Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population

Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population Jung Woo Choi, Jin-Kyu Cho, Sang Soo Lee, Jae Heon Kim, Hankyu Jeon, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-181706/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failures and high short-term mortality. However, few studies reflecting the various etiologies of cirrhosis are available. We aimed to investigate the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods Between January 2005 and December 2018, 109 HCV-related cirrhosis patients who were hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and/or bacterial infection) were enrolled for ACLF defined by European Association for the Study of the Liver (EASL). Results ACLF developed in 35 patients (32.1%) on admission. Eight patients had ACLF grade 1, eight had ACLF grade 2, and 19 had ACLF grade 3. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%) compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF. Compared with all other prognostic scores, Chronic liver failure Consortium Organ Failure score most accurately predicted 90-day mortality, with an area under the receiver operator characteristic of 0.921. Conclusions HCV-related ACLF has unique clinical characteristics that are distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful in predicting short-term mortality in HCV-related cirrhosis. Infectious Diseases acute-on-chronic liver failure hepatitis C virus mortality organ failures acute decompensation. Figures Figure 1 Figure 2 Figure 3 Background Acute-on-chronic liver failure (ACLF) is a recently increasingly recognized syndrome in which acute decompensation (AD) leads to rapid liver and extra hepatic organ failure associated with high short-term mortality in patients with chronic liver disease [ 1 – 4 ]. Patients with ACLF have 28-day mortality rates of approximately 30% and 90-day mortality rates in exceeding 50% [ 5 – 7 ]. However, there is no diagnostic criteria for ACLF globally. Recently, two definitions of ACLF proposed by the Asian Pacific Association for the Study of the Liver (APASL) and the European Association for the Study of the Liver (EASL) are currently widely accepted. APASL-ACLF was defined first in 2009 as a rapid deterioration manifesting as jaundice (serum bilirubin ≥5 mg/dL) and coagulopathy (prolonged international normalized ratio (INR) ≥1.5) complicated by clinical ascites and/or hepatic encephalopathy (HE) in patients with previously known or unknown chronic liver disease [ 6 ]. In contrast, the EASL-ACLF, from the CANONIC study, was defined as AD (HE, gastrointestinal (GI) hemorrhage, ascites, or bacterial infection) in pre-existing cirrhosis patients followed by the development of multi-system organ failures [ 5 ]. Another important problem beyond the ongoing controversies surrounding diverse ACLF definitions is that the data that have been studied do not reflect the various causes of cirrhosis. The definition of APASL-ACLF was derived from a cohort consisting of patients predominantly infected by hepatitis B virus (HBV), whereas in the EASL-ACLF cohort, nearly 60% of patients had alcoholic liver disease. Subsequently, the Chinese Group on the Study of Severe Hepatitis B (COSSH) developed a new definition for HBV-related ACLF [ 8 ]. The Korean Acute-on-Chronic Liver Failure study cohort was proposed in cirrhosis patients from Korea, but this study had a population rate of alcoholic liver disease in excess of 60% [ 7 , 9 ]. Lee et al. recently investigated the ability of chronic liver failure sequential organ failure assessment (CLIF-SOFA) to predict short-term mortality in patients with alcohol-related ACLF [ 10 ]. However, to date, no studies have included patients with hepatitis C virus (HCV)-related ACLF. Therefore, we sought to identify the clinical features of patients of HCV-related ACLF in Korea, an HBV endemic area. Patients And Methods Study population This retrospective cohort study included 1743 patients with HCV infection who visited the Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital from January 2005 to December 2018. The exclusion criteria were as follows: (1) a follow-up period of less than 6 months (n = 273); (2) presence of hepatocellular carcinoma (n = 143); (3) presence of extrahepatic malignancy or severe extrahepatic disease (n = 37); (4) HBV co-infection (n = 53); (5) human immunodeficiency virus infection co-infection (n = 5); and (6) acute HCV infection (n = 10). Among the remaining 1222 patients with chronic hepatitis C, 1008 without cirrhosis and 214 with cirrhosis were initially analyzed for ACLF using the APASL criteria (total bilirubin ≥ 5 mg/dL and INR ≥ 1.5), applied to patients with chronic liver disease with or without cirrhosis. To apply the EASL-ACLF, after excluding 1008 patients without cirrhosis and 105 patients without AD events as defined by the acute development of overt ascites, HE, GI hemorrhage, and bacterial infection, 109 patients with cirrhosis who developed AD were finally analyzed (Fig. 1 ). The study was approved by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital. The need for informed consent was waived due to the retrospective design of this study, as determined by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital. Data collection and definition We collected data from the medical charts, including patient demographics, clinical and laboratory data on admission, types of AD events and organ failures, potential precipitating factors of AD and ACLF, and development of ACLF. Potential precipitating factors included bacterial infection, GI hemorrhage, active alcoholism, large volume paracentesis without albumin, transjugular intrahepatic portosystemic shunting, major surgery, hepatitis (including reactivation of viral hepatitis and toxic liver injury), and alcoholic hepatitis. Active alcoholism was defined as > 14 drinks per week in women and > 21 drinks per week in men within the last three months [ 5 ]. AD events were defined as acute onset of HE, ascites, GI hemorrhage, bacterial infection, or any combination of theses. Organ failure was defined according to a modified CLIF Consortium Organ Failure score (CLIF-C OFs) [ 11 ], which is a simplified modification of the CLIF-SOFA score and entails the following: liver failure, defined as total bilirubin level of ≥12 mg/dL; kidney failure, defined as serum creatinine level of ≥2.0 mg/dL and/or requiring renal replacement therapy; cerebral failure, defined as grade III or IV HE based on West Haven criteria; coagulation failure, defined as INR > 2.5; circulation failure, defined as treatment with vasoconstrictors to maintain the arterial blood pressure or inotropes to improve cardiac output; and respiratory failure, defined as PaO 2 /FiO 2 ≤ 200 or SpO 2 /FiO 2 ≤ 214. According to the EASL-ACLF criteria, the severity of ACLF was graded into ACLF grade 1 (ACLF-1), ACLF grade 2 (ACLF-2), or ACLF grade 3 (ACLF-3) according to the number of organ failures. ACLF-1 was defined by the presence of a single kidney failure or any other organ failure when in combination with either kidney dysfunction (serum creatinine ranging 1.5 to 1.9 mg/dL) or grade I or II HE. ACLF-2 or 3 was defined by the presence of 2 or ≥3 organ failures, respectively. We assessed the ACLF and ACLF grades, as defined above, by investigating for any association of organ failure at admission. Prognostic score The performance of CLIF-C OFs in evaluating prognosis was comparable to that of the CLIF-SOFA score [ 11 ]. To predict short-term mortality in cirrhosis patients with AD, we compared the performance of CLLF-C OFs with that of Child-Pugh-Turcotte (CTP) scores, model for end-stage liver disease (MELD) score and MELD-sodium (MELD-Na) score. In addition, the CLIF-C ACLF score (CLIF-C ACLFs) was used to predict short-term mortality in ACLF patients [ 11 ], and the CLIF-C AD score (CLIF-C ADs) was used in AD patients without ACLF [ 12 ]. Statistical analysis Fisher’s exact and Pearson’s chi-square tests to analyze the qualitative data and the Mann-Whitney U test to analyze the quantitative data were performed to assess the association between patient characteristics and ACLF at admission. Survival rates for the development of 90-day survival were estimated by the Kaplan-Meier method and compared using the log-rank test. The accuracy of the CLIF-OFs, CTP score, MELD score, and MELD-Na score in predicting survival was assessed by area under the receiver operating characteristic (AUROC) curve. A P -value < 0.05 was considered statistically significant for all analyses. All statistical operations were performed using PASW Statistics, version 18 (SPSS Inc., Chicago, IL, USA). Results Patient characteristics Patients with non-cirrhotic chronic hepatitis C did not exhibit ACLF as defined by APASL (total bilirubin ≥ 5 mg/dL and INR ≥ 1.5). Thus, the EASL-ACLF criteria were chosen to define ACLF in this study. The baseline characteristics of 109 patients with HCV-related cirrhosis are shown in Table 1 . Of cirrhosis patients with AD, ACLF developed in 35 patients (32.1%) on admission. Eight patients (7.3%) had ACLF-1, eight (7.3%) had ACLF-2, and 19 (17.4%) had ACLF-3. There was no significant difference in age, sex, HCV genotype, and sustained virologic response rate between patients with and without ACLF. Overt ascites was the most common type of AD, followed by bacterial infection, GI