Metabolic Dysfunction Common in Patients Cured of Chronic Hepatitis C Virus

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Metabolic dysfunction was associated with increased risk of HCC, while patients with only metabolic dysfunction had the highest risk because the sustained virological response achievement.

Metabolic dysfunction is more common than ultrasonographic steatosis in patients cured of chronic hepatitis C virus (HCV) who were treated with direct-acting antivirals (DAA).1

A team, led by Serena Pelusi, Department of Transfusion Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, examined the impact of metabolic dysfunction in patients cured of chronic hepatitis C.

Metabolic Dysfunction

In the past, metabolic dysfunction-associated fatty liver disease is thought to identify individuals at risk of liver events regardless of the contemporary presence of other liver diseases.

“The metabolic dysfunction (MD)-associated fatty liver disease (MAFLD) concept has recently been proposed by an international multi-stakeholder consensus to replace non-alcoholic fatty liver disease (NAFLD) as the official definition for fatty liver disease associated with metabolic alterations and insulin resistance, the most prevalent chronic liver disorder worldwide,” the authors wrote. “Overall evidence suggests that the MAFLD definition can intercept better than NAFLD those individuals with more severe liver fibrosis and at risk of liver disease progression and HCC in the general population.”

The Cohort

In the study, the investigators analyzed data from a real-life cohort involving 2611 patients cured of CHC with DAA and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history in Italy.

The results show 58% of patients were affected by metabolic dysfunction, diagnosed primary because of the presence of diabetes (MD-diabetes, 19%), overweight without diabetes (MD-overweight, 37%) or multiple metabolic abnormalities without overweight, and diabetes (MD-metabolic, 2%).


Metabolic dysfunction was more frequent and not coincident with ultrasonographic steatosis (32% MD-only, 23% MD-US and 13% US-only). The dysfunction was also linked to higher liver stiffness (P <0.05), especially in patients with metabolic dysfunction-diabetes and metabolic dysfunction-only subgroups of older individuals with more advanced metabolic and liver disease (P <0.05).

After using Cox proportional hazard multivariable analysis, the team found metabolic dysfunction was associated with increased risk of HCC (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.27-3.04; P = 0.0023).

The investigators then used diagnostic criteria for further classification and found improved risk stratification (P <0.0001), with the highest risk found in patients with metabolic dysfunction-diabetes.

Patients with only metabolic dysfunction had the highest risk because the sustained virological response achievement (P = 0.008), with a later catch-up of those with combined metabolic dysfunction-ultrasonographic steatosis.

On the other hand, only ultrasonographic steatosis was not associated with HCC.

“By applying the [metabolic dysfunction] criteria in a real-life cohort of patients cured of CHC with advanced fibrosis, we found that [metabolic dysfunction] is more prevalent than [ultrasonographic steatosis] and identifies more accurately individuals with advanced liver disease at risk of developing de novo HCC,” the authors wrote. [Metabolic dysfunction] appears more useful than US to stratify the risk of HCC in patients cured of CHC with advanced fibrosis.”


Pelusi, S., Bianco, C., Colombo, M., Cologni, G., del Poggio, P., Pugliese, N., Prati, D., Pigozzi, M. G., D'Ambrosio, R., Lampertico, P., Fagiuoli, S., Valenti, L., Valenti, L., Pelusi, S., Prati, C. B., De Gasperi, E., D’Ambrosio, R., Lampertico, P., Aghemo, A., … Mendeni, M. (2023). Metabolic dysfunction outperforms ultrasonographic steatosis to stratify hepatocellular carcinoma risk in patients with advanced hepatitis C cured with direct‐acting antivirals. Liver International.