Elevated liver enzymes predict morbidity and mortality despite antiviral cure in patients with chronic hepatitis C: Data from the German Hepatitis C‐Registry

Abstract

While direct‐acting antivirals (DAAs) cure chronic hepatitis C virus (HCV) infection in almost all patients, some patients remain at risk of liver disease despite HCV cure. In order to identify risk factors indicating liver‐related morbidity and death after viral cure, we included 6982 patients from the national multicenter real‐world German Hepatitis C Registry with regular follow‐up visits for up to 7 years after DAA therapy. Definitions for normal liver function tests (in women/men) were alanine aminotransferase (ALT; ≤35/≤50 U/L), ALT according to American Association for the Study of Liver Diseases (AASLD; ≤19/≤30 U/L), and gamma‐glutamyltransferase (GGT; ≤40/≤60 U/L). In our cohort, 97.4% of patients achieved sustained virologic response (SVR). At 24 weeks after SVR (SVR24), elevated ALT occurred in 657/6982 (9.4%), elevated ALT (AASLD) in 2609/6982 (37.4%), and elevated GGT in 1777/6982 (25.5%) patients. Risk factors for increased ALT at SVR24 were obesity, alcohol, cirrhosis, elevated baseline ALT, and non‐SVR. Increased GGT at SVR24 was significantly ( p < 0.05) and independently associated with male sex (odds ratio [OR], 2.12), higher body mass index (OR, 1.04), age >50 years (OR, 1.60), liver cirrhosis (OR, 3.97), alcohol consumption (OR, 2.99), diabetes (OR, 1.63), non‐SVR (OR, 8.00), and elevated GGT at baseline (OR, 17.12). In multivariate regression analysis, elevated GGT at SVR24, particularly in combination with cirrhosis, was the best predictor for hepatic decompensation, hepatocellular carcinoma development, and death, followed by elevated ALT (AASLD) and standard ALT, which predicted hepatic decompensation. Despite successful HCV therapy, elevated GGT at SVR24 and to a lesser extent ALT are predictive of the future clinical outcome and linked with liver‐associated comorbidities. This may highlight the relevance of nonalcoholic fatty liver disease, diabetes mellitus, alcohol, and cirrhosis for the clinical outcome in a vulnerable population, even after HCV cure.

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis—New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases

“…NASH determines asymptomatic elevation of ALT and AST levels in up to 90% of cases, once other liver disease causes are excluded [28]. Numerous studies have shown that serum levels of ALT and AST are elevated in CHC patients in different stages of the disease [29,30]. In this study, AST and ALT levels were significantly higher in all liver disease groups in comparison with CG.…”

High prevalence of fatty liver and its association with metabolic syndrome among rural adults with chronic hepatitis C: Implications for primary healthcare

“…Considering the new era of CHC therapy via Direct-Acting antivirals(DAAs), DAAs are associated with > 95% cure rate and reduction in risk of developing HCC and are significantly beneficial in reducing diabetes mellitus, the levels of liver enzymes (GOT, GPT, and GGT) [ 33 , 35 ], and the severity of fatty liver disease[ 36 ]. Hence, eradication of CHC through DAAs therapy may prevent adverse outcomes of cirrhosis and HCC and is potentially beneficial for the regression of fatty liver and control of diabetes mellitus.…”

Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals

“…The present findings showed the importance for the combination of three factors including gender, FIB-4 index, and GGT. Furthermore, the present results suggested the importance of GGT as one of metabolic surrogate markers, including metabolic disorder, alcohol consumption, and fatty liver disease [ 11 ]. Recently, an international expert panel proposed a new definition of fatty liver, metabolic dysfunction-associated fatty liver (MAFLD).…”