hemorrhage, and HE. GI hemorrhage, bacterial infection, and HE were more frequent in patients with ACLF than in patients without ACLF. History of AD was reported in 35 (32.1%) patients. Patients with ACLF more frequently had prior AD events. Table 1 Baseline characteristics of patients with HCV-related cirrhosis at admission according to ACLF Characteristics Overall (n = 109) No ACLF (n = 74) ACLF (n = 35) P Age, year 62.0 (53.0–71.5) 63.0 (53.0–72.3) 61.0 (51.0–70.0) 0.638 Male sex 65 (59.6%) 43 (58.1%) 22 (62.9%) 0.680 HCV genotype 0.594 1 50 (45.9%) 32 (43.2%) 18 (51.4%) 2 45 (41.3%) 33 (44.6%) 12 (34.3%) 3 14 (12.8%) 9 (12.2%) 5 (14.3%) SVR at enrollment 12 (11.0%) 7 (9.5%) 5 (14.3%) 0.517 Causes of hospitalization Ascites 50 (45.9%) 36 (48.6%) 14 (40.0%) 0.419 HE 24 (22.0%) 7 (9.5%) 17 (48.6%) < 0.001 GI hemorrhage 36 (33.0%) 30 (40.5%) 6 (17.1%) 0.017 Bacterial infection 37 (33.9%) 17 (23.0%) 20 (57.1%) 0.001 Precipitating events Bacterial infection 37 (33.9%) 17 (23.0%) 20 (57.1%) 0.001 GI hemorrhage 36 (33.0%) 30 (40.5%) 6 (17.1%) 0.017 Active alcoholism 11 (10.1%) 7 (9.5%) 4 (11.4%) 0.743 Other precipitating events 5 (4.6%) 1 (1.4%) 4 (11.4%) 0.036 No precipitating event 31 (28.4%) 24 (32.4%) 7 (20.0%) 0.256 More than one precipitating event 9 (8.3%) 4 (5.4%) 5 (14.3%) 0.143 Organ failure Liver 7 (6.4%) 1 (1.4%) 6 (17.1%) 0.004 Kidney 25 (22.9%) 0 25 (71.4%) < 0.001 Cerebral 26 (23.9%) 7 (9.5%) 19 (54.3%) < 0.001 Coagulation 12 (11.0%) 0 12 (34.3%) < 0.001 Circulation 19 (17.4%) 0 19 (54.3%) < 0.001 Respiration 17 (15.6%) 1 (1.4%) 16 (45.7%) < 0.001 Kidney dysfunction 8 (7.3%) 4 (5.4%) 4 (11.4%) 0.267 Time from first previous AD < 0.001 No previous AD 74 (67.9%) 59 (79.7%) 15 (42.9%) Less than 12 months 14 (12.8%) 7 (9.5%) 7 (20.0%) More than 12 months 21 (19.3%) 8 (10.8%) 13 (37.1%) Abbreviation:ACLF, acute on chronic liver failure; SVR, sustained virologic response; HE, Hepatic encephalopathy; GI, Gastrointestinal; AD, acute decompensation. P : Mann-Whitney U-test and Chi-squared test. Data are presented as the median (interquartile range) for continuous data and percentages for categorical data. On admission, patients with ACLF had higher median white blood cell, total bilirubin, creatinine, and INR levels but lower median albumin and sodium levels than those without ACLF (Table 2 ). Prognostic scores revealed that patients with ACLF had higher CTP scores, MELD scores, MELD-Na scores, and CLIF-OFs than those without ACLF. Table 2 Prognostic scores and laboratory data at admission Characteristics Overall (n = 109) No ACLF (n = 74) ACLF (n = 35) P Prognostic scores CTP 9.0 (7.0–11.0) 8.0 (7.0–10.0) 10.0 (8.0–12.0) < 0.001 MELD 14.0 (9.5–21.5) 11.0 (9.0–15.3) 26.0 (20.0–31.0) < 0.001 MELD-Na 18.0 (12.0–25.0) 14.5 (11.0–18.3) 28.0 (22.0–33.0) < 0.001 CLIF-C OFs 6.0 (6.0-8.5) 6.0 (6.0–6.0) 9.0 (12.0–14.0) < 0.001 CLIF-C ADs 48.0 (44.0–54.0) CLIF-C ACLFs 54.0 (46.0–61.0) Laboratory data WBC, 10 × 10 9 /L 6.3 (4.3–9.8) 5.7 (4.2–8.0) 9.4 (4.9–12.5) 0.005 Hemoglobin, g/dL 10.7 (8.8–12.3) 11.2 (8.8–12.7) 10.1 (8.6–11.8) 0.150 Platelet, ×10 9 /L 107.0 (67.0–136.5) 109.0 (70.0–139.5) 100.0 (54.0–127.0) 0.270 Bilirubin, mg/dL 1.6 (0.8–3.1) 1.3 (0.6–2.9) 2.4 (1.3–5.0) 0.001 AST, U/L 59.0 (38.0–96.0) 57.5 (37.8–84.5) 60.0 (38.0- 161.0) 0.345 ALT, U/L 35.0 (20.0–62.0) 35.0 (20.0–53.5) 28.0 (38.0–161.0) 0.820 Albumin, g/dL 2.7 (2.5–3.1) 2.9 (2.6–3.1) 2.5 (2.1–2.8) < 0.001 Creatinine, mg/dL 0.90 (0.69–1.64) 0.76 (0.62–0.90) 2.33 (1.69–2.96) < 0.001 Sodium, mmol/L 136.0 (132.0–139.4) 136.3 (133.4- 139.3) 133.2 (127.5–140.1) 0.045 PT-INR 1.42 (1.21–1.73) 1.31 (1.17–1.56) 1.81 (1.39–2.61) < 0.001 Abbreviation: ACLF, acute on chronic liver failure; CTP, Child-Turcotte-Pugh; MELD, model for end-stage liver disease; MELD-Na, model for end-stage liver disease-sodium; CLIF-C OFs, Chronic Liver Failure-Consortium Organ Failure Score; CLIP-C ADs, CLIF Consortium Acute Decompensation score; CLIP-C ACLFs, CLIF-Consortium scores for ACLF; WBC, white blood cell; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; PT-INR, prothrombin time- international normalized ratio. P : Mann-Whitney U-test and Chi-squared test. Data are presented as the median (interquartile range) for continuous data and percentages for categorical data. Organ failures and precipitating events Patients with ACLF more frequently had bacterial infection, GI hemorrhage, and a composite of other precipitating events than those without ACLF. No precipitating event was found in 28.4% of patients (Table 1 ). Skin infection (23.5%) was the most common type of bacterial infection, followed by pneumonia (17.6%), colitis (17.6%), spontaneous bacterial peritonitis (11.8%), urinary tract infection (11.8%), and unproved (5.9%) (Supplementary Table 1). The most common type of organ failure in patients with ACLF involved the kidney (71.4%), followed by the brain (54.3%), circulation (54.3%), the lungs (45.7%), coagulation (34.3%), and the liver (17.1%). Short-term mortality and prognostic scores Kaplan-Meier curves of the probability of survival revealed that patients with ACLF had poorer outcomes than those with AD (Fig. 2 A). Mortality at 28 days, 90 days, and 1 year for patients without ACLF was 2.7%, 5.4%, and 9.5%, respectively while mortality at 28 days, 90 days, and 1 year for patients with ACLF was 60.0%, 74.3%, and 80.0%, respectively (Fig. 2 B). Mortality at 28 days and 90 days was 2.7% and 5.4% for patients without ACLF, 0% and 37.5% for those with ACLF-1, 75.0% and 87.5% for those with ACLF-2, and 78.9% and 89.5% for those with ACLF-3, respectively (Supplementary Fig. 1). In the survival curve according to prior AD, there was a significant difference in the survival rates of patients with or without ACLF, but there was no significant difference in the survival rates of patients according to prior AD (Supplementary Fig. 2). Multiple organ failure without septic shock or hypovolemic shock was the most common cause of death at 90 days (53.3%), followed by septic shock (20.0%) and hypovolemic shock (16.7%) (Supplementary Table 2). Median CLIF-C ADs in patients without ACLF (n = 74) and CLIF-C ACLFs in patients with ACLF (n = 35) were 48.0 and 54.0, respectively. A strong stepwise association was observed between CLIF-C OFs and ACLF grades in cirrhosis patients with AD (Supplementary Fig. 3). Median CLIF-C OFs were 6.0, 7.5, 10.0, and 13.0 in patients without ACLF, ACLF-1, ACLF-2, and ACLF-3, respectively. All prognostic scores, including CTP score, MELD score, MELD-Na score, and CLIF-C OFs, were significantly higher in patients with ACLF than in those without ACLF (Table 2 ). In all patients (n = 109), median CLIF-C OFs were significantly higher in patients who died within 90 days than in those who did not die (12.0 vs. 6.0, P < 0.001) (Supplementary Fig. 4A). In patients without ACLF, there was no significant difference in median CLIF-ADs between patients who did and did not die (49.5 vs. 48.0, P = 0.881) (Supplementary Fig. 4B). In patients with ACLF, there was no significant difference in median CLIF-ACLFs between patients who did and did not die (54.0 vs. 47.0, P = 0.342). Among all prognostic parameters in all patients, CLIF-C OFs reveled the highest AUROC (0.921, 95% confidence interval [CI]: 0.855–0.986) for predicting 90-day mortality (Fig. 3 ). Meanwhile, ACLF, as defined by APASL, developed in ten patients (9.2%) at admission in 109 patients with AD and cirrhosis. Mortality at 28 days, 90 days, and 1 year for patients without APASL-ACLF was 17.2%, 21.2%, and 26.3%, respectively, while mortality at 28 days, 90 days, and 1 year for patients with APASL-ACLF was 60.0%, 90.0%, and 90.0%, respectively (Supplementary Fig. 5). Discussion In this study of 109 patients with HCV-related cirrhosis who were hospitalized for AD (ascites, HE, GI hemorrhage, and/or bacterial infection), 28-day and 90-day mortalities were higher in patients with ACLF at admission than in those without ACLF (60.0% and 74.3% vs. 2.7% and 5.4%, respectively). In addition, the CLIF-C OFs were the most accurate in predicting 90-day mortality for HCV-related cirrhosis patients who had AD compared with the CTP score, MELD score, and MELD-Na score. Among the various definitions of ACLF, no studies have been conducted in a cohort consisting only of patients with HCV-related chronic liver disease. In our chronic hepatitis C cohort of 1222 patients, no patient met the definition of APASL-ACLF (total bilirubin ≥5 mg/dL and INR ≥1.5) in patients without cirrhosis. There are very few episodes of acute flare-ups in chronic hepatitis C patients, even in immunocompromised patients.