Liver Steatosis Is a Major Predictor of Poor Outcomes in Chronic Hepatitis C Patients With Sustained Virological Response

Noam Peleg; Assaf Issachar; Orly Sneh Arbib; Michal Cohen-Naftaly; Yael Harif; Evelin Oxtrud; Marius Braun; Moshe Leshno; Alon Barsheshet; Amir Shlomai


J Viral Hepat. 2019;26(11):1257-1265. 

In This Article

Abstract and Introduction


Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61–13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97–6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.


Chronic hepatitis C (CHC) infection is one of the most common chronic liver diseases worldwide[1] and is a major driver for liver cirrhosis, hepatocellular carcinoma (HCC)[2,3] and the need for liver transplantation.[4] Novel treatments for CHC with direct-acting antiviral (DAA) therapy result in high rates of sustained virological response (SVR) regardless of viral genotypes and patients' characteristics.[5] Previous studies have shown that SVR is associated with a reduced risk of hepatic de-compensation, need for liver transplantation and both liver-related and overall mortality.[6–9]

Liver steatosis (LS) is common in patients with CHC, and its presence is strongly associated with the metabolic syndrome,[10,11] with the exception of genotype 3 in which hepatic steatosis is related to viral load and low serum triglycerides levels but not to the metabolic syndrome.[12] In addition, LS is independently associated with progression to advanced fibrosis in patients with CHC, and both LS and advanced fibrosis are major risk factors for all-cause mortality and HCC in this population.[13]

The risk of HCC occurrence remains significant in CHC patients with advanced fibrosis even after treatment with DAAs,[14] and some reports even suggest an increased risk of de novo HCC following DAA treatment.[15] Although advanced liver fibrosis and cirrhosis were found to be important predictors of mortality and future development of HCC in this population, much less is known about the association of LS with these long-term outcomes in patients who eliminated HCV following DAA treatment.

In this study, we aimed to evaluate the incidence of mortality, development of HCC and extra-hepatic malignancies, de-compensation of liver disease and liver transplantation rates in patients who were treated for CHC with DAA-based regimens with or without LS at baseline. In addition, we assessed the individual effects of LS or advanced fibrosis on all-cause mortality and the development of HCC following DAA treatment.