Hepatic Steatosis in Chronic Hepatitis C

Hepatic steatosis, the intracellular accumulation of triglycerides within hepatocytes, is a frequent manifestation of chronic hepatitis C and affects up to 80 percent of infected individuals. Its pathogenesis involves both direct viral effects—particularly by genotype 3, which modulates lipid-processing pathways—and host metabolic factors such as insulin resistance, obesity and dyslipidaemia. Steatosis contributes to accelerated fibrosis progression, increased risk of cirrhosis and hepatocellular carcinoma, and may undermine antiviral treatment efficacy. Although direct-acting antivirals (DAAs) achieve high rates of viral eradication, the trajectory of steatosis following sustained virological response (SVR) is heterogeneous: some patients experience improvement of fat deposition, while others develop or sustain liver fat accumulation driven by metabolic derangements. Given the global burden of hepatitis C, understanding and monitoring steatosis remain crucial for optimising long-term liver health and preventing extrahepatic complications.

Research from Nature Portfolio

Recent studies have employed non-invasive and molecular methods to characterise steatosis dynamics after antiviral cure. One investigation using controlled attenuation parameter (CAP) elastography reported a significant but modest decline in liver fat content after DAA-induced SVR, alongside rises in both low-density and high-density lipoprotein cholesterol, suggesting reversal of viral lipid sequestration. A transcriptome-wide comparison of genotype 1 and 3 infections revealed genotype-dependent shifts in lipid turnover and inflammatory gene networks, indicating that genotype 1 drives greater lipogenic and lipolytic activity but lower inflammatory signalling. A paired liver biopsy study demonstrated that most patients exhibit reductions in steatosis and overall inflammatory activity post-SVR; however, a subset retained portal lymphocytic inflammation and isolated cases of steatosis rebound correlated with adverse clinical outcomes. Taken together, these findings underscore the multifaceted nature of steatosis resolution and persistence after hepatitis C eradication.

Hepatic Steatosis in Chronic Hepatitis C publication trend

The graph below shows the total number of articles in hepatic steatosis in chronic hepatitis c across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatic steatosis: Intracellular accumulation of triglycerides within liver cells.

Direct-acting antivirals (DAAs): Agents targeting specific hepatitis C viral proteins to achieve viral eradication.

Controlled attenuation parameter (CAP): A quantitative ultrasound measure of hepatic fat content obtained during elastography.

Fibrosis-4 (FIB-4) score: A composite index using age, liver enzymes and platelet count to estimate hepatic fibrosis.

PNPLA3 variant: A genetic polymorphism in the patatin-like phospholipase domain containing 3 gene linked to fatty liver susceptibility.

References

1. Weight Gain and Increased Body Mass Index in Patients with Hepatitis C after Eradication Using Direct-Acting Antiviral Therapy in Taiwan. Diagnostics (2024).
2. Eradication of hepatitis C virus is associated with the attenuation of steatosis as evaluated using a controlled attenuation parameter. Scientific Reports (2018).
3. Steatosis and hepatitis C. Gastroenterology Report (2015).
4. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines (2021).
5. Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response. Diagnostics (2022).
6. Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver. Scientific Reports (2019).
7. Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome. Scientific Reports (2021).
8. Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants. PLOS ONE (2022).