[ 13 ] Therefore, non-cirrhotic HCV-ACLF rarely occurs in chronic hepatitis C without cirrhosis, unlike in non-cirrhotic HBV-ACLF [ 8 , 14 , 15 ]. This suggests that the APASL-ACLF criteria or COSSH criteria cannot be applied to patients with non-cirrhotic chronic hepatitis C. Among 109 HCV-related cirrhosis patients, eight had EASL-ACLF and APASL-ACLF, 27 had EASL-ACLF alone, and two had APASL-ACLF alone. Therefore, the EASL-ACLF criteria detected more ACLF patients even in the setting of chronic hepatitis with cirrhosis. In a previous study using data from the Veterans Health Administration, the incidence of ACLF for patients with hepatitis C was higher in EASL-ACLF criteria than in APASL-ACLF [ 16 ]. In our study, patients with EASL-ACLF on admission had a significantly higher 90-day mortality rate than patients without EASL-ACLF. In particular, patients with ACLF-2 and ACLF-3 on admission had extremely high 90-day mortality (87.5% and 89.5%, respectively), while patients with no ACLF had very low 90-day mortality (5.4%). These suggest that EASL-ACLF is a very useful tool for predicting the prognosis in HCV–related cirrhosis patients who were hospitalized for acute deterioration. To our knowledge, our study is the first study on HCV-related ACLF that does not contain ACLF of other etiologies. HCV-related ACLF showed distinctive characteristics that distinguished ACLF from other causes. The 90-day mortality for patients ACLF was highest in our study, composed of HCV-related ACLF (74.3%), compared with the COSSH study (HBV-related ACLF, 69.7%),[ 8 ] the Korean study (alcohol-related ACLF, 67.2%) [ 10 ], and the CANONIC study, composed of various etiologies (51.2%) [ 5 ]. Comparing the prevalence of organ failure, liver failure in HCV-related ACLF was very low (17.1%) compared to HBV-related ACLF (93.7%) and the CANONIC study (43.6%) [ 5 , 8 ]. On the other hand, the prevalence of kidney failure in HCV-related ACLF was very high (71.4%) compared to that of HBV-related ACLF (14.0%) and the CANONIC study (55.8%). Therefore, ACLF in HCV-related cirrhosis may be associated with kidney failure rather than liver failure, which is thought to be associated with high short-term mortality. These suggest that the mechanism for HCV-ACLF probably reflects an extrahepatic insult, such as bacterial infection and GI hemorrhage, while the mechanism for HBV-ACLF probably reflects a hepatic insult, such as HBV flare. In a recent large-scale retrospective cohort study in the United States, patients with hepatitis C had the lowest ACLF incidence rate but had the highest short-term mortality compared with patients with HBV-related ACLF and alcohol-related ACLF [ 16 ]. CLIF-C OFs displayed the best prognostic ability for cirrhosis patients with AD (AUROC = 0.921, 95% CI 0.855–0.986) compared to the CTP score, MELD score, and MELD-Na score. CTP, MELD, and MELD-Na scores are based only on liver failure (bilirubin), kidney failure (creatinine), coagulation failure (INR), and cerebral failure (HE), whereas CLIF-C OFs additionally reflect coagulation and respiratory failure to predict the prognosis more effectively. The CLIF-SOFA score is a widely used tool in predicting short-term mortality in ACLF and AD patients and is superior to MELD score in predicting prognosis [ 10 , 14 , 17 , 18 ]. Our study showed that short-term mortality can be effectively predicted using CLIF-C OFs, a simplified modification of the CLIF-SOFA score. This study had some limitations. First, this was a retrospective study with a relatively small sample size. We were unable to accurately access HE grade 1 and 2 for measuring CLIF-C OFs through a retrospective chart review. Second, we excluded patients who were lost to follow-up within six months after transferring to other hospitals for liver transplantation because our institute cannot perform liver transplantation. Third, most HCV-infected patients in this study did not receive antiviral therapy because they were enrolled before the direct acting agent era or consisted of severe decompensated cirrhosis. Despite these limitations, the strength of our study is that it is the first study to identify the clinical features of patients HCV-related ACLF, especially in Korea, an HBV endemic area. Conclusion Applying the EASL-ACLF definition to patients with HCV-related cirrhosis can be useful in predicting short-term mortality, consistent with previous studies conducted on the other etiologies. Additionally, HCV-related ACLF has unique clinical features that are distinct from HBV-related or alcohol-related ACLF. Declarations Ethics approval and consent to participate The project was approved by the Institutional Review Board of Gyeongsang National University Changwon Hospital (IRB No. 2019-08-030) and Gyeongsang National University Hospital (IRB No. 2014-04-028). Informed consent was waived given that all of the personal data obtained were anonymized before analysis, as determined by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital. All methods in this study were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration. Consent for publication Not applicable. Availability of data and material The datasets generated and/or analyzed during the current study are not publicly available due to ethical and confidentiality reasons but are available from the corresponding author on reasonable request under the Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital Ethics Committee’s approval. The data that support the findings of this study are available on request to the correspondence author. (Sang Soo Lee, Email: [email protected] ) Competing interests The authors declare that they have no competing interests. Funding There was no financial support for this study. Authors’ Contributions: Conception and design: JWC, JKC, and SSL Data collection: JHK, HJ, HeeJK, RRC, JML, and HyunJK. Data analysis and interpretation: JWC, JKC, and SSL Manuscript writing: JWC and SSL Final approval of manuscript: All authors. Acknowledgements None. Writing Assistance: We would like to thank Editage (www.editage.co.kr) for English language editing. There was no financial support for writing assistance. References Arroyo V, Moreau R, Jalan R: Acute-on-Chronic Liver Failure. N Engl J Med 2020, 382(22):2137-45. Gustot T, Moreau R: Acute-on-chronic liver failure vs. traditional acute decompensation of cirrhosis. J Hepatol 2018, 69(6):1384-93. Hernaez R, Sola E, Moreau R, Gines P: Acute-on-chronic liver failure: an update. Gut 2017, 66(3):541-53. Bernal W, Jalan R, Quaglia A, Simpson K, Wendon J, Burroughs A: Acute-on-chronic liver failure. Lancet 2015, 386(10003):1576-87. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J et al: Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013, 144(7):1426-37, 37 e1-9. Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S et al: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019, 13(4):353-90. Kim TY, Song DS, Kim HY, Sinn DH, Yoon EL, Kim CW et al: Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition. PLoS One 2016, 11(1):e0146745. Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q et al: Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut 2018, 67(12):2181-91. Yoon EL, Kim TY, Lee CH, Kim TH, Cho HC, Lee SS et al: Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors. J Clin Gastroenterol 2019, 53(2):134-41. Lee M, Lee JH, Oh S, Jang Y, Lee W, Lee HJ et al: CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis. Liver Int 2015, 35(1):46-57. Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Gines P et al: Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014, 61(5):1038-47. Jalan R, Pavesi M, Saliba F, Amoros A, Fernandez J, Holland-Fischer P et al: The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015, 62(4):831-40. Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, Poynard T: Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 2006, 44(1 Suppl):S19-24. Li H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M et al: Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B. Sci Rep 2016, 6:25487. Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF: Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol 2018, 12(4):341-50. Mahmud N, Kaplan DE, Taddei TH, Goldberg DS: Incidence and Mortality of Acute-on-Chronic Liver Failure Using Two Definitions in Patients with Compensated Cirrhosis. Hepatology 2019, 69(5):2150-63. Engelmann C, Thomsen KL, Zakeri N, Sheikh M, Agarwal B, Jalan R, Mookerjee RP: Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure. Crit Care 2018, 22(1):254. Shin J, Yu JH, Jin YJ, Yim HJ, Jung YK, Yang JM et al: Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding. Clin Mol Hepatol 2020, 26(4):540-53. Supplementary Materials Supplementary Figure 1. Mortality at 28 days and 90 days according to grades of ACLF. Supplementary Figure 2. Survival curves in patients with or without ACLF according to prior acute decompensation. Supplementary Figure 3. CLIF-C OF score according to grades of ACLF. Supplementary Figure 4. Prognostic scores according to death. (A) CLIF-C OF scores in entire patients (n=109). (B) CLIF-C AD score in patients without ACLF (n=74). (C) CLIF-C ACLF score in patients with ACLF (n=35). Supplementary Figure 5. Mortality at 28 days and 90 days of patients with or without AARC-ACLF. Additional Declarations No competing interests reported. Supplementary Files Sup.fig.1.tif Sup.fig.2.tif Sup.fig.3.tif Sup.fig.4.tif Sup.fig.5.tif SupplementaryTables.docx Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-181706","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":11235811,"identity":"25ba0722-69f7-4f0f-a814-4880f90d1971","order_by":0,"name":"Jung Woo Choi","email":"","orcid":"","institution":"Gyeongsang National University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jung","middleName":"Woo","lastName":"Choi","suffix":""},{"id":11235812,"identity":"a9bb3e3a-6cf3-4990-92ee-904453d082ae","order_by":1,"name":"Jin-Kyu Cho","email":"","orcid":"","institution":"Gyeongsang National University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jin-Kyu","middleName":"","lastName":"Cho","suffix":""},{"id":11235813,"identity":"3f7dab03-2154-4f85-8fc5-02accd675c40","order_by":2,"name":"Sang