Letter to the Editor: Steatotic liver disease in chronic hepatitis C - a marker of systemic risk, not direct-acting antiviral treatment failure

Abstract

The study by Janczura et al, published in the recent issue of the World Journal of Hepatology, present real-world evidence on the clinical interplay between steatotic liver disease (SLD) and chronic hepatitis C in the era of direct-acting antivirals. Their findings revealed that SLD affects more than 40% of treated patients, characterizing a population marked by significant metabolic vulnerability, recurrently with older age, elevated body mass index, diabetes, and dyslipidemia. This positions SLD as a broader marker of systemic risk rather than an isolated hepatic condition. The strong association between SLD and genotype 3 further reinforces the lipotropic profile of this genotype. Although patients with SLD presented with more advanced fibrosis and experienced slightly lower sustained virologic response rates, the study clearly showed that SLD itself is not an independent predictor of direct-acting antivirals treatment failure. In contrast, cirrhosis and genotype 3 infections remain the main determinants of treatment failure. The high frequency of complications and mortality among individuals with SLD underscores the need for integrated metabolic, hepatic, and behavioral management, including alcohol risk mitigation. These insights highlight the importance of addressing SLD as a combined feature in chronic hepatitis C management, as it guides prognosis and the requirement for long-term metabolic monitoring, thereby optimizing outcomes in this population.

Key Words: Chronic hepatitis C; Direct-acting antiviral; Genotype 3; Liver cirrhosis; Steatotic liver disease; Liver fibrosis; Metabolic disfunction

Core Tip: This letter discusses the real-world findings of Janczura et al, who evaluated the impact of steatotic liver disease on chronic hepatitis C virus infection in the era of direct-acting antivirals. Their work highlights how metabolic dysfunction, aging, and genotype-specific characteristics contribute to persistent liver risk despite viral cure. By emphasizing the role of noninvasive steatosis assessment in identifying high-risk patients and guiding long-term monitoring, this correspondence reinforces the clinical relevance of steatotic liver disease in shaping the prognosis and follow-up strategies for individuals with current or past hepatitis C virus infection.

TO THE EDITOR

We are pleased to comment on the article by Janczura et al[1], published in the recent issue of the World Journal of Hepatology. In this real-world, observational study, the authors analyzed the interaction between steatotic liver disease (SLD) and chronic hepatitis C (CHC) virus infection in the era of direct-acting antivirals (DAAs)[1].

THE KEY FINDINGS

The authors reported that 42% of the evaluated patients presented with SLD, a prevalence higher than that expected for the general population in that region but consistent with data from individuals infected with HCV. Importantly, this subgroup exhibited significant metabolic vulnerability, including a higher body mass index, diabetes, and dyslipidemia, and the prevalence is even higher among individuals with metabolic risk factors: Up to 70%-80% of those with obesity or type 2 diabetes have SLD[2-4]. This alignment between the work and the global literature reinforces that the study did not suffer from a major population bias or overrepresentation of the disease burden.

A key finding of this study was that SLD itself is not an independent predictor of DAA treatment failure. However, cirrhosis and genotype 3 (GT3) infections remain the primary determinants of suboptimal response. Nonetheless, the observation that individuals with SLD experience more advanced liver disease, with higher rates of complications and mortality, emphasizes the necessity not only to treat hepatitis C but also to ensure rigorous metabolic, hepatic, and behavioral management, since the goal of therapy is to improve the survival and prognosis of these patients.

Another valuable insight after reading the article is the suggestion of adding non-invasive tools for grading SLD at the time of the diagnosis of CHC to map possible liver dysfunctions, stratify the risk of the patient, and guide an optimized multidisciplinary management, including not only DAAs, but also measures to reduce the metabolic vulnerability during CHC treatment. The American Association for the Study of Liver Diseases does not recommend performing non-invasive liver disease assessment for all patients with CHC; rather, they advise identifying cirrhosis or advanced fibrosis prior to antiviral therapy[5], which can be firmly discussed after the findings of the study.

The study also found that cirrhosis and GT3 infection were the only independent predictors of therapeutic failure in CHC, consistent with prior reports identifying both as major obstacles to achieving a sustained virologic response with DAA therapy[6,7]. Assessment of cirrhosis before initiating treatment is mandatory, as recommended by the American College of Physicians[8].

In contrast, routine hepatitis C virus genotyping is not required for all patients before starting pangenotypic DAA therapy, except when using glecaprevir-pibrentasvir, where GT3 infection necessitates a longer treatment duration[6,8]. Most patients with CHC are diagnosed and treated in non-tertiary centers, making universal genotyping logistically challenging and expensive.

Therefore, even considering the evidence of GT3 as a predictor of therapeutic failure, routine genotyping of all patients before DAA therapy is not necessary in the era of pangenotypic regimens, except in specific clinical scenarios[6,8]. This approach streamlines care, reduces costs, and maintains high efficacy in diverse patient populations.

CONCLUSION

After reading and commenting on this refined work, we express our respect for all contributing authors and participants of the study, which successfully highlighted an emerging global health problem: SLD in the CHC treatment scenario. Although SLD is not an independent determinant of DAA treatment failure, it clearly represents a systemic risk factor associated with more advanced liver disease and worse clinical outcomes. These findings reinforce the importance of comprehensive management strategies that extend beyond viral eradication, integrating metabolic risk assessment and multidisciplinary care to improve long-term prognosis in patients with CHC.