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.