Soo Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBACefb2gw8eMDDIEa/FsOdMskECA4MxCdbcSDCTAGpJbCBaB+OMhDSJhAqb9O3sZwwfVzDYyekS0szO8/CwRcKZtNydPTnGhmcYko3NDhCypT0h8UZi2+HcDQfS0iQbGA4kbiOkheFAgoFE4r//6Qbnn6X/JE7LiQQjicQGoMYbyccYidICCeRjyYYbbjw+LNlgQIRfwFH5ocZO3uB8YuPHhgo7OYJa0IABacpHwSgYBaNgFOAAAMrxR9Rn3RVPAAAAAElFTkSuQmCC","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Soo","lastName":"Lee","suffix":""},{"id":11235814,"identity":"c28df822-9606-49f4-8203-5e6101d132f8","order_by":3,"name":"Jae Heon Kim","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Heon","lastName":"Kim","suffix":""},{"id":11235815,"identity":"15b6720a-db54-4c96-bfe9-3b608aa4a8bc","order_by":4,"name":"Hankyu Jeon","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hankyu","middleName":"","lastName":"Jeon","suffix":""},{"id":11235816,"identity":"2a95823f-425c-4594-9d62-109679083bc4","order_by":5,"name":"Hee Jin Kim","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hee","middleName":"Jin","lastName":"Kim","suffix":""},{"id":11235817,"identity":"2685afcd-a698-4cd4-80fd-96725378f9d2","order_by":6,"name":"Ra Ri Cha","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ra","middleName":"Ri","lastName":"Cha","suffix":""},{"id":11235818,"identity":"8e113226-768f-4b5b-81a2-b835448c1d9f","order_by":7,"name":"Jae Min Lee","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Min","lastName":"Lee","suffix":""},{"id":11235819,"identity":"840061db-e52b-4fb1-968e-391e88c8634f","order_by":8,"name":"Hyun Jin Kim","email":"","orcid":"","institution":"Gyeongsang National University Changwon Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hyun","middleName":"Jin","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2021-01-29 05:14:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-181706/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-181706/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":5912779,"identity":"5897d6c9-78fa-4e3d-afb1-0691909e58f2","added_by":"auto","created_at":"2021-02-12 18:22:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":229822,"visible":true,"origin":"","legend":"Flow sheet ","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/3f18703ae64a4a1aaf483aee.jpg"},{"id":5912778,"identity":"debee81b-0def-4951-977b-2dafa860da26","added_by":"auto","created_at":"2021-02-12 18:22:41","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":260370,"visible":true,"origin":"","legend":"Prognosis according to ACLF. (A) Kaplan-Meier curves of the probability of survival within 28 days. (B) Mortality at 28 days, 90 days, and 1 year of patients without or with ACLF.","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/67e5b5b5a08276e7f9273934.jpg"},{"id":5912781,"identity":"23bafe42-6a19-4c69-b883-f823340893fc","added_by":"auto","created_at":"2021-02-12 18:22:42","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90365,"visible":true,"origin":"","legend":"Receiver operating characteristic curves of the CLIF-C OF score and three prognostic scoring systems in predicting 90-day mortality in HCV-related cirrhosis with acute decompensation (n=109).","description":"","filename":"Fig.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/cfb5b481af914ae0b27b2a59.jpg"},{"id":13661172,"identity":"668f2b84-7620-423c-887a-670319370642","added_by":"auto","created_at":"2021-09-17 10:28:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":531663,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/fbe3cafe-0adb-4d43-a032-5ffe6bf313ac.pdf"},{"id":5912268,"identity":"dfd527cd-67c2-4b16-a681-52eefd6252c0","added_by":"auto","created_at":"2021-02-12 18:19:41","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1545532,"visible":true,"origin":"","legend":"","description":"","filename":"Sup.fig.1.tif","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/cd2a9bc9c838082c7274198e.tif"},{"id":5912271,"identity":"218507e4-79c1-4a23-9266-d4ad9eb70ec6","added_by":"auto","created_at":"2021-02-12 18:19:41","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":2095416,"visible":true,"origin":"","legend":"","description":"","filename":"Sup.fig.2.tif","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/9c5dd3d8866ab562f27a1957.tif"},{"id":5912780,"identity":"757da90f-57e8-4068-8584-69ffc3d0462f","added_by":"auto","created_at":"2021-02-12 18:22:42","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":957564,"visible":true,"origin":"","legend":"","description":"","filename":"Sup.fig.3.tif","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/445823a0e65dfbafa378eef3.tif"},{"id":5912782,"identity":"0f36d1a8-f5df-49b9-ab56-9dd8239149cf","added_by":"auto","created_at":"2021-02-12 18:22:42","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":2098224,"visible":true,"origin":"","legend":"","description":"","filename":"Sup.fig.4.tif","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/b22d3454bc0ac2252fb80b99.tif"},{"id":5912273,"identity":"ea5b9598-f35c-4300-b01a-c8e41e602db0","added_by":"auto","created_at":"2021-02-12 18:19:42","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1638176,"visible":true,"origin":"","legend":"","description":"","filename":"Sup.fig.5.tif","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/1e4d7404e2437aec80cae3d7.tif"},{"id":5912274,"identity":"4ad20f0b-01d6-4c5f-a13c-9c81cd177144","added_by":"auto","created_at":"2021-02-12 18:19:42","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":17606,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-181706/v1/c44c760cdf643236e2d6cb2e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAcute-on-chronic liver failure (ACLF) is a recently increasingly recognized syndrome in which acute decompensation (AD) leads to rapid liver and extra hepatic organ failure associated with high short-term mortality in patients with chronic liver disease [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Patients with ACLF have 28-day mortality rates of approximately 30% and 90-day mortality rates in exceeding 50% [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, there is no diagnostic criteria for ACLF globally. Recently, two definitions of ACLF proposed by the Asian Pacific Association for the Study of the Liver (APASL) and the European Association for the Study of the Liver (EASL) are currently widely accepted. APASL-ACLF was defined first in 2009 as a rapid deterioration manifesting as jaundice (serum bilirubin \u0026ge;5 mg/dL) and coagulopathy (prolonged international normalized ratio (INR) \u0026ge;1.5) complicated by clinical ascites and/or hepatic encephalopathy (HE) in patients with previously known or unknown chronic liver disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In contrast, the EASL-ACLF, from the CANONIC study, was defined as AD (HE, gastrointestinal (GI) hemorrhage, ascites, or bacterial infection) in pre-existing cirrhosis patients followed by the development of multi-system organ failures [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAnother important problem beyond the ongoing controversies surrounding diverse ACLF definitions is that the data that have been studied do not reflect the various causes of cirrhosis. The definition of APASL-ACLF was derived from a cohort consisting of patients predominantly infected by hepatitis B virus (HBV), whereas in the EASL-ACLF cohort, nearly 60% of patients had alcoholic liver disease. Subsequently, the Chinese Group on the Study of Severe Hepatitis B (COSSH) developed a new definition for HBV-related ACLF [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The Korean Acute-on-Chronic Liver Failure study cohort was proposed in cirrhosis patients from Korea, but this study had a population rate of alcoholic liver disease in excess of 60% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Lee et al. recently investigated the ability of chronic liver failure sequential organ failure assessment (CLIF-SOFA) to predict short-term mortality in patients with alcohol-related ACLF [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, to date, no studies have included patients with hepatitis C virus (HCV)-related ACLF. Therefore, we sought to identify the clinical features of patients of HCV-related ACLF in Korea, an HBV endemic area.