Diabetes Mellitus, HCC Linked to Liver-Related Mortality in HCV Patients

Investigators have identified at least 2 new risk factors for liver-related mortality in patients with hepatitis C virus (HCV).

A team, led by Nobuhiro Hattori, Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, identified the risk factors linked to liver-related and non-liver-related mortality in patients with HCV following sustained virologic response to direct-acting antiviral agents.

The Study

In the retrospective, single-center cohort, the investigators examined 330 patients with HCV cured by DAAs. There was a median follow-up of 3.38 years. Each patient was administered IFN-free DAA treatment between September 2014 and January 2021 at the St. Marianna University Hospital. In addition, the patients with a history of hepatocellular carcinoma (HCC) did not have active HCC at the time of initiation of their final DAA therapy.

The study included 1481 person-years of follow-up, with 25 patients dying during the course of the study.

The investigators also collected data on age, sex, HCV genotype, history of HCC, previous DAA treatment, diabetes mellitus (DM), and hypertension history.

The team also collected laboratory test results, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, platelet, alpha-fetoprotein (AFP), and mac-2 binding protein glycan isomer (M2BPGi) before the final DAA treatment and at 12 weeks after the end of treatment.

Outcomes

The investigators sought primary outcomes of the incidence and predictors of liver-related and non-liver-related deaths of patients with HCV cured by IFN-free DAA treatment.

They also identified the cumulative all-cause, liver-related, and non-liver-related mortality using Kaplan-Meier methods and univariate and multivariate Cox proportional hazard models to identify the predictors of liver-related and non-liver-related deaths.

The results show a cumulative liver-related or non-liver-related mortality rate of 0.00 or 1.29% at year 1, compared to 2.87 or 3.60% at year 3 and 5.10 or 9.46% at year 5.

For liver-related deaths, 90% (n = 9) were from liver cancer, while the most common cause of non-liver-related deaths was malignancy.

After conducting a multivariate analysis using the Cox proportional hazard model, the investigators found diabetes mellitus (HR, 13.1; 95% CI, 2.81–61.3) and a history of hepatocellular carcinoma (HR, 12.8; 95% CI, 2.76–59.2), independently predicted liver-related death. There were no variables linked to non-liver-related death.

“Our findings suggest that DM and a history of HCC are risk factors for liver-related mortality of HCV patients cured by DAAs,” the authors wrote. “These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.”

The study, “Risk factors for liver-related mortality of patients with hepatitis C virus after sustained virologic response to direct-acting antiviral agents,” was published online in JGH Open.