessed clinical and laboratory indices, remission rates, and adverse events at rituximab infusion, month 6, month 12, and last visit. Results: A total of 8 patients were enrolled, with a median follow-up period of 19.00 (16.00, 25.25) months. Of the 8 patients, 5 were male, and mean age was 50.13±4.29 years. At last visit, 5 (62.50%) patients achieved complete remission, and 7 (87.50%) patients achieved complete or partial remission. All 8 patients with HCV infection received antiviral agents and the load of HCV virus were undetectable at the time of rituximab treatment. No adverse effect of rituximab on HCV plasma viremia or hepatic transaminase levels was observed during the follow-up. Conclusions: This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials. PLA2R associated membranous nephropathy phospholipase A2 receptor HCV infection rituximab Figures Figure 1 Introduction Hepatitis C virus (HCV) infection is a global health problem, with an estimated 71 million people chronically infected with HCV. In 2015, the global incidence of HCV was 23.7 cases per 100,000 population, and the estimated number of new diagnoses of HCV infection in 2015 was 17.5 million 1 . Despite the availability of effective anti-HCV drugs, reactivation of HCV is a significant problem for chronic HCV patients who received the treatment of immunosuppressive therapy 2,3 . It has been demonstrated that although rituximab greatly improved the prognosis of patients with hematological malignancies and rheumatoid arthritis, it is also associated with HCV reactivation 4,5 . Recently, rituximab has emerged as an effective treatment option for patients with phospholipase A2 receptor (PLA2R) associated membranous nephropathy (MN) 6 . However, despite the increasing use of rituximab, there is a lack of studies related to HCV reactivation in patients with PLA2R associated MN and HCV infection receiving rituximab. With the increased use of rituximab in patients with PLA2R associated MN, there is an urgent need to determine the risk of HCV reactivation in these populations. Therefore, we included a group of patients with PLA2R associated MN in combination with HCV infection treated with rituximab to determine the efficacy and safety of rituximab treatment in these patients, especially the risk of HCV reactivation. Methods Study Design and Patients This is a retrospective study. A total of 598 adult patients with PLA2R associated MN who received rituximab at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2021 were screened. We identified 8 cases of PLA2R associated MN with a previous or active viral infection with HCV. A diagnosis of HCV infection was serum positivity for HCV antibody (HCVAb) or detectable HCV RNA. The exclusion criteria were as follows: (1) patients together with additional glomerular diseases including secondary membranous nephropathy; (2) patients who had poor follow-up compliance while receiving rituximab; (3) patients with a follow up period less than 12 months; (4) patients who were co-infection with hepatitis B virus; (5) patients who received other immunosuppressive agents except for rituximab simultaneously; (6) patients who are with cryoglobulinemia or hypocomplementemia. Informed consent was derived from the participants. Treatment regimens for all patients were based on the recommendations in relevant guidelines 6 . We also reviewed the guidelines about the study participants to confirm that our study was conducted in accordance with the relevant guidelines/regulations. The ethics committee of the First Affiliated Hospital of Zhengzhou University authorized the study. Immunosuppressive regimen and follow-up The patients in this study all received a regimen of rituximab (375 mg/m 2 x 4 doses or 1 g x 2 doses). The decision of whether or not to receive one more cycle of rituximab was made at the 6th month based on the degree of anti-PLA2R antibody or CD 19+ cells count. General clinical information, including gender, age, blood pressure, body mass index, pathological information, and past treatment plans were gathered from medical records. Routine blood examinations, liver and kidney function tests, blood lipids, 24-h urine protein, anti-PLA2R antibody, circulating B-cell quantity, and HCV viral titers were collected at the time of rituximab infusion and repeated at 1-3 months interval after rituximab administration. According to age, gender, race, and serum creatinine levels, the estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration algorithm. Definitions and Monitoring of HCV reactivation HCV reactivation was defined as the reappearance of HCV RNA after rituximab treatment. All patients were screened for HCV (HCVAb and HCV RNA) prior to rituximab treatment and monthly after receiving rituximab, along with routine liver function tests. Serum HCVAb was determined by electrochemiluminescence using the Cobase immunoassay analyzer and the immunoassay "ECLA" (Roche Diagnostic, Germany). Plasma HCV-RNA virus load were determined using real-time polymerase chain reaction on the ABI7500 Fluorescent Quantitative PCR Instrument (Applied Biosystems, USA). The lower limit of HCV RNA detection was 500 IU/mL in our study. Treatment response According to the 2021 Kidney Disease Improving Global Outcomes recommendations, complete remission was defined as urinary protein excretion <0.3 g/24 hours with normal serum albumin and serum creatinine. Partial remission was defined as proteinuria <3.5 g/24 hours or a reduction of ≥50% from peak, improvement or normalization of serum albumin, and stable serum creatinine. Immunologic remission was defined as the titer of anti-PLA2R antibody below 2 RU/ml. Statistical Analysis Data was expressed as mean ± standard deviation, median, interquartile range, or percentages. Paired sample t-test or the Wilcoxon matched pair signed-rank (two samples) test was used for comparison between the two groups according to the distribution of data. The SPSS 24.0 software program was used for statistical analysis, and two-sided p-values were calculated. Results 3.1 Baseline characteristics at rituximab infusion There were 8 patients with PLA2R associated MN and HCV infection who received rituximab treatment. The clinical characteristics of the patients at baseline was presented in Table 1. There were 5 male patients and 3 female patients, with a mean age of 50.13±4.29 years old. Anti-PLA2R antibody was positive in all 8 patients. The baseline level of proteinuria was 5.29 (3.53, 6.51) g/24h, serum albumin was 28.00 (25.05, 32.55) g/L, and eGFR was 71.10 (48.54, 89.97) ml/min/1.73m 2 . According to the chronic kidney disease staging guidelines of Kidney Disease: Improving Global Outcomes, 2, 3, and 3 patients had stage 1, 2, and 3 chronic kidney disease, respectively. Following diagnosis by percutaneous renal biopsy, all patients were administered other immunosuppressant therapy before rituximab treatment, including cyclophosphamide combined with steroids in 2 patients, cyclosporine combined with steroids in 1 patient, and tacrolimus in 8 patients. In previous immunosuppressive treatment regimens, 5 patients achieved complete remission. However, during drug discontinuation or reduction, nephrotic syndrome relapsed. The other 3 patients did not achieve partial or complete remission of nephrotic syndrome in previous immunosuppressive treatment regimens. 3.2 Histological findings All patients underwent kidney biopsy and were diagnosed with PLA2R associated MN. The renal biopsy findings are detailed in Table 2. LM showed a median of 33 glomeruli per biopsy (range 15-73). Interstitial fibrosis and tubular atrophy were present in 3 cases. Immunostaining revealed granular glomerular capillary wall positive for IgG and C3 in all patients. PLA2R and IgG4 staining was tested by renal biopsy staining and positive in all 8 cases. EM was performed in all patients and showed features of MN with subepithelial electron dense deposits. There were mostly Stage I-II and II-III and the remaining cases showed deposits of stage II. Tubuloreticular inclusions were not found in all patients. Mesangial, intramembranous, and subendothelial deposits were not seen in all 8 patients. 