\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eThis retrospective cohort study included 1743 patients with HCV infection who visited the Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital from January 2005 to December 2018. The exclusion criteria were as follows: (1) a follow-up period of less than 6 months (n\u0026thinsp;=\u0026thinsp;273); (2) presence of hepatocellular carcinoma (n\u0026thinsp;=\u0026thinsp;143); (3) presence of extrahepatic malignancy or severe extrahepatic disease (n\u0026thinsp;=\u0026thinsp;37); (4) HBV co-infection (n\u0026thinsp;=\u0026thinsp;53); (5) human immunodeficiency virus infection co-infection (n\u0026thinsp;=\u0026thinsp;5); and (6) acute HCV infection (n\u0026thinsp;=\u0026thinsp;10). Among the remaining 1222 patients with chronic hepatitis C, 1008 without cirrhosis and 214 with cirrhosis were initially analyzed for ACLF using the APASL criteria (total bilirubin\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/dL and INR\u0026thinsp;\u0026ge;\u0026thinsp;1.5), applied to patients with chronic liver disease with or without cirrhosis. To apply the EASL-ACLF, after excluding 1008 patients without cirrhosis and 105 patients without AD events as defined by the acute development of overt ascites, HE, GI hemorrhage, and bacterial infection, 109 patients with cirrhosis who developed AD were finally analyzed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The study was approved by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital. The need for informed consent was waived due to the retrospective design of this study, as determined by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eData collection and definition\u003c/h2\u003e\u003cp\u003eWe collected data from the medical charts, including patient demographics, clinical and laboratory data on admission, types of AD events and organ failures, potential precipitating factors of AD and ACLF, and development of ACLF. Potential precipitating factors included bacterial infection, GI hemorrhage, active alcoholism, large volume paracentesis without albumin, transjugular intrahepatic portosystemic shunting, major surgery, hepatitis (including reactivation of viral hepatitis and toxic liver injury), and alcoholic hepatitis. Active alcoholism was defined as \u0026gt;\u0026thinsp;14 drinks per week in women and \u0026gt;\u0026thinsp;21 drinks per week in men within the last three months [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. AD events were defined as acute onset of HE, ascites, GI hemorrhage, bacterial infection, or any combination of theses. Organ failure was defined according to a modified CLIF Consortium Organ Failure score (CLIF-C OFs) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], which is a simplified modification of the CLIF-SOFA score and entails the following: liver failure, defined as total bilirubin level of \u0026ge;12 mg/dL; kidney failure, defined as serum creatinine level of \u0026ge;2.0 mg/dL and/or requiring renal replacement therapy; cerebral failure, defined as grade III or IV HE based on West Haven criteria; coagulation failure, defined as INR\u0026thinsp;\u0026gt;\u0026thinsp;2.5; circulation failure, defined as treatment with vasoconstrictors to maintain the arterial blood pressure or inotropes to improve cardiac output; and respiratory failure, defined as PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e \u0026le; 200 or SpO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e \u0026le; 214.\u003c/p\u003e\u003cp\u003eAccording to the EASL-ACLF criteria, the severity of ACLF was graded into ACLF grade 1 (ACLF-1), ACLF grade 2 (ACLF-2), or ACLF grade 3 (ACLF-3) according to the number of organ failures. ACLF-1 was defined by the presence of a single kidney failure or any other organ failure when in combination with either kidney dysfunction (serum creatinine ranging 1.5 to 1.9 mg/dL) or grade I or II HE. ACLF-2 or 3 was defined by the presence of 2 or \u0026ge;3 organ failures, respectively. We assessed the ACLF and ACLF grades, as defined above, by investigating for any association of organ failure at admission.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003ePrognostic score\u003c/h2\u003e\u003cp\u003eThe performance of CLIF-C OFs in evaluating prognosis was comparable to that of the CLIF-SOFA score [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. To predict short-term mortality in cirrhosis patients with AD, we compared the performance of CLLF-C OFs with that of Child-Pugh-Turcotte (CTP) scores, model for end-stage liver disease (MELD) score and MELD-sodium (MELD-Na) score. In addition, the CLIF-C ACLF score (CLIF-C ACLFs) was used to predict short-term mortality in ACLF patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and the CLIF-C AD score (CLIF-C ADs) was used in AD patients without ACLF [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eFisher\u0026rsquo;s exact and Pearson\u0026rsquo;s chi-square tests to analyze the qualitative data and the Mann-Whitney U test to analyze the quantitative data were performed to assess the association between patient characteristics and ACLF at admission. Survival rates for the development of 90-day survival were estimated by the Kaplan-Meier method and compared using the log-rank test. The accuracy of the CLIF-OFs, CTP score, MELD score, and MELD-Na score in predicting survival was assessed by area under the receiver operating characteristic (AUROC) curve. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for all analyses. All statistical operations were performed using PASW Statistics, version 18 (SPSS Inc., Chicago, IL, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003ePatient characteristics\u003c/h2\u003e\n\u003cp\u003ePatients with non-cirrhotic chronic hepatitis C did not exhibit ACLF as defined by APASL (total bilirubin\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/dL and INR\u0026thinsp;\u0026ge;\u0026thinsp;1.5). Thus, the EASL-ACLF criteria were chosen to define ACLF in this study. The baseline characteristics of 109 patients with HCV-related cirrhosis are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Of cirrhosis patients with AD, ACLF developed in 35 patients (32.1%) on admission. Eight patients (7.3%) had ACLF-1, eight (7.3%) had ACLF-2, and 19 (17.4%) had ACLF-3. There was no significant difference in age, sex, HCV genotype, and sustained virologic response rate between patients with and without ACLF. Overt ascites was the most common type of AD, followed by bacterial infection, GI hemorrhage, and HE. GI hemorrhage, bacterial infection, and HE were more frequent in patients with ACLF than in patients without ACLF. History of AD was reported in 35 (32.1%) patients. Patients with ACLF more frequently had prior AD events.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline characteristics of patients with HCV-related cirrhosis at admission according to ACLF\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;109)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNo ACLF (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eACLF (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eAge, year\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e62.0 (53.0\u0026ndash;71.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e63.0 (53.0\u0026ndash;72.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e61.0 (51.0\u0026ndash;70.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.638\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMale sex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e65 (59.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e43 (58.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e22 (62.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.680\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eHCV genotype\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.594\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e50 (45.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e32 (43.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e18 (51.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e45 (41.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e33 (44.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (34.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e14 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e9 (12.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eSVR at enrollment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (11.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7 (9.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.517\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCauses of hospitalization\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eAscites\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e50 (45.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e36 (48.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e14 (40.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.419\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eHE\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e24 (22.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7 (9.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e17 (48.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eGI hemorrhage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e36 (33.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e30 (40.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e6 (17.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eBacterial infection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e37 (33.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e17 (23.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e20 (57.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ePrecipitating events\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eBacterial infection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e37 (33.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e17 (23.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e20 (57.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eGI hemorrhage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e36 (33.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e30 (40.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e6 (17.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eActive alcoholism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e11 (10.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7 (9.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (11.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.743\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eOther precipitating events\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (4.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1 (1.