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Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response
Christoph Welsch1, Mira Efinger1, Michael von Wagner1
1Department of Internal Medicine 1, JW Goethe-University Hospital, Frankfurt/Main, Germany.
Insights
Even after successful Hepatitis C Virus (HCV) eradication, many patients experience ongoing liver inflammation. Key risk factors include male gender, advanced liver disease, and steatosis, highlighting the need for continued monitoring post-sustained virologic response (SVR).
Area of Science:
- Hepatology
- Virology
- Internal Medicine
Background:
- Direct-acting antiviral (DAA) therapies have significantly improved sustained virologic response (SVR) rates for chronic Hepatitis C Virus (HCV) infection.
- Despite viral eradication, persistent hepatic inflammation, indicated by elevated aminotransferase levels, can occur post-SVR.
- The prevalence and risk factors for this post-eradication inflammation require further investigation.
Purpose of the Study:
- To determine the prevalence of ongoing hepatic inflammation after achieving SVR in patients treated for chronic HCV.
- To identify baseline demographic and clinical factors associated with persistent aminotransferase elevation post-SVR.
- To compare inflammation rates between interferon (IFN)-based and DAA-based treatment regimens.
Main Methods:
- A post-hoc analysis of prospectively collected data from 834 patients who achieved SVR after HCV treatment.
- Patients were categorized based on treatment regimen: Pegylated Interferon (PegIFN)-based or DAA-based.
- Demographic, clinical data, and liver enzyme levels were analyzed to assess post-SVR inflammation and associated factors.
Main Results:
- A significant proportion of patients (up to 10% with ongoing elevation, 25% above healthy range) exhibited post-SVR aminotransferase elevation.
- Male gender, advanced liver disease, and markers of liver steatosis were independently associated with persistent ALT elevation.
- IFN-based antiviral treatment was correlated with higher post-SVR inflammation compared to DAA-based regimens.
Conclusions:
- This study reveals a high prevalence of ongoing hepatic inflammation in patients achieving SVR for HCV, even with modern DAA therapies.
- Identified risk factors such as male gender, advanced liver disease, and steatosis are crucial for predicting persistent inflammation.
- These findings have significant implications for managing approximately one-third of patients post-HCV eradication, suggesting a need for tailored follow-up strategies.
Background:
Novel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.
Methods:
This post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).
Results:
We observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.
Conclusion:
This is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.
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