3.3 Basic information of HCV infection As shown in Table 3, in 5 patients, the diagnosis of HCV infection predated the renal biopsy, and in 3 patients the diagnosis of HCV infection and PLA2R associated MN was made at the same time. All 8 patients with HCV infection received antiviral agents and the load of HCV virus were undetectable at the time of rituximab treatment. Patients with HCV infection are prone to comorbid glomerular diseases such as membranoproliferative glomerulopathy, MN, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. In particular, patients with HCV infection who have comorbid membranoproliferative glomerulopathy will have cryoglobulinemia and hypocomplementemia, which was not existed in all 8 patients in this study (Table 1). 3 .4 Clinical and immunological outcomes During the follow-up period of 19.00 (16.00, 25.25) months, the prevalence of patients with clinical remission increased from 0.00% at baseline to 50.00% (4/8), 75.00% (6/8), and 87.50 (7/8) at month 6, month 12, and last visit. Median CD19+ B cell count was 292.00/mm 3 (IQR, 188.00 to 327.75) at baseline. Circulating CD19+ B cells at month 6 were significantly reduced compared with the baseline level ( P =0.017). At month 12 and last visit, the number of CD19+ B cells had recovered to some extent. However, there were still significant differences in CD19+ B cells between the baseline level and the level at month 12 and last visit after rituximab intervention ( P =0.028, P =0.018) (Table 4, Figure 1). At month 6, month 12, and last visit, anti-PLA2R antibody titers [6.60 (2.00, 18.00) vs 34.20 (18.20, 85.30) RU/ml, P =0.059; 2.00 (2.00, 2.50) vs 34.20 (18.20, 85.30) RU/ml, P =0.028; 2.00 (2.00, 2.00) vs 34.20 (18.20, 85.30 RU/ml, P =0.018] were lower compared with the baseline levels (Table 4, Figure 1). From baseline to month 6, month 12, and last visit, there was a decrease in prevalence of anti-PLA2R positive patients from 100.00% (8/8) to 50.00% (4/8), 12.50% (1/8), and 0.00% (0/0). In term of proteinuria, the results showed that median levels of proteinuria were decrease from 5.29 (3.53, 6.51) g/d at baseline to 1.10 (0.38, 1.85) g/d at month 12 and 0.62 (0.19, 0.91) g/d at last visit, respectively ( P =0.041, P =0.028). At month 6, serum albumin increased significantly [27.30 (20.20, 34.40) vs 23.70 (18.70, 25.70) g/L, P =0.017] compared with the baseline levels. Continued improvements of serum albumin were observed between baseline and last visit (Table 4, Figure 1). Renal function was preserved since rituximab infusion in all patients demonstrated by serum creatinine and eGFR. This phenomenon also showed that the reduction of proteinuria caused by rituximab might maintain the stability of renal function to some extent (Table 4, Figure 1). 3.5 Safety analysis of rituximab in patients with PLA2R associated MN and HCV infection This study showed the safety of rituximab in patients with PLA2R associated MN and HCV infection, which was demonstrated by no increase in HCV virus load and stable liver function tests after rituximab therapy (Figure 1). During the follow-up, we also did not observe other adverse events including the occurrence of allergic reaction and infection. Discussion In this study, we retrospectively analyzed demographic characteristics, clinical remission rete, liver function and HCV load changes in patients with PLA2R associated MN and HCV infection treated with rituximab. Immunosuppression is known to increase HCV virus load and accelerate the progression of chronic HCV liver disease 7-9 , and previous studies suggested a similar risk with rituximab treatment 10 . This limited the application of rituximab in patients with PLA2R associated MN and HCV infection. However, unlike HBV and HIV, HCV infection can be completely and permanently cured through antiviral therapy, as HCV does not have a long-term storage in the body. Furthermore, the widespread and effective application of antiviral drugs in clinical practice brings new hope to the application of rituximab in patients with PLA2R associated MN and HCV infection in recent years. At present, there are no studies about the safety of rituximab in patients with PLA2R associated MN and HCV infection. However, in other diseases such as lymphoma and other HCV-associated nephritis, the results of the studies are inconsistent as to whether rituximab affects the replication of HCV. To date, in very small cohorts of patients with haematological malignancies receiving R-CHOP regimens, results had showed the elevated serum HCV virus load during or after rituximab-based chemotherapy 11-13 . In a larger cohort study of patients with HCV-associated diffuse large B-cell lymphoma 14 , serum HCV virus load increased significantly during rituximab-based chemotherapy and decreased significantly thereafter. There were also some studies similar to ours that confirm the safety of rituximab. A prospective controlled trial showed that among 31 patients with severe HCV associated cryoglobulinemia vasculitis who were randomly treated with rituximab and antiviral therapy, the complete remission rate of kidney disease was high and the safety was good 15 . Consistent with the above studies, other reports have shown the safety of rituximab in HCV infected individuals. These reports showed that there was no increase in HCV viremia after rituximab treatment, and liver function tests were stable 16 . In our trial, we found no evidence of worsening of HCV infection. There were no significant changes in plasma viral levels over time and no biochemical evidence of worsening hepatitis. Rituximab treatment was well tolerated, and no serious infections were detected. We considered that it may be related to the following reasons. Firstly, in the previous studies mentioned above, most of patients still had a high HCV virus load at rituximab infusion, and these patients also received cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment when receiving rituximab treatment, which may be the reason for the increase of HCV virus load. In our study, patients received antiviral therapy before receiving rituximab treatment, and HCV virus was not detected at rituximab infusion. Moreover, in our study, patients did not receive other immunosuppressants except for rituximab, which may be one of the reasons why our results differ from some previous studies. Our current study has several limitations. First, because the study was a retrospective study and the number of cases included in the study was low, our results should be interpreted with caution and should be further evaluated in a large study of prospective design. Second, due to the small sample size, we did not compare the difference in HCV viral load between patients treated with rituximab and those not treated with rituximab. Whether rituximab is an independent factor contributing to the increase of HCV viral load in patients with PLA2R associated MN is unknown and should be investigated in further studies. In conclusion, our findings suggest that rituximab does not lead to a significant increase in HCV virus load in patients with PLA2R associated MN and HCV infection. On the basis of successful eradication of HCV virus with antiviral drugs, rituximab may be an effective regimen for treating patients with PLA2R associated MN with HCV infection. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials. Declarations Acknowledgement Thanks to the support of Renal Pathology Laboratory, the First Affiliated Hospital of Zhengzhou University. Contributions L.T. and X.D.L. designed the study. X.D.L. and Y.X.H. made the tables and figures, and wrote the manuscript. Y.X.H., H.Y.Z and Y.L.W collected the data. Y.H.G. and M.J.R. performed the statistical analysis. L.T. revised the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript. Data Availability Data could be obtained upon request to the corresponding author. Supplementary Information The authors declare that there is no conflict of interests. References Spearman, C., Dusheiko, G., Hellard, M. & Sonderup, M. Hepatitis C. Lancet (London, England) 394 , 1451-1466 (2019). Lee, H. et al. Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy. Gut and liver 11 , 870-877 (2017). Chen, M. et al. Incidence and antiviral response of hepatitis C virus reactivation in lupus patients undergoing immunosuppressive therapy. Lupus 24 , 1029-1036 (2015). Lin, K., Lin, J., Tseng, W. & Cheng, T. Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 46 , 65-67 (2013). Nooka, A., Shenoy, P., Sinha, R., Lonial, S. & Flowers, C. Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma treated with rituximab: a case report and review of literature. Clinical lymphoma, myeloma & leukemia 11 , 379-384 (2011). KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney international 100 , S1-S276 (2021). Soto, B. et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. Journal of hepatology 26 , 1-5 (1997). Heneghan, M. Long-term outcome of hepatitis C infection after liver transplantation. The New England journal of medicine 335 , 522; author reply 522-523 (1996). Magy, N. et al. Effects of corticosteroids on HCV infection. International journal of immunopharmacology 21 , 253-261 (1999). Sansonno, D. et al. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood 101 , 3818-3826 (2003). Pitini, V. et al. HCV genotype 2 as a risk factor for reactivation in patients with B-cell lymphoma undergoing rituximab combination chemotherapy. British journal of haematology 150 , 116-118 (2010). Coppola, N. et al. Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 44 , 49-54 (2012). Marignani, M. et al. HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin's lymphoma treated with rituximab-containing regimens. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 43 , 139-142 (2011). Ennishi, D. et al. Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis. Blood 116 , 5119-5125 (2010). Saadoun, D. et al. Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia. Blood 116 , 326-334; quiz 504-325 (2010). Sneller, M., Hu, Z. & Langford, C. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis and rheumatism 64 , 835-842 (2012). Tables Table 1 Baseline characteristics of MN patients with HCV infection at RTX infusion. Variables All patients (n=8) DEMOGRAPHICS Gender (male/female) 5/3 Age (year) 50.13±4.29 BMI (kg/m 2 ) 24.2±4.02 BP (mmHg) Systolic 132.25±11.03 Diastolic 80.63±11.55 Period of follow-up (months) 19.00 (16.00, 25.25) Median time from the use of RTX to MN diagnosis (months) 16.00 (9.75, 39.50) Median time from the use of RTX to HCV diagnosis (months) 58.50 (15.25, 90.75) Median time from HCV diagnosis to MN diagnosis (months) 28.50 (0.00, 67.00) Hemoglobin (g/L) 117.30±19.84 Creatinine (µmol/L) 93.00 (79.00, 150.50) eGFR (ml/min/1.73m 2 ) 71.10 (48.54, 89.97) eGFR >90 2 eGFR 60-89 3 eGFR 30-59 3 eGFR 15-29 0 eGFR<15 0 Proteinuria (g/24h) 5.29 (3.53, 6.51) Albumin (g/L) 28.00 (25.05, 32.55) Anti- PLA2R antibody titer (RU/mL) 34.20 (18.20, 85.30) CD19 (/mm 3 ) 292.00 (188.00, 327.75) CD4 (/mm 3 ) 558.50 (489.00, 1011.25) Number (%) of patients with negative cryoglobulin test (N, %) 8 (100.00%) Number (%) of patients with negative rheumatoid factor (N, %) 8 (100.00%) C3 (g/L) 0.91 (0.84, 0.99) C4 (g/L) 0.26 (0.23, 0.31) Number (%) of patients with, (N, %) Hepatitis C occured before MN diagnosis 6 (75.00%) Simultaneous diagnosis of MN and hepatitis C 2 (25.00%) Number (%) of patients with, (N, %) Relapse 5 (62.50%) Ineffective 3 (37.50%) Previous therapies Prednisone + cyclophosphamide, n 2 Prednisone + cyclosporine, n 1 Tacrolimus, n 8 Mycophenolate mofetil, n 0 Data presented as median (first-third interquartile range) or mean ± SD or number (percentage). RTX, rituximab; MN, membranous nephropathy; HCV, hepatitis C virus; BP, blood pressure; eGFR, estimated glomerular filtration rate; anti- PLA2R antibody, anti-phospholipase A2 receptor antibody. Table 2 Pathological characteristics of patients. no PLA2R staining Total glomeruli Globally sclerotic glomeruli IFTA (%) IF IgG4 EM stage Subepithelial Deposits Intramembranous Deposits Subendothelial Deposits Mesangial Deposits TRIs HCV load at renal biopsy 1 Pos 24 0 0 IgG++, IgA±, IgM-, C3+，C4-，C1q-，FRA- 2+ I-II Yes No No No No undetectable 2 Pos 34 1 0 IgG++, IgA±, IgM+, C3++，C4-，C1q-，FRA- 2+ II-III Yes No No No No undetectable 3 Pos 15 0 0 IgG++, IgA-, IgM+, C3+，C4±，C1q-，FRA- 1+ II Yes No No No No undetectable 4 Pos 43 0 10 IgG+++, IgA-, IgM+, C3+，C4-，C1q-，FRA－ 2+ II-III Yes No No No No 1.29×10 6 IU/ml 5 Pos 73 0 25 IgG++, IgA-, IgM±, C3+，C4-，C1q-，FRA－ 2+ II Yes No No No No undetectable 6 Pos 33 3 10 IgG+++, IgA-, IgM+, C3+，C4-，C1q-，FRA－ 2+ I-II Yes No No No No undetectable 7 Pos 33 0 0 IgG++, IgA±, IgM±, C3+，C4-，C1q-，FRA－ 2+ II-III Yes No No No No undetectable 8 Pos 18 0 0 IgG++, IgA-, IgM-, C3+，C4-，C1q-，FRA－ 1+ I-II Yes No No No No undetectable PLA2R, phospholipase A2 receptor; IFTA, interstitial fibrosis tubular atrophy; FRA, fibrin related antigen; EM, electron microscope; IF, immunofluorescence; HCV, hepatitis C virus; Neg, negative; Pos, positive. Table 3 Clinical findings in MN patients with hepatitis C. Cases Sex Age Treatment of hepatitis C Hepatitis C virus load at RTX infusion Time from identification of hepatitis C to renal biopsy Time from identification of hepatitis C to RTX infusion Hepatitis C occurred before/simultaneous MN diagnosis 1 male 42 Sofosbuvir undetectable 14 91 before 2 female 53 Sofosbuvir undetectable 74 90 before 3 female 50 Sofosbuvir undetectable 43 51 before 4 male 45 Ledipasvir and Sofosbuvir Tablets undetectable 0 15 simultaneous 5 male 53 Peginterferon alfa-2a undetectable 195 241 before 6 male 53 Elbasvir and Grazoprevir Tablets undetectable 0 16 simultaneous 7 female 53 Ledipasvir and Sofosbuvir Tablets undetectable 46 66 before 8 male 52 Ledipasvir and Sofosbuvir Tablets undetectable 0 6 simultaneous Table 4 Efficacy outcome variables Variables Baseline Month 6 Month 12 Last visit Remission, complete and partial (N, %) NA 4 (50.00%) 6 (75.00%) 7 (87.50%) Remission, complete (N, %) NA 2 (25.00%) 3 (37.50%) 5 (62.50%) Proteinuria (g/24h) 5.29 (3.53, 6.51) 1.37 (0.46, 7.63) 1.10 (0.38, 1.85) a 0.62 (0.19, 0.91) a,b,c Albumin (g/L) 28.00 (25.05, 32.55) 35.20 (30.70, 40.00) a 42.30 (32.00, 44.30) a,b 42.30 (38.90, 43.50) a,b Serum creatinine (µmol/L) 93.00 (79.00, 150.50) 100.00 (89.25, 159.50) 95.00 (85.50, 150.50) 90.50 (83.00, 191.00) eGFR (ml/min/1.73 m 2 ) 71.10 (48.54, 89.97) 55.83 (45.56, 86.69) 65.27 (46.81, 73.71) 67.24 (33.23, 79.90) anti-PLA2R-Ab–positive patients (N, %) 8 (100.00%) 4 (50.00%) 1 (12.50%) 0 (0.00%) anti-PLA2R-Ab–depleted patients (N, %) NA 3 (37.50%) 6 (75.00%) 8 (100.00%) anti- PLA2R-Ab titer (RU/mL) 34.20 (18.20, 85.30) 6.60 (2.00, 18.00) a 2.00 (2.00, 2.50) a 2.00 (2.00, 2.00) a CD19 (/mm 3 ) 292.00 (188.00, 327.75) 13.00 (0.00, 87.50) a 22.00 (8.50, 190.50) a 235.00 (45.00, 298.00) a Patients with undetectable hepatitis C virus (N, %) 8 (100.00%) 8 (100.00%) 8 (100.00%) 8 (100.00%) Data presented as number (percentage) or median (first-third interquartile range). a Stands for p < 0.05 vs baseline; b Stands for p < 0.05 vs month 6; c Stands for p < 0.05 vs month 12. eGFR, estimated glomerular filtration rate; anti-PLA2R-Ab, anti-phospholipase A2 receptor antibody; CD, Cluster of differentiation. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Sep, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 11 Jun, 2024 Reviews received at journal 04 Jun, 2024 Reviewers agreed at journal 21 May, 2024 Reviews received at journal 16 Apr, 2024 Reviewers agreed at journal 04 Apr, 2024 Reviewers agreed at journal 23 Mar, 2024 Reviewers agreed at journal 23 Mar, 2024 Reviewers agreed at journal 18 Mar, 2024 Reviewers invited by journal 18 Mar, 2024 Editor assigned by journal 18 Mar, 2024 Editor invited by journal 12 Mar, 2024 Submission checks completed at journal 12 Mar, 2024 First submitted to journal 20 Feb, 2024 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-3974488","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":278560735,"identity":"cda422a3-b4b2-46a6-b46b-ecbc44680e5d","order_by":0,"name":"Xiaodan Li","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiaodan","middleName":"","lastName":"Li","suffix":""},{"id":278560736,"identity":"7a3a60a3-ca82-4efa-97f6-0da5c6cd79d9","order_by":1,"name":"Yingxuan Hao","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yingxuan","middleName":"","lastName":"Hao","suffix":""},{"id":278560737,"identity":"f1333fa5-896d-4540-a8ef-94c8b6ebea40","order_by":2,"name":"Mingjing Ren","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Mingjing","middleName":"","lastName":"Ren","suffix":""},{"id":278560738,"identity":"600e8c1a-679f-4db8-bce3-75d90ee47398","order_by":3,"name":"Yanhong Guo","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yanhong","middleName":"","lastName":"Guo","suffix":""},{"id":278560739,"identity":"cecfce4d-f120-45b4-8119-a91c4e747643","order_by":4,"name":"Huayan