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (11.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.036\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNo precipitating event\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e31 (28.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e24 (32.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (20.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.256\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMore than one precipitating event\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e9 (8.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4 (5.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e5 (14.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eOrgan failure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eLiver\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (6.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1 (1.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e6 (17.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eKidney\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e25 (22.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e25 (71.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCerebral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e26 (23.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7 (9.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e19 (54.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCoagulation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (11.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e12 (34.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eCirculation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e19 (17.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e19 (54.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eRespiration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e17 (15.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e1 (1.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e16 (45.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eKidney dysfunction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e8 (7.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e4 (5.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e4 (11.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.267\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eTime from first previous AD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eNo previous AD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e74 (67.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e59 (79.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e15 (42.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eLess than 12 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e14 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e7 (9.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e7 (20.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMore than 12 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e21 (19.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e8 (10.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e13 (37.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr style=\"height: 13px;\"\u003e\n\u003ctd style=\"height: 13px;\" colspan=\"5\"\u003eAbbreviation:ACLF, acute on chronic liver failure; SVR, sustained virologic response; HE, Hepatic encephalopathy; GI, Gastrointestinal; AD, acute decompensation.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 13.375px;\"\u003e\n\u003ctd style=\"height: 13.375px;\" colspan=\"5\"\u003e\u003cem\u003eP\u003c/em\u003e: Mann-Whitney U-test and Chi-squared test.\n\u003cp\u003eData are presented as the median (interquartile range) for continuous data and percentages for categorical data.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOn admission, patients with ACLF had higher median white blood cell, total bilirubin, creatinine, and INR levels but lower median albumin and sodium levels than those without ACLF (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Prognostic scores revealed that patients with ACLF had higher CTP scores, MELD scores, MELD-Na scores, and CLIF-OFs than those without ACLF.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePrognostic scores and laboratory data at admission\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;109)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo ACLF (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eACLF (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrognostic scores\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCTP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.0 (7.0\u0026ndash;11.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.0 (7.0\u0026ndash;10.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.0 (8.0\u0026ndash;12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMELD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14.0 (9.5\u0026ndash;21.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.0 (9.0\u0026ndash;15.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26.0 (20.0\u0026ndash;31.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMELD-Na\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18.0 (12.0\u0026ndash;25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14.5 (11.0\u0026ndash;18.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e28.0 (22.0\u0026ndash;33.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCLIF-C OFs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.0 (6.0-8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.0 (6.0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.0 (12.0\u0026ndash;14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCLIF-C ADs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e48.0 (44.0\u0026ndash;54.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCLIF-C ACLFs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e54.0 (46.0\u0026ndash;61.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLaboratory data\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWBC, \u003cem\u003e10\u003c/em\u003e \u0026times; \u003cem\u003e10\u003c/em\u003e\u003csup\u003e\u003cem\u003e9\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e/L\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.3 (4.3\u0026ndash;9.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.7 (4.2\u0026ndash;8.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.4 (4.9\u0026ndash;12.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin, \u003cem\u003eg/dL\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.7 (8.8\u0026ndash;12.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.2 (8.8\u0026ndash;12.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.1 (8.6\u0026ndash;11.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.150\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePlatelet, \u003cem\u003e\u0026times;10\u003c/em\u003e\u003csup\u003e\u003cem\u003e9\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e/L\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e107.0 (67.0\u0026ndash;136.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e109.0 (70.0\u0026ndash;139.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e100.0 (54.0\u0026ndash;127.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.270\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilirubin, \u003cem\u003emg/dL\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.6 (0.8\u0026ndash;3.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.3 (0.6\u0026ndash;2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.4 (1.3\u0026ndash;5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST, \u003cem\u003eU/L\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e59.0 (38.0\u0026ndash;96.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e57.5 (37.8\u0026ndash;84.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e60.0 (38.0- 161.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.345\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT, \u003cem\u003eU/L\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e35.0 (20.0\u0026ndash;62.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e35.0 (20.0\u0026ndash;53.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e28.0 (38.0\u0026ndash;161.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.820\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlbumin, \u003cem\u003eg/dL\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.7 (2.5\u0026ndash;3.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.9 (2.6\u0026ndash;3.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.5 (2.1\u0026ndash;2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCreatinine, \u003cem\u003emg/dL\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.90 (0.69\u0026ndash;1.64)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.76 (0.62\u0026ndash;0.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.33 (1.69\u0026ndash;2.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSodium, \u003cem\u003emmol/L\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e136.0 (132.0\u0026ndash;139.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e136.3 (133.4- 139.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e133.2 (127.5\u0026ndash;140.