MASLD, Metabolic Risk Factors Linked to Fibrosis Progression in HCV

Giada Sebastiani, MD

Credit: McGill University

Metabolic dysfunction–associated steatotic liver disease (MASLD) is associated with significant liver fibrosis in individuals with a history of hepatitis C virus (HCV) infection, according to findings from a recent study.¹

Results underscore the importance of a comprehensive approach to managing patients with HCV, including the early identification and management of metabolic risk factors and personalized care due to the differential impact of MASLD phenotypes.¹

According to the World Health Organization, globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring each year. Although the introduction of direct-acting antivirals has facilitated cure rates exceeding 95%, HCV remains a leading cause of liver cirrhosis and hepatocellular carcinoma, and concerns about metabolic complications associated with HCV persist, both during infection and post-cure.^1,2

“The co-occurrence of MASLD and HCV-related metabolic complications, whether during chronic HCV infection or post-SVR, may contribute to a synergistic effect, exacerbating liver injury through steatosis, oxidative stress and cellular dysfunction,” Giada Sebastiani, MD, an associate professor of medicine at McGill University and a clinician scientist at the Research Institute of McGill University Health Centre, and colleagues wrote.¹ “It remains uncertain whether steatosis alone is responsible for this effect or if other factors are involved.”

To assess the association between MASLD and HCV with liver fibrosis, investigators conducted a retrospective cross-sectional study of consecutive adult patients with a history of chronic HCV infection who underwent transient elastography with controlled attenuation parameter (CAP) between October 2015 and December 2023 at McGill University Health Center and the Ottawa Hospital.¹

MASLD was identified based on the presence of steatosis, defined as CAP ≥ 275 dB/m, and ≥ 1 cardiometabolic risk factor:

• Overweight MASLD: BMI ≥ 25 kg/m2
• Hypertensive MASLD: blood pressure ≥ 130/85 mmHg or on antihypertensive medication
• Diabetic MASLD: prediabetes, defined as fasting glucose levels 5.6–6.9 mmol/L, 2-h post-load glucose levels 7.8–11.0 mmol/L, or an HbA1c 5.7%–6.4%; or type 2 diabetes, defined as fasting glucose levels > 6.9 mmol/L, 2-h post-load glucose levels > 11.0 mmol/L, or HbA1c > 6.4%; or receiving diabetes treatment
• Dyslipidemic MASLD: triglycerides ≥ 1.70 mmol/L or HDL cholesterol < 1.0 mmol/L for men and < 1.3 mmol/L for women, or on lipid-lowering treatment

The study’s primary outcome was the association between MASLD and its phenotypes with significant liver fibrosis in individuals with a history of HCV infection. Additionally, investigators compared the prevalence of significant liver fibrosis in MASLD patients to those without steatosis and those with steatotic liver disease (SLD) without cardiometabolic conditions.¹

In total, the study included 590 patients with a median age of 53 years who were predominantly male (61%) and White (76%). Among the cohort, the mean duration of HCV infection was 10 years, and 74% of the study population achieved SVR.¹

Significant liver fibrosis, defined as liver stiffness measurement (LSM) > 7.1 kPa, was present in 45% of the cohort, and 36% had SLD. Of those with SLD, 31% met the criteria for MASLD and 5% were classified as having HCV-related steatosis.¹

Investigators noted the most frequent phenotypes were the intersection of overweight and hypertensive MASLD and hypertensive MASLD alone, both accounting for 30% of MASLD cases.¹

The prevalence of significant liver fibrosis was the greatest among people with MASLD (58%) followed by HCV-related steatosis (45%) and the non-steatosis group (39%). After adjusting for potential confounders, MASLD was associated with significant liver fibrosis (adjusted odds ratio [aOR], 2.29; 95% confidence interval [CI], 1.07–4.87).¹

Further analysis of specific MASLD phenotypes revealed diabetic MASLD (odds ratio [OR], 4.76; 95% CI, 2.16–10.49), overweight MASLD (OR, 2.54; 95% CI, 1.27–5.07), and hypertensive MASLD (OR, 3.44; 95% CI, 1.77–6.68) were significantly associated with fibrosis.¹

“Our findings underscore the importance of a comprehensive approach to managing patients with HCV, even after viral eradication,” investigators concluded.¹ “Early identification and management of metabolic risk factors, especially diabetes and hypertension, could potentially reduce the risk of fibrosis progression, improving long-term outcomes. Furthermore, the differential impact of MASLD phenotypes highlights the need for personalized care, where interventions are tailored based on individual risk profiles to prevent or slow the progression of liver disease.”

References

1. ^{Elgretli W, Shengir M, Sasson S, et al. Association of MASLD Phenotypes With Liver Fibrosis in Hepatitis C: The Role of Cardiometabolic Risk Factors. Journal of Viral Hepatitis. https://doi.org/10.1111/jvh.70004}
2. ^{World Health Organization. Hepatitis C. April 9, 2024. Accessed January 28, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}