Zhao","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Huayan","middleName":"","lastName":"Zhao","suffix":""},{"id":278560740,"identity":"4be43af5-e288-46ec-90e0-e652c6546b14","order_by":5,"name":"Yulin Wang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yulin","middleName":"","lastName":"Wang","suffix":""},{"id":278560741,"identity":"4a140496-580b-4aec-813c-257de26d5107","order_by":6,"name":"Lin Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYLCCBwYMchAWGxGqeUBEggGDMalaGBgSG4jWYs9+9vCLhII76fP7zxgwfCg7zMA/u4GALTx5aRYJBs9yGxvOGDDOOHeYQeLOAUIOyzEzSDA4nNvM2GPAzNt2mMFAIoGAFv43YC3pbMw8Bsx/idIikWP8AKglgYcNqIWRKC033pgBA/mw4QwetoKDPefSeSRuENDC3p9j/OHDn8Py8v2HNz74UWYtxz+DgBYgYJOAsQ4wQCOKEGD+QIyqUTAKRsEoGMEAAL9dPYSDHPRnAAAAAElFTkSuQmCC","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Lin","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2024-02-21 04:15:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3974488/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3974488/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-72082-y","type":"published","date":"2024-09-09T15:57:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52709926,"identity":"16071bf3-bb3a-4b97-8fc5-a89004dc175f","added_by":"auto","created_at":"2024-03-14 19:49:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":908348,"visible":true,"origin":"","legend":"\u003cp\u003eSerial levels of proteinuria (A), serum albumin (B), serum creatinine (C), eGFR (D), CD19 positive B cells (E), anti-PLA2R antibody (F), ALT (G), AST (H), and TBIL (I) after the rituximab treatment in all patients who had been followed up for a minimum of 12 months. The bars show median with interquartile range for each variable. ns \u003cem\u003eP\u003c/em\u003e\u0026gt;0.05 vs baseline; *\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs baseline; **\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01 vs baseline; ***\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001 vs baseline.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3974488/v1/a33a21b81a49401180575b64.png"},{"id":64619037,"identity":"d12396c0-71ae-484b-ba4d-329bd4f95b0f","added_by":"auto","created_at":"2024-09-16 16:10:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1550831,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3974488/v1/f5766351-58a6-40e1-b4d7-8f448805bb1a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and HCV infection","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatitis C virus (HCV) infection is a global health problem, with an estimated 71 million people chronically infected with HCV. In 2015, the global incidence of HCV was 23.7 cases per 100,000 population, and the estimated number of new diagnoses of HCV infection in 2015 was 17.5 million\u0026nbsp;\u003csup\u003e1\u003c/sup\u003e. Despite the availability of effective anti-HCV drugs, reactivation of HCV is a significant problem for chronic HCV patients who received the treatment of immunosuppressive therapy\u0026nbsp;\u003csup\u003e2,3\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIt has been demonstrated that although rituximab greatly improved\u0026nbsp;the prognosis of patients with hematological malignancies and rheumatoid arthritis, it is also associated with HCV reactivation\u0026nbsp;\u003csup\u003e4,5\u003c/sup\u003e. Recently, rituximab has emerged as an effective treatment option for patients with\u0026nbsp;phospholipase A2 receptor\u0026nbsp;(PLA2R) associated membranous nephropathy (MN)\u0026nbsp;\u003csup\u003e6\u003c/sup\u003e. However, despite the increasing use of rituximab, there is a lack of studies related to HCV reactivation in patients with PLA2R associated MN and HCV infection receiving rituximab. With the increased use of rituximab in patients with PLA2R associated MN, there is an urgent need to determine the risk of HCV reactivation in these populations. Therefore, we included a group of patients with PLA2R associated MN in combination with HCV infection treated with rituximab to determine the efficacy and safety of rituximab treatment in these patients, especially the risk of HCV reactivation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective study. A total of 598 adult patients with PLA2R associated MN who received rituximab at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2021 were screened. We identified 8 cases of PLA2R associated MN with a previous or active viral infection with HCV.\u0026nbsp;A diagnosis of HCV infection was serum positivity for HCV antibody (HCVAb) or detectable HCV RNA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows: (1) patients together with additional glomerular diseases including secondary membranous nephropathy; (2) patients who had poor follow-up compliance while receiving rituximab; (3) patients with a follow up period less than 12 months; (4) patients who were co-infection with hepatitis B virus; (5) patients who received other immunosuppressive agents except for rituximab simultaneously; (6) patients who are with cryoglobulinemia or hypocomplementemia.\u0026nbsp;Informed consent was derived from the participants.\u0026nbsp;Treatment regimens for all patients were based on the recommendations in relevant guidelines\u003csup\u003e6\u003c/sup\u003e. We also reviewed the guidelines about the study participants to confirm that our study was conducted in accordance with the relevant guidelines/regulations. \u0026nbsp;The ethics committee of the First Affiliated Hospital of Zhengzhou University authorized the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunosuppressive regimen and follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients in this study all received a regimen of rituximab (375 mg/m\u003csup\u003e2\u003c/sup\u003e x 4 doses or 1 g x 2 doses). The decision of whether or not to receive one more cycle of rituximab was made at the 6th month based on the degree of anti-PLA2R\u0026nbsp;antibody\u0026nbsp;or\u0026nbsp;CD 19+\u0026nbsp;cells count.\u003c/p\u003e\n\u003cp\u003eGeneral clinical information, including gender, age, blood pressure, body mass index, pathological information, and past treatment plans were gathered from medical records. Routine blood examinations, liver and kidney function tests, blood lipids, 24-h urine protein, anti-PLA2R antibody,\u0026nbsp;circulating B-cell quantity, and HCV viral titers\u0026nbsp;were collected at the time of rituximab infusion and repeated at 1-3 months interval after rituximab administration.\u0026nbsp;According to age, gender, race, and serum creatinine levels, the estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration algorithm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMonitoring of HCV reactivation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHCV reactivation was defined as the reappearance of HCV RNA after\u0026nbsp;rituximab treatment.\u0026nbsp;All patients were screened for HCV (HCVAb and HCV RNA) prior to rituximab treatment and monthly after receiving rituximab, along with routine\u0026nbsp;liver function\u0026nbsp;tests. Serum HCVAb was determined by electrochemiluminescence using the Cobase immunoassay analyzer and the immunoassay \u0026quot;ECLA\u0026quot; (Roche Diagnostic, Germany). Plasma HCV-RNA virus load were determined using real-time polymerase chain reaction on the ABI7500 Fluorescent Quantitative PCR Instrument (Applied Biosystems, USA). The lower limit of HCV RNA detection was 500 IU/mL in our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment response\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the 2021 Kidney Disease Improving Global Outcomes recommendations,\u0026nbsp;complete remission was defined as urinary protein excretion \u0026lt;0.3 g/24 hours with normal serum albumin and serum creatinine. Partial remission was defined as proteinuria \u0026lt;3.5 g/24 hours or a reduction of \u0026ge;50% from peak, improvement or normalization of serum albumin, and stable serum creatinine.\u0026nbsp;Immunologic remission was defined as the titer of anti-PLA2R antibody below 2 RU/ml.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData was expressed as mean \u0026plusmn; standard deviation, median, interquartile range, or percentages. Paired sample t-test or the Wilcoxon matched pair signed-rank (two samples) test was used for comparison between the two groups according to the distribution of data. The SPSS 24.0 software program was used for statistical analysis, and two-sided p-values were calculated.