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Daily Dose: Impact of Metabolic Dysfunction in Persons Cured of Chronic HCV


Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On April 12, 2023, we reported on a study published in the journal Liver International that examined the clinical implications of using the metabolic dysfunction (MD)-associated fatty liver disease (MAFLD) definition to predict major clinical events (hepatic cellular carcinoma [HCC] and cardiovascular events [CVE]) in patients with advanced liver fibrosis after eradication of hepatis C virus (HCV).

The study

For the study, investigators took advantage of the NAVIGATORE-Lombardia study database, a population-based real-world cohort created to study the impact of metabolic comorbidities on HCC and CVE after antiviral treatment. They selected an initial 8740 participants with information available on age, sex, anthropometric features, fibrosis staging, metabolic co-morbidities, and pharmacologic history.

After exclusions, the final cohort numbered 2611 participants cured of chronic HCV who had advanced liver fibrosis, did not have HBV or HIV, had no history of liver transplantation, and were negative for HCC. Median age of the cohort was 61.4 years and 63.9% were men. males, median follow-up 34 months.

Participants were followed (median duration 34 months) for HCC and CVE, defined as hospitalization due to ischemic heart disease or heart failure and sudden death.

The findings

Investigators found that 58% of patients had MD, 19% based on the presence of diabetes (MD-diabetes), 37% based on increased adiposity without diabetes (MD-overweight), and just 2% based on multiple metabolic abnormalities without overweight or diabetes (MD-metabolic).

MD was more prevalent than US (32% MD-only, 13% US-only) and MD-US diagnoses were coincident in less than one-quarter of participants (23% MD-US), suggesting that MAFLD prevalence, not requiring confirmation of US to accompany a positive history, may be higher than previously expected.

Liver stiffness was more pronounced in participants with MD (P<.05), particularly in those subgroups with MD-diabetes and MD-only whose members were older and had more advanced MD and liver disease (P<.05). Using multivariable Cox proportional hazard regression to evaluate independent predictors of clinical events, investigators reported that MD was associated with an approximately 2-fold higher risk of developing de novo HCC (hazard ratio [HR], 1.97, 95% CI, 1.27-3.04; P=.0023).

Additional classification according to MD diagnostic criteria improved risk stratification (P<.001), the authors reported, with the highest risk, by approximately 3-fold, observed in patients with MD-diabetes, (HR, 3.03, 95% CI 1.86– 4.95; P<.001) followed by those with MD-only ( HR 1.92, 95%CI 1.20-3.07; P=.0064).

Patients with MD-only appeared at highest risk of HCC after achieving sustained virologic response (P=.008), with catch up in risk later for those with MD-US. The researchers found no association between having US-only and HCC.

Note from authors

"By applying the MD criteria in a real-life cohort of patients cured of CHC with advanced fibrosis, we found that MD is more prevalent than US and identifies more accurately individuals with advanced liver disease at risk of developing de novo HCC. MD appears more useful than US to stratify the risk of HCC in patients cured of CHC with advanced fibrosis."

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