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.045\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT-INR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.42 (1.21\u0026ndash;1.73)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.31 (1.17\u0026ndash;1.56)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.81 (1.39\u0026ndash;2.61)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\n\u003cp\u003eAbbreviation: ACLF, acute on chronic liver failure; CTP, Child-Turcotte-Pugh; MELD, model for end-stage liver disease; MELD-Na, model for end-stage liver disease-sodium; CLIF-C OFs, Chronic Liver Failure-Consortium Organ Failure Score; CLIP-C ADs, CLIF Consortium Acute Decompensation score; CLIP-C ACLFs, CLIF-Consortium scores for ACLF; WBC, white blood cell; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; PT-INR, prothrombin time- international normalized ratio.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e: Mann-Whitney U-test and Chi-squared test.\u003c/p\u003e\n\u003cp\u003eData are presented as the median (interquartile range) for continuous data and percentages for categorical data.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eOrgan failures and precipitating events\u003c/h2\u003e\n\u003cp\u003ePatients with ACLF more frequently had bacterial infection, GI hemorrhage, and a composite of other precipitating events than those without ACLF. No precipitating event was found in 28.4% of patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Skin infection (23.5%) was the most common type of bacterial infection, followed by pneumonia (17.6%), colitis (17.6%), spontaneous bacterial peritonitis (11.8%), urinary tract infection (11.8%), and unproved (5.9%) (Supplementary Table\u0026nbsp;1). The most common type of organ failure in patients with ACLF involved the kidney (71.4%), followed by the brain (54.3%), circulation (54.3%), the lungs (45.7%), coagulation (34.3%), and the liver (17.1%).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003eShort-term mortality and prognostic scores\u003c/h2\u003e\n\u003cp\u003eKaplan-Meier curves of the probability of survival revealed that patients with ACLF had poorer outcomes than those with AD (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). Mortality at 28 days, 90 days, and 1 year for patients without ACLF was 2.7%, 5.4%, and 9.5%, respectively while mortality at 28 days, 90 days, and 1 year for patients with ACLF was 60.0%, 74.3%, and 80.0%, respectively (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). Mortality at 28 days and 90 days was 2.7% and 5.4% for patients without ACLF, 0% and 37.5% for those with ACLF-1, 75.0% and 87.5% for those with ACLF-2, and 78.9% and 89.5% for those with ACLF-3, respectively (Supplementary Fig.\u0026nbsp;1). In the survival curve according to prior AD, there was a significant difference in the survival rates of patients with or without ACLF, but there was no significant difference in the survival rates of patients according to prior AD (Supplementary Fig.\u0026nbsp;2). Multiple organ failure without septic shock or hypovolemic shock was the most common cause of death at 90 days (53.3%), followed by septic shock (20.0%) and hypovolemic shock (16.7%) (Supplementary Table\u0026nbsp;2).\u003c/p\u003e\n\u003cp\u003eMedian CLIF-C ADs in patients without ACLF (n\u0026thinsp;=\u0026thinsp;74) and CLIF-C ACLFs in patients with ACLF (n\u0026thinsp;=\u0026thinsp;35) were 48.0 and 54.0, respectively. A strong stepwise association was observed between CLIF-C OFs and ACLF grades in cirrhosis patients with AD (Supplementary Fig.\u0026nbsp;3). Median CLIF-C OFs were 6.0, 7.5, 10.0, and 13.0 in patients without ACLF, ACLF-1, ACLF-2, and ACLF-3, respectively. All prognostic scores, including CTP score, MELD score, MELD-Na score, and CLIF-C OFs, were significantly higher in patients with ACLF than in those without ACLF (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). In all patients (n\u0026thinsp;=\u0026thinsp;109), median CLIF-C OFs were significantly higher in patients who died within 90 days than in those who did not die (12.0 vs. 6.0, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Supplementary Fig.\u0026nbsp;4A). In patients without ACLF, there was no significant difference in median CLIF-ADs between patients who did and did not die (49.5 vs. 48.0, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.881) (Supplementary Fig.\u0026nbsp;4B). In patients with ACLF, there was no significant difference in median CLIF-ACLFs between patients who did and did not die (54.0 vs. 47.0, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.342). Among all prognostic parameters in all patients, CLIF-C OFs reveled the highest AUROC (0.921, 95% confidence interval [CI]: 0.855\u0026ndash;0.986) for predicting 90-day mortality (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eMeanwhile, ACLF, as defined by APASL, developed in ten patients (9.2%) at admission in 109 patients with AD and cirrhosis. Mortality at 28 days, 90 days, and 1 year for patients without APASL-ACLF was 17.2%, 21.2%, and 26.3%, respectively, while mortality at 28 days, 90 days, and 1 year for patients with APASL-ACLF was 60.0%, 90.0%, and 90.0%, respectively (Supplementary Fig.\u0026nbsp;5).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study of 109 patients with HCV-related cirrhosis who were hospitalized for AD (ascites, HE, GI hemorrhage, and/or bacterial infection), 28-day and 90-day mortalities were higher in patients with ACLF at admission than in those without ACLF (60.0% and 74.3% vs. 2.7% and 5.4%, respectively). In addition, the CLIF-C OFs were the most accurate in predicting 90-day mortality for HCV-related cirrhosis patients who had AD compared with the CTP score, MELD score, and MELD-Na score.\u003c/p\u003e\u003cp\u003eAmong the various definitions of ACLF, no studies have been conducted in a cohort consisting only of patients with HCV-related chronic liver disease. In our chronic hepatitis C cohort of 1222 patients, no patient met the definition of APASL-ACLF (total bilirubin \u0026ge;5 mg/dL and INR \u0026ge;1.5) in patients without cirrhosis. There are very few episodes of acute flare-ups in chronic hepatitis C patients, even in immunocompromised patients.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Therefore, non-cirrhotic HCV-ACLF rarely occurs in chronic hepatitis C without cirrhosis, unlike in non-cirrhotic HBV-ACLF [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This suggests that the APASL-ACLF criteria or COSSH criteria cannot be applied to patients with non-cirrhotic chronic hepatitis C. Among 109 HCV-related cirrhosis patients, eight had EASL-ACLF and APASL-ACLF, 27 had EASL-ACLF alone, and two had APASL-ACLF alone. Therefore, the EASL-ACLF criteria detected more ACLF patients even in the setting of chronic hepatitis with cirrhosis. In a previous study using data from the Veterans Health Administration, the incidence of ACLF for patients with hepatitis C was higher in EASL-ACLF criteria than in APASL-ACLF [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In our study, patients with EASL-ACLF on admission had a significantly higher 90-day mortality rate than patients without EASL-ACLF. In particular, patients with ACLF-2 and ACLF-3 on admission had extremely high 90-day mortality (87.5% and 89.5%, respectively), while patients with no ACLF had very low 90-day mortality (5.4%). These suggest that EASL-ACLF is a very useful tool for predicting the prognosis in HCV\u0026ndash;related cirrhosis patients who were hospitalized for acute deterioration. To our knowledge, our study is the first study on HCV-related ACLF that does not contain ACLF of other etiologies.\u003c/p\u003e\u003cp\u003eHCV-related ACLF showed distinctive characteristics that distinguished ACLF from other causes. The 90-day mortality for patients ACLF was highest in our study, composed of HCV-related ACLF (74.3%), compared with the COSSH study (HBV-related ACLF, 69.7%),[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] the Korean study (alcohol-related ACLF, 67.2%) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and the CANONIC study, composed of various etiologies (51.2%) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Comparing the prevalence of organ failure, liver failure in HCV-related ACLF was very low (17.1%) compared to HBV-related ACLF (93.7%) and the CANONIC study (43.6%) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. On the other hand, the prevalence of kidney failure in HCV-related ACLF was very high (71.4%) compared to that of HBV-related ACLF (14.0%) and the CANONIC study (55.8%). Therefore, ACLF in HCV-related cirrhosis may be associated with kidney failure rather than liver failure, which is thought to be associated with high short-term mortality. These suggest that the mechanism for HCV-ACLF probably reflects an extrahepatic insult, such as bacterial infection and GI hemorrhage, while the mechanism for HBV-ACLF probably reflects a hepatic insult, such as HBV flare. In a recent large-scale retrospective cohort study in the United States, patients with hepatitis C had the lowest ACLF incidence rate but had the highest short-term mortality compared with patients with HBV-related ACLF and alcohol-related ACLF [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCLIF-C OFs displayed the best prognostic ability for cirrhosis patients with AD (AUROC\u0026thinsp;=\u0026thinsp;0.921, 95% CI 0.855\u0026ndash;0.986) compared to the CTP score, MELD score, and MELD-Na score. CTP, MELD, and MELD-Na scores are based only on liver failure (bilirubin), kidney failure (creatinine), coagulation failure (INR), and cerebral failure (HE), whereas CLIF-C OFs additionally reflect coagulation and respiratory failure to predict the prognosis more effectively. The CLIF-SOFA score is a widely used tool in predicting short-term mortality in ACLF and AD patients and is superior to MELD score in predicting prognosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Our study showed that short-term mortality can be effectively predicted using CLIF-C OFs, a simplified modification of the CLIF-SOFA score.