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Baseline characteristics at rituximab infusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were 8 patients with PLA2R associated MN and HCV infection who received rituximab treatment. The clinical characteristics of the patients at baseline was presented in Table 1. There were 5 male patients and 3 female patients, with a mean age of 50.13\u0026plusmn;4.29 years old. Anti-PLA2R antibody was positive in all 8 patients. The baseline level of proteinuria was\u0026nbsp;5.29 (3.53, 6.51) g/24h, serum albumin was\u0026nbsp;28.00 (25.05, 32.55) g/L, and eGFR was\u0026nbsp;71.10 (48.54, 89.97)\u0026nbsp;ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. According to the chronic kidney disease staging guidelines of Kidney Disease: Improving Global Outcomes, 2, 3, and 3 patients had stage 1, 2, and 3 chronic kidney disease, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing diagnosis by percutaneous renal biopsy, all patients were administered other immunosuppressant therapy before rituximab treatment, including\u0026nbsp;cyclophosphamide combined with steroids in 2 patients, cyclosporine combined with steroids in 1 patient, and tacrolimus in 8 patients. In previous immunosuppressive treatment regimens, 5 patients achieved complete remission. However, during drug discontinuation or reduction, nephrotic syndrome relapsed. The other 3 patients did not achieve partial or complete remission of nephrotic syndrome in previous immunosuppressive treatment regimens.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eHistological findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients underwent kidney biopsy and were diagnosed with PLA2R associated MN. The renal biopsy findings are detailed in Table 2. LM showed a median of 33 glomeruli per biopsy (range 15-73). Interstitial fibrosis and tubular atrophy were present in 3 cases. Immunostaining revealed granular glomerular capillary wall positive for IgG and C3 in all patients.\u0026nbsp;PLA2R and IgG4 staining was tested by renal biopsy staining and positive in all 8 cases. EM was performed in all patients and showed features of MN with subepithelial electron dense deposits. There were mostly Stage I-II and II-III and the remaining cases showed deposits of stage II. Tubuloreticular inclusions were not found in all patients. Mesangial,\u0026nbsp;intramembranous,\u0026nbsp;and\u0026nbsp;subendothelial deposits were not seen in all 8 patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Basic information of HCV infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 3, in 5 patients, the diagnosis of HCV infection predated the renal biopsy, and in 3 patients the diagnosis of HCV infection and PLA2R associated MN was made at the same time. All 8 patients with HCV infection received antiviral agents and the load of HCV virus were undetectable at the time of rituximab treatment. Patients with HCV infection are prone to comorbid glomerular diseases such as membranoproliferative glomerulopathy, MN, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. In particular, patients with HCV infection who have comorbid membranoproliferative glomerulopathy will have cryoglobulinemia and hypocomplementemia, which was not existed in all 8 patients in this study (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e.4\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eClinical and immunological outcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the follow-up period of\u0026nbsp;19.00 (16.00, 25.25)\u0026nbsp;months, the prevalence of patients with clinical remission increased from 0.00% at baseline to 50.00% (4/8), 75.00% (6/8), and 87.50 (7/8) at month 6, month 12, and last visit. Median CD19+ B cell count was\u0026nbsp;292.00/mm\u003csup\u003e3\u003c/sup\u003e (IQR,\u0026nbsp;188.00 to 327.75) at baseline. Circulating CD19+ B cells at month 6 were significantly reduced compared with the baseline level (\u003cem\u003eP\u003c/em\u003e=0.017). At month 12 and last visit, the number of CD19+ B cells had recovered to some extent. However, there were still significant differences in CD19+ B cells between the baseline level and the level at month 12 and last visit after rituximab intervention (\u003cem\u003eP\u003c/em\u003e=0.028,\u0026nbsp;\u003cem\u003eP\u003c/em\u003e=0.018) (Table 4, Figure 1).\u003c/p\u003e\n\u003cp\u003eAt month 6, month 12, and last visit, anti-PLA2R antibody titers [6.60 (2.00, 18.00)\u0026nbsp;vs\u0026nbsp;34.20 (18.20, 85.30)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eRU/ml, \u003cem\u003eP\u003c/em\u003e=0.059;\u0026nbsp;2.00 (2.00, 2.50)\u0026nbsp;vs\u0026nbsp;34.20 (18.20, 85.30)\u0026nbsp;RU/ml, \u003cem\u003eP\u003c/em\u003e=0.028;\u0026nbsp;2.00 (2.00, 2.00)\u0026nbsp;vs\u0026nbsp;34.20 (18.20, 85.30\u0026nbsp;RU/ml, \u003cem\u003eP\u003c/em\u003e=0.018] were lower compared with the baseline levels (Table 4, Figure 1). From baseline to month 6, month 12, and last visit, there was a decrease in prevalence of anti-PLA2R positive patients from 100.00% (8/8) to 50.00% (4/8), 12.50% (1/8), and 0.00% (0/0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn term of proteinuria, the results showed that\u0026nbsp;median levels of proteinuria were decrease from\u0026nbsp;5.29 (3.53, 6.51) g/d at baseline to\u0026nbsp;1.10 (0.38, 1.85) g/d at month 12 and 0.62 (0.19, 0.91) g/d at last visit, respectively (\u003cem\u003eP\u003c/em\u003e=0.041, \u003cem\u003eP\u003c/em\u003e=0.028). At month 6,\u0026nbsp;serum albumin increased significantly [27.30 (20.20, 34.40)\u0026nbsp;vs\u0026nbsp;23.70 (18.70, 25.70)\u0026nbsp;g/L,\u0026nbsp;\u003cem\u003eP\u003c/em\u003e=0.017] compared with the baseline levels. Continued improvements of serum albumin were observed between baseline and last visit (Table 4, Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRenal function was preserved since rituximab infusion in all patients demonstrated by serum creatinine and eGFR. This phenomenon also showed that the reduction of\u0026nbsp;proteinuria caused by rituximab might maintain the stability of renal function to\u0026nbsp;some\u0026nbsp;extent\u0026nbsp;(Table 4, Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Safety analysis of rituximab in patients with PLA2R associated MN and HCV infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study showed the safety of rituximab in patients with PLA2R associated MN and HCV infection, which was demonstrated by no increase in HCV virus load and stable liver function tests after rituximab therapy (Figure 1). During the follow-up, we also did not observe other adverse events including the occurrence of allergic reaction and infection.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we retrospectively analyzed demographic characteristics, clinical remission rete, liver function and HCV load changes in patients with PLA2R associated MN and HCV infection treated with rituximab.\u003c/p\u003e\n\u003cp\u003eImmunosuppression is known to increase HCV virus load and accelerate the progression of chronic HCV liver disease\u0026nbsp;\u003csup\u003e7-9\u003c/sup\u003e, and previous studies suggested a similar risk with rituximab treatment\u0026nbsp;\u003csup\u003e10\u003c/sup\u003e. This limited the application of rituximab in patients with PLA2R associated MN and HCV infection. However, unlike HBV and HIV, HCV infection can be completely and permanently cured through antiviral therapy, as HCV does not have a long-term storage in the body. Furthermore, the widespread and effective application of antiviral drugs in clinical practice brings new hope to the application of rituximab in patients with PLA2R associated MN and HCV infection in recent years.