Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection

Abstract

BACKGROUND & AIMS Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. METHODS We collected data from participants in the Chronic Hepatitis Cohort Study—a large observational multicenter study of patients with hepatitis at 4 US health systems—from January 1, 2006, through December 31, 2013. We calculated patients’ FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. RESULTS In propensity score–adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. CONCLUSIONS SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

“…Similarly, more than 80% of patients with persistently high FIB‐4/APRI scores had a diagnosis of cirrhosis, providing support to the validity of cirrhosis definition. Few patients with a cirrhosis diagnosis had persistently low FIB‐4/APRI score—an observation that was not entirely unexpected given the relatively low sensitivity of most noninvasive markers in identifying advanced fibrosis (including FIB‐4 and APRI at the cutoffs used for this study) . We explored the possibility that this subgroup might have been misclassified as cirrhosis; however, we did not find any significant differences in the distribution of cirrhosis diagnoses codes (number of instances, types) between cirrhosis patients with low versus high FIB‐4/APRI.…”

Management of the patient with SVR

“…However, patients who continued to exhibit F3 or F4 fibrosis are still at risk for developing HCC [55,38,56]. A meta-analysis by Messori et al, which included 25 studies from different parts of the world, showed a risk reduction of 6.7% (95% CI: 5-8) in non-cirrhotic patients vs. 22% (95% CI: [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] in patients with cirrhosis [57]. Accordingly, patients with advanced fibrosis and cirrhosis should continue to undergo surveillance for HCC every six months using ultrasonography with or without alpha-fetoprotein [38,52].…”

“…For the patient with SVR in whom resolution of the inflammatory component is expected, the specific thresholds to define the remaining fibrosis are likely to be different than pre-SVR. Fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) levels sharply decline after SVR and remain low compared to untreated patients [23]. Indeed, serologic tests alone appear to have suboptimal performance characteristics in predicting severity of fibrosis among those with SVR [24].…”

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk

“…Studies from the IFN-era showed that while HCC risk was reduced with SVR, the incidence of HCC was constant for at least 5 years afterwards (21, 48). On the other hand, studies with long term follow-up in the IFN-era also demonstrate that SVR is associated with durable improvements in laboratory markers of liver disease severity including platelet count and albumin (48) as well as FIB-4 and APRI scores (49). Improvements in these laboratory parameters as well as fibroscan-derived liver stiffness may correlate with reductions in HCC risk, although evidence to support this is still needed.…”