\u003c/p\u003e\u003cp\u003eThis study had some limitations. First, this was a retrospective study with a relatively small sample size. We were unable to accurately access HE grade 1 and 2 for measuring CLIF-C OFs through a retrospective chart review. Second, we excluded patients who were lost to follow-up within six months after transferring to other hospitals for liver transplantation because our institute cannot perform liver transplantation. Third, most HCV-infected patients in this study did not receive antiviral therapy because they were enrolled before the direct acting agent era or consisted of severe decompensated cirrhosis. Despite these limitations, the strength of our study is that it is the first study to identify the clinical features of patients HCV-related ACLF, especially in Korea, an HBV endemic area.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eApplying the EASL-ACLF definition to patients with HCV-related cirrhosis can be useful in predicting short-term mortality, consistent with previous studies conducted on the other etiologies. Additionally, HCV-related ACLF has unique clinical features that are distinct from HBV-related or alcohol-related ACLF.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe project was approved by the Institutional Review Board of Gyeongsang National University Changwon Hospital (IRB No. 2019-08-030) and Gyeongsang National University Hospital (IRB No. 2014-04-028). Informed consent was waived given that all of the personal data obtained were anonymized before analysis, as determined by the Institutional Review Boards of Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital. All methods in this study were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to ethical and confidentiality reasons but are available from the corresponding author on reasonable request under the Gyeongsang National University Changwon Hospital and Gyeongsang National University Hospital Ethics Committee\u0026rsquo;s approval. The data that support the findings of this study are available on request to the correspondence author. (Sang Soo Lee, Email:[email protected])\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no financial support for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions: \u003c/strong\u003eConception and design: JWC, JKC, and SSL\u003c/p\u003e\n\u003cp\u003eData collection: JHK, HJ, HeeJK, RRC, JML, and HyunJK.\u003c/p\u003e\n\u003cp\u003eData analysis and interpretation: JWC, JKC, and SSL\u003c/p\u003e\n\u003cp\u003eManuscript writing: JWC and SSL\u003c/p\u003e\n\u003cp\u003eFinal approval of manuscript: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting Assistance: \u003c/strong\u003eWe would like to thank Editage (www.editage.co.kr) for English language editing. There was no financial support for writing assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eArroyo V, Moreau R, Jalan R: Acute-on-Chronic Liver Failure. N Engl J Med 2020, 382(22):2137-45.\u003c/li\u003e\n\u003cli\u003eGustot T, Moreau R: Acute-on-chronic liver failure vs. traditional acute decompensation of cirrhosis. J Hepatol 2018, 69(6):1384-93.\u003c/li\u003e\n\u003cli\u003eHernaez R, Sola E, Moreau R, Gines P: Acute-on-chronic liver failure: an update. Gut 2017, 66(3):541-53.\u003c/li\u003e\n\u003cli\u003eBernal W, Jalan R, Quaglia A, Simpson K, Wendon J, Burroughs A: Acute-on-chronic liver failure. Lancet 2015, 386(10003):1576-87.\u003c/li\u003e\n\u003cli\u003eMoreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J et al: Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013, 144(7):1426-37, 37 e1-9.\u003c/li\u003e\n\u003cli\u003eSarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S et al: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019, 13(4):353-90.\u003c/li\u003e\n\u003cli\u003eKim TY, Song DS, Kim HY, Sinn DH, Yoon EL, Kim CW et al: Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition. PLoS One 2016, 11(1):e0146745.\u003c/li\u003e\n\u003cli\u003eWu T, Li J, Shao L, Xin J, Jiang L, Zhou Q et al: Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut 2018, 67(12):2181-91.\u003c/li\u003e\n\u003cli\u003eYoon EL, Kim TY, Lee CH, Kim TH, Cho HC, Lee SS et al: Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors. J Clin Gastroenterol 2019, 53(2):134-41.\u003c/li\u003e\n\u003cli\u003eLee M, Lee JH, Oh S, Jang Y, Lee W, Lee HJ et al: CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis. Liver Int 2015, 35(1):46-57.\u003c/li\u003e\n\u003cli\u003eJalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Gines P et al: Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014, 61(5):1038-47.\u003c/li\u003e\n\u003cli\u003eJalan R, Pavesi M, Saliba F, Amoros A, Fernandez J, Holland-Fischer P et al: The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015, 62(4):831-40.\u003c/li\u003e\n\u003cli\u003eMassard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, Poynard T: Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 2006, 44(1 Suppl):S19-24.\u003c/li\u003e\n\u003cli\u003eLi H, Chen LY, Zhang NN, Li ST, Zeng B, Pavesi M et al: Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B. Sci Rep 2016, 6:25487.\u003c/li\u003e\n\u003cli\u003eZhao RH, Shi Y, Zhao H, Wu W, Sheng JF: Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol 2018, 12(4):341-50.\u003c/li\u003e\n\u003cli\u003eMahmud N, Kaplan DE, Taddei TH, Goldberg DS: Incidence and Mortality of Acute-on-Chronic Liver Failure Using Two Definitions in Patients with Compensated Cirrhosis. Hepatology 2019, 69(5):2150-63.\u003c/li\u003e\n\u003cli\u003eEngelmann C, Thomsen KL, Zakeri N, Sheikh M, Agarwal B, Jalan R, Mookerjee RP: Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure. Crit Care 2018, 22(1):254.\u003c/li\u003e\n\u003cli\u003eShin J, Yu JH, Jin YJ, Yim HJ, Jung YK, Yang JM et al: Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding. Clin Mol Hepatol 2020, 26(4):540-53.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Supplementary Materials","content":"\u003cp\u003eSupplementary Figure 1. Mortality at 28 days and 90 days according to grades of ACLF.\u003c/p\u003e\n\u003cp\u003eSupplementary Figure 2. Survival curves in patients with or without ACLF according to prior acute decompensation.\u003c/p\u003e\n\u003cp\u003eSupplementary Figure 3. CLIF-C OF score according to grades of ACLF.\u003c/p\u003e\n\u003cp\u003eSupplementary Figure 4. Prognostic scores according to death. (A) CLIF-C OF scores in entire patients (n=109). (B) CLIF-C AD score in patients without ACLF (n=74). (C) CLIF-C ACLF score in patients with ACLF (n=35).\u003c/p\u003e\n\u003cp\u003eSupplementary Figure 5. Mortality at 28 days and 90 days of patients with or without AARC-ACLF.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute-on-chronic liver failure, hepatitis C virus, mortality, organ failures, acute decompensation.","lastPublishedDoi":"10.21203/rs.3.rs-181706/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-181706/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failures and high short-term mortality. However, few studies reflecting the various etiologies of cirrhosis are available. We aimed to investigate the clinical features of patients with hepatitis C virus (HCV)-related ACLF.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBetween January 2005 and December 2018, 109 HCV-related cirrhosis patients who were hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and/or bacterial infection) were enrolled for ACLF defined by European Association for the Study of the Liver (EASL).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eACLF developed in 35 patients (32.1%) on admission. Eight patients had ACLF grade 1, eight had ACLF grade 2, and 19 had ACLF grade 3. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%) compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF. Compared with all other prognostic scores, Chronic liver failure Consortium Organ Failure score most accurately predicted 90-day mortality, with an area under the receiver operator characteristic of 0.921.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHCV-related ACLF has unique clinical characteristics that are distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful in predicting short-term mortality in HCV-related cirrhosis.\u003c/p\u003e","manuscriptTitle":"Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-12 18:19:39","doi":"10.21203/rs.3.rs-181706/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"433dd396-d829-46eb-a06b-1251c23dcec7","owner":[],"postedDate":"February 12th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2383910,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2021-03-19T03:44:07+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-12 18:19:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-181706","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-181706","identity":"rs-181706","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}