\u003c/p\u003e\n\u003cp\u003eAt present, there are no studies about the safety of rituximab in patients with PLA2R associated MN and HCV infection. However, in other diseases such as lymphoma and other HCV-associated nephritis, the results of the studies are inconsistent as to whether rituximab affects the replication of HCV. To date, in very small cohorts of patients with haematological malignancies receiving R-CHOP regimens, results had showed the elevated serum HCV virus load during or after rituximab-based chemotherapy\u0026nbsp;\u003csup\u003e11-13\u003c/sup\u003e. In a larger cohort study of patients with HCV-associated diffuse large B-cell lymphoma\u0026nbsp;\u003csup\u003e14\u003c/sup\u003e, serum HCV virus load increased significantly during rituximab-based chemotherapy and decreased significantly thereafter. There were also some studies similar to ours that confirm the safety of rituximab. A prospective controlled trial showed that among 31 patients with severe HCV associated cryoglobulinemia vasculitis who were randomly treated with rituximab and antiviral therapy, the complete remission rate of kidney disease was high and the safety was good\u0026nbsp;\u003csup\u003e15\u003c/sup\u003e. Consistent with the above studies, other reports have shown the safety of rituximab in HCV infected individuals. These reports showed that there was no increase in HCV viremia after rituximab treatment, and liver function tests were stable\u0026nbsp;\u003csup\u003e16\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn our trial, we found no evidence of worsening of HCV infection. There were no significant changes in plasma viral levels over time and no biochemical evidence of worsening hepatitis. Rituximab treatment was well tolerated, and no serious infections were detected. We considered that it may be related to the following reasons. Firstly, in the previous studies mentioned above, most of patients still had a high HCV virus load at rituximab infusion, and these patients also received cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment when receiving rituximab treatment, which may be the reason for the increase of HCV virus load. In our study, patients received antiviral therapy before receiving rituximab treatment, and HCV virus was not detected at rituximab infusion. Moreover, in our study, patients did not receive other immunosuppressants except for rituximab, which may be one of the reasons why our results differ from some previous studies.\u003c/p\u003e\n\u003cp\u003eOur current study has several limitations. First, because the study was a retrospective study and the number of cases included in the study was low, our results should be interpreted with caution and should be further evaluated in a large study of prospective design. Second, due to the small sample size, we did not compare the difference in HCV viral load between patients treated with rituximab and those not treated with rituximab. Whether rituximab is an independent factor contributing to the increase of HCV viral load in patients with PLA2R associated MN is unknown and should be investigated in further studies.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our findings suggest that rituximab does not lead to a significant increase in HCV virus load in patients with PLA2R associated MN and HCV infection. On the basis of successful eradication of HCV virus with antiviral drugs, rituximab may be an effective regimen for treating patients with PLA2R associated MN with HCV infection. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks to the support of Renal Pathology Laboratory, the First Affiliated Hospital of Zhengzhou University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL.T. and X.D.L. designed the study. X.D.L. and Y.X.H. made the tables and figures, and wrote the manuscript. Y.X.H., H.Y.Z and Y.L.W collected the data. Y.H.G. and M.J.R. performed the statistical analysis. L.T. revised the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData could be obtained upon request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSpearman, C., Dusheiko, G., Hellard, M. \u0026amp; Sonderup, M. Hepatitis C. \u003cem\u003eLancet (London, England)\u003c/em\u003e \u003cstrong\u003e394\u003c/strong\u003e, 1451-1466 (2019).\u003c/li\u003e\n\u003cli\u003eLee, H.\u003cem\u003e et al.\u003c/em\u003e Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy. \u003cem\u003eGut and liver\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 870-877 (2017).\u003c/li\u003e\n\u003cli\u003eChen, M.\u003cem\u003e et al.\u003c/em\u003e Incidence and antiviral response of hepatitis C virus reactivation in lupus patients undergoing immunosuppressive therapy. \u003cem\u003eLupus\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 1029-1036 (2015).\u003c/li\u003e\n\u003cli\u003eLin, K., Lin, J., Tseng, W. \u0026amp; Cheng, T. Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis. \u003cem\u003eJournal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi\u003c/em\u003e \u003cstrong\u003e46\u003c/strong\u003e, 65-67 (2013).\u003c/li\u003e\n\u003cli\u003eNooka, A., Shenoy, P., Sinha, R., Lonial, S. \u0026amp; Flowers, C. Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma treated with rituximab: a case report and review of literature. \u003cem\u003eClinical lymphoma, myeloma \u0026amp; leukemia\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 379-384 (2011).\u003c/li\u003e\n\u003cli\u003eKDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. \u003cem\u003eKidney international\u003c/em\u003e \u003cstrong\u003e100\u003c/strong\u003e, S1-S276 (2021).\u003c/li\u003e\n\u003cli\u003eSoto, B.\u003cem\u003e et al.\u003c/em\u003e Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. \u003cem\u003eJournal of hepatology\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 1-5 (1997).\u003c/li\u003e\n\u003cli\u003eHeneghan, M. Long-term outcome of hepatitis C infection after liver transplantation. \u003cem\u003eThe New England journal of medicine\u003c/em\u003e \u003cstrong\u003e335\u003c/strong\u003e, 522; author reply 522-523 (1996).\u003c/li\u003e\n\u003cli\u003eMagy, N.\u003cem\u003e et al.\u003c/em\u003e Effects of corticosteroids on HCV infection. \u003cem\u003eInternational journal of immunopharmacology\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 253-261 (1999).\u003c/li\u003e\n\u003cli\u003eSansonno, D.\u003cem\u003e et al.\u003c/em\u003e Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. \u003cem\u003eBlood\u003c/em\u003e \u003cstrong\u003e101\u003c/strong\u003e, 3818-3826 (2003).\u003c/li\u003e\n\u003cli\u003ePitini, V.\u003cem\u003e et al.\u003c/em\u003e HCV genotype 2 as a risk factor for reactivation in patients with B-cell lymphoma undergoing rituximab combination chemotherapy. \u003cem\u003eBritish journal of haematology\u003c/em\u003e \u003cstrong\u003e150\u003c/strong\u003e, 116-118 (2010).\u003c/li\u003e\n\u003cli\u003eCoppola, N.\u003cem\u003e et al.\u003c/em\u003e Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy. \u003cem\u003eDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 49-54 (2012).\u003c/li\u003e\n\u003cli\u003eMarignani, M.\u003cem\u003e et al.\u003c/em\u003e HCV-positive status and hepatitis flares in patients with B-cell non-Hodgkin\u0026apos;s lymphoma treated with rituximab-containing regimens. \u003cem\u003eDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver\u003c/em\u003e \u003cstrong\u003e43\u003c/strong\u003e, 139-142 (2011).\u003c/li\u003e\n\u003cli\u003eEnnishi, D.\u003cem\u003e et al.\u003c/em\u003e Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis. \u003cem\u003eBlood\u003c/em\u003e \u003cstrong\u003e116\u003c/strong\u003e, 5119-5125 (2010).\u003c/li\u003e\n\u003cli\u003eSaadoun, D.\u003cem\u003e et al.\u003c/em\u003e Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia. \u003cem\u003eBlood\u003c/em\u003e \u003cstrong\u003e116\u003c/strong\u003e, 326-334; quiz 504-325 (2010).\u003c/li\u003e\n\u003cli\u003eSneller, M., Hu, Z. \u0026amp; Langford, C. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. \u003cem\u003eArthritis and rheumatism\u003c/em\u003e \u003cstrong\u003e64\u003c/strong\u003e, 835-842 (2012).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"546\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eTable 1 Baseline characteristics of MN patients with HCV infection at RTX infusion.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll patients (n=8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDEMOGRAPHICS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\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 width=\"65.01831501831502%\"\u003e\n \u003cp\u003eGender (male/female)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e5/3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eAge (year)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e50.13\u0026plusmn;4.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e24.2\u0026plusmn;4.