Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct‐Acting Antivirals for Hepatitis C

Abstract

Sustained virologic response (SVR) after direct‐acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post‐SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR. Overall, 62% had improved liver stiffness that was consistent with regression of at least one stage of fibrosis. In the cirrhosis group, 48% showed fibrosis regression by at least two stages by TE (<9.5 kPa). In the F3 fibrosis group, 39% regressed by at least two stages (<7 kPa). The median time from SVR to regression by TE was 1 year. Fifteen patients with liver biopsies prior to SVR underwent a biopsy after SVR; 13 of these patients had improved liver stiffness (to <9.5 kPa). The post‐SVR liver biopsies of only 4 patients showed F1‐F2 while 11 patients showed F3‐F4; however, morphometry of the first 11 biopsied patients revealed that 10 patients had an average 46% decrease in collagen content. Conclusion: This is the first DAA study that also has paired liver biopsies showing fibrosis regression. After SVR is achieved, improvements in liver stiffness measured by TE are seen in a majority of patients with advanced fibrosis/cirrhosis within 2 years. TE improvements are overstated when compared to histologic staging but confirmed with morphometric analysis. It is unclear whether TE following SVR can reliably predict when patients no longer require advanced fibrosis/cirrhosis monitoring after SVR.

Transient elastography in DAA era. Relation between post‐SVR LSM and histology

“…In fact, in the Pan et al study, it was found that most of the patients whose LSM improved during followup still had advanced fibrosis or cirrhosis in liver biopsies. 4 TA B L E 1 ALT, FIB-4 and liver stiffness measurement (LSM) before and after sustained virological response (SVR) with liver histological results from ten patients they found substantial differences between both pre-and post-SVR…”

“…Changes in LSM may be due to a fast decrease in liver inflammation, but, in the long term, they might be explained by narrowing of fibrotic septa related to a reduction of collagen content, despite still having histological cirrhosis. In fact, in the Pan et al study, it was found that most of the patients whose LSM improved during follow‐up still had advanced fibrosis or cirrhosis in liver biopsies . However, they found substantial differences between both pre‐ and post‐SVR biopsies: (1) there was an improvement in liver inflammation in 73% of patients, and (2) there was improvement in sinusoidal fibrosis.…”

“…Recently, a study with serial LSM after SVR in patients with advanced fibrosis or cirrhosis showed that in 15 patients, in whom pre‐ and post‐SVR liver biopsies were available, LSM improved in most of them at least one stage of fibrosis, but 11 patients still had F3‐F4 in liver biopsy. Despite this, a marked reduction in collagen content was observed, thus demonstrating fibrosis regression . As adequate information regarding liver fibrosis staging post‐SVR is very important to decide long‐term follow‐up and hepatocellular carcinoma (HCC) screening policies, in the present study we aimed to assess the relation between liver histology and LSM after SVR with DAA in HCV patients.…”

“…Despite this, a marked reduction in collagen content was observed, thus demonstrating fibrosis regression. 4 As adequate information regarding liver fibrosis staging post-SVR is very important to decide long-term follow-up and hepatocellular carcinoma (HCC) screening policies, 5 in the present study we aimed to assess the relation between liver histology and LSM after SVR with DAA in HCV patients.…”

The Moral of Hepatic Fibrosis: Don’t Always Believe Noninvasive Fibrosis Measurements

“…Yet, fibrous bundles/septa bridging between portal tracts became thin, possibly suggesting regression of liver fibrosis. Pan et al [8] reported that among 15 patients with advanced fibrosis or cirrhosis (F3/F4) according to a pre-SVR liver biopsy who underwent a repeat biopsy post-SVR, only 4 patients showed improvement with F1-to-F2 fibrosis, whereas 11 patients still showed F3-to-F4 fibrosis. Nonetheless, morphometric analyses of the first 11 biopsied patients revealed that collagen content declined by an average of 46% over varying time intervals in 10 patients.…”