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eSystolic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e132.25\u0026plusmn;11.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eDiastolic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e80.63\u0026plusmn;11.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003ePeriod of follow-up (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e19.00 (16.00, 25.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eMedian time from the use of RTX to MN diagnosis (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e16.00 (9.75, 39.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eMedian time from the use of RTX to HCV diagnosis (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e58.50 (15.25, 90.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eMedian time from HCV diagnosis to MN diagnosis (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e28.50 (0.00, 67.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e117.30\u0026plusmn;19.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eCreatinine (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e93.00 (79.00,\u0026nbsp;150.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e71.10 (48.54, 89.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR \u0026gt;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR 60-89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR 30-59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR 15-29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eeGFR\u0026lt;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eProteinuria (g/24h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e5.29 (3.53, 6.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eAlbumin (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e28.00 (25.05, 32.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eAnti- PLA2R antibody titer (RU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e34.20 (18.20, 85.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eCD19 (/mm\u003csup\u003e3\u003c/sup\u003e) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e292.00 (188.00, 327.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eCD4 (/mm\u003csup\u003e3\u003c/sup\u003e) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e558.50 (489.00, 1011.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eNumber (%) of patients with negative cryoglobulin test (N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eNumber (%) of patients with negative\u0026nbsp;rheumatoid factor\u0026nbsp;(N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eC3 (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e0.91 (0.84, 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eC4 (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e0.26 (0.23, 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (%) of patients with, (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eHepatitis C occured before MN diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e6 (75.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eSimultaneous diagnosis of MN and hepatitis C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e2 (25.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber (%) of patients with, (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eRelapse\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e5 (62.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eIneffective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e3 (37.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious therapies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003ePrednisone + cyclophosphamide, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003ePrednisone + cyclosporine, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eTacrolimus, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"65.01831501831502%\"\u003e\n \u003cp\u003eMycophenolate mofetil, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.98168498168498%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003eData presented as median (first-third interquartile range) or mean \u0026plusmn; SD or number (percentage). RTX, rituximab; MN,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emembranous nephropathy; HCV, hepatitis C virus; BP, blood pressure; eGFR, estimated glomerular filtration rate; anti- PLA2R antibody, anti-phospholipase A2 receptor antibody.\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\n\u003cdiv align=\"center\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cp\u003eTable 2 Pathological characteristics of patients.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePLA2R staining\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eglomeruli\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eGlobally sclerotic glomeruli\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003eIFTA (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003eIgG4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eEM stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eSubepithelial Deposits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eIntramembranous Deposits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eSubendothelial Deposits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eMesangial Deposits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eTRIs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eHCV load at renal biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA\u0026plusmn;, IgM-, C3+，C4-，C1q-，FRA-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA\u0026plusmn;, IgM+, C3++，C4-，C1q-，FRA-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eII-III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA-, IgM+, C3+，C4\u0026plusmn;，C1q-，FRA-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG+++, IgA-, IgM+, C3+，C4-，C1q-，FRA－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eII-III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003e1.29\u0026times;10\u003csup\u003e6\u003c/sup\u003eIU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA-, IgM\u0026plusmn;, C3+，C4-，C1q-，FRA－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG+++, IgA-, IgM+, C3+，C4-，C1q-，FRA－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA\u0026plusmn;, IgM\u0026plusmn;, C3+，C4-，C1q-，FRA－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eII-III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\"\u003e\n \u003cp\u003e\u0026nbsp;IgG++, IgA-, IgM-, C3+，C4-，C1q-，FRA－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\"\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.446808510638298%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.1914893617021276%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;PLA2R, phospholipase A2 receptor; IFTA, interstitial fibrosis tubular atrophy; FRA, fibrin related antigen; EM, electron microscope; IF, immunofluorescence; HCV, hepatitis C virus; Neg, negative; Pos, positive.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"8\"\u003e\n \u003cp\u003eTable 3 Clinical findings in MN patients with hepatitis C.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003eCases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eTreatment of hepatitis C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eHepatitis C virus load at RTX infusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTime from identification of hepatitis C to renal biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eTime from identification of hepatitis C to RTX infusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eHepatitis C\u0026nbsp;occurred before/simultaneous MN diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eSofosbuvir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003ebefore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eSofosbuvir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003ebefore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eSofosbuvir\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003ebefore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eLedipasvir and Sofosbuvir Tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003esimultaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003ePeginterferon alfa-2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003ebefore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eElbasvir and Grazoprevir Tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003esimultaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eLedipasvir and Sofosbuvir Tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003ebefore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.208333333333333%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003eLedipasvir and Sofosbuvir Tablets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003eundetectable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.708333333333332%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\"\u003e\n \u003cp\u003esimultaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eTable 4 Efficacy outcome variables\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eMonth 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eLast visit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eRemission, complete and partial (N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e4 (50.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e6 (75.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e7 (87.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eRemission, complete (N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e2 (25.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e3 (37.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e5 (62.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eProteinuria (g/24h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e5.29 (3.53, 6.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e1.37 (0.46, 7.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e\u0026nbsp;1.10 (0.38, 1.85) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e0.62 (0.19, 0.91) \u003csup\u003ea,b,c\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eAlbumin (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e28.00 (25.05, 32.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e35.20 (30.70, 40.00) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e42.30 (32.00, 44.30) \u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e42.30 (38.90, 43.50) \u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eSerum creatinine (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e93.00 (79.00, 150.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e100.00 (89.25, 159.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e95.00 (85.50, 150.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e90.50 (83.00, 191.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eeGFR (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e71.10 (48.54, 89.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e55.83 (45.56, 86.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e65.27 (46.81, 73.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e67.24 (33.23, 79.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eanti-PLA2R-Ab\u0026ndash;positive patients (N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e4 (50.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e1 (12.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eanti-PLA2R-Ab\u0026ndash;depleted patients (N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e3 (37.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e6 (75.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eanti- PLA2R-Ab titer (RU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e34.20 (18.20, 85.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e6.60 (2.00, 18.00) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e\u0026nbsp;2.00 (2.00, 2.50) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e2.00 (2.00, 2.00) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003eCD19 (/mm\u003csup\u003e3\u003c/sup\u003e) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e292.00 (188.00, 327.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e13.00 (0.00, 87.50) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e22.00 (8.50, 190.50) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e235.00 (45.00, 298.00) \u003csup\u003ea\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.904847396768403%\"\u003e\n \u003cp\u003ePatients with\u0026nbsp;undetectable hepatitis C virus\u0026nbsp;(N, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.7737881508079%\"\u003e\n \u003cp\u003e8 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eData presented as number (percentage) or median (first-third interquartile range). \u003csup\u003ea\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eStands for p \u0026lt; 0.05 vs baseline; \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eStands for p \u0026lt; 0.05 vs month 6; \u003csup\u003ec\u0026nbsp;\u003c/sup\u003eStands for p \u0026lt; 0.05 vs month 12. eGFR, estimated glomerular filtration rate; anti-PLA2R-Ab, anti-phospholipase A2 receptor antibody; CD, Cluster of differentiation.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"PLA2R associated membranous nephropathy, phospholipase A2 receptor, HCV infection, rituximab","lastPublishedDoi":"10.21203/rs.3.rs-3974488/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3974488/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eRituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R) associated membranous nephropathy (MN). However, there is a lack of studies to report the effectiveness and safety of rituximab in patients with PLA2R associated MN and Hepatitis C virus (HCV) infection, which is the aim of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We performed a single center retrospective review of 8 consecutive PLA2R associated MN patients with HCV infection. We assessed clinical and laboratory indices, remission rates, and adverse events at rituximab infusion, month 6, month 12, and last visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 8 patients were enrolled, with a median follow-up period of 19.00 (16.00, 25.25) months. Of the 8 patients, 5 were male, and mean age was 50.13±4.29 years. At last visit, 5 (62.50%) patients achieved complete remission, and 7 (87.50%) patients achieved complete or partial remission. All 8 patients with HCV infection received antiviral agents and the load of HCV virus were undetectable at the time of rituximab treatment. No adverse effect of rituximab on HCV plasma viremia or hepatic transaminase levels was observed during the follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of rituximab in patients with PLA2R associated membranous nephropathy and HCV infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-14 19:49:35","doi":"10.21203/rs.3.rs-3974488/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-11T11:05:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-04T21:19:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137332971611599526013985802979636335789","date":"2024-05-21T06:22:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-16T11:04:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"366c98dc-9c88-47b8-becc-4e7ea56bd2bf","date":"2024-04-04T15:54:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"039535b0-6b87-4006-96fd-65c61d5f58c2","date":"2024-03-23T19:56:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34917baf-45af-49a6-b752-e592f4390a3d","date":"2024-03-23T12:56:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5db8cc6d-5b63-452c-83d5-5efb5da0515e","date":"2024-03-18T09:00:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-18T08:57:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-18T06:28:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-12T04:30:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-12T04:29:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-02-21T03:55:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1bb377f5-3fcc-47f1-95fa-a7d0ea5a5487","owner":[],"postedDate":"March 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-16T16:00:23+00:00","versionOfRecord":{"articleIdentity":"rs-3974488","link":"https://doi.org/10.1038/s41598-024-72082-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-09-09 15:57:13","publishedOnDateReadable":"September 9th, 2024"},"versionCreatedAt":"2024-03-14 19:49:35","video":"","vorDoi":"10.1038/s41598-024-72082-y","vorDoiUrl":"https://doi.org/10.1038/s41598-024-72082-y","workflowStages":[]},"version":"v1","identity":"rs-3974488","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3974488","identity":"rs-3974488","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}