Severe fibrosis improves in most people after hepatitis C cure but persists in a quarter

Hepatitis C virus (HCV)-related liver fibrosis improves significantly in the majority of people with pre-treatment advanced fibrosis or cirrhosis after treatment resulting in a sustained virological response, Swedish investigators report in the Journal of Viral Hepatitis.

However, advanced fibrosis persisted in a quarter of people and worsened in a small subset of people, showing the need for regular monitoring after successful HCV therapy. Pre-treatment cirrhosis, older age and high body mass index were risk factors for the persistence of advanced cirrhosis.

“Our study shows that the vast majority of our 269 patients with pre-treatment advanced fibrosis or cirrhosis improved their fibrosis during long-term follow-up after SVR [sustained virological response],” comment the researchers. “A minority, however, continued to have advanced fibrosis even after more than 5-10 years follow-up. In this subset of patients, a point of no return for advanced liver fibrosis might have been reached, where improvement is not possible.”

The risk of serious illness and death caused by HCV is related to fibrosis stage. Accurate monitoring of fibrosis stage is therefore essential for the treatment of people with HCV.

Safe and effective treatment is now available for HCV. The aim of this treatment is a sustained virological response (SVR) – undetectable HCV RNA six months after the completion of therapy.

Investigators in Sweden wanted to examine the long-term effect of SVR on liver fibrosis among people with advanced fibrosis before the initiation of HCV therapy. They also aimed to determine the risk factors associated with the persistence of advanced fibrosis.

They therefore designed a cross-sectional study involving people with chronic HCV infection who attained SVR after therapy. All had advanced fibrosis (F3) or cirrhosis (F4) before the initiation of therapy. Individuals with liver cancer were ineligible for inclusion, and analysis was restricted to people with HCV mono-infection.

Post-SVR fibrosis stage was measured using FibroScan, an assessment of liver stiffness. A liver stiffness of 9.5 kPa is indicative of advanced fibrosis and 12.5 kPa or above shows the presence of cirrhosis.

Demographic information and medical history were obtained from the patients’ medical records. All the participants received now obsolete interferon-based treatment.

Pre-treatment fibrosis stage was determined by liver biopsy in 181 people, by liver stiffness measurement in 81 individuals and by a clinical diagnosis of cirrhosis in seven people. Overall, 44% of participants had pre-treatment cirrhosis and 59% were male. Median age at SVR was 53 years.

The median duration of follow-up was 7.7 years. But this varied considerably. Follow-up time was below five years for 115 people, between five and ten years for 70 individuals and was over ten years for 84 individuals.

Median body mass index (BMI) at follow-up was 26 kg/m² and 17% were obese (BMI over 30 kg/m²). Diabetes was diagnosed in 13% of people, with approximately a fifth developing diabetes after SVR.

Median liver stiffness at baseline was 13.9kPa but fell to 6.6 kPa during follow-up. Individuals with pre-treatment cirrhosis had significantly higher liver stiffness post-SVR (median 8.5 kPa) compared to those with advanced fibrosis (median 6 kPa).

The majority (87%) of people with advanced fibrosis pre-treatment experienced an improvement in liver stiffness after SVR. Similarly, liver stiffness improved after SVR in 83% of individuals with pre-treatment cirrhosis. Liver stiffness appeared to diminish over time in those with pre-treatment cirrhosis; whereas 48% of those with less than five years of follow-up still had a liver stiffness measurement above 9.5 kPA, only one-fifth (21%) of those followed for ten years or more still had a liver stiffness measurement above this level.

However, fibrosis stage did not improve in 17% of those with pre-treatment advanced fibrosis. Nor was there an improvement in 13% of people with pre-therapy cirrhosis. Moreover, in 5% of people, fibrosis stage worsened post-SVR.

Overall, 64 people (24%) had mean liver stiffness levels of at least 9.5 kPa after SVR, indicating the persistence of advanced fibrosis. Approximately three-quarters of these people had baseline cirrhosis.

Persistence of advanced fibrosis after SVR was associated with pre-treatment cirrhosis (OR = 3.9; 95% CI, 2.0-7.2), age 55 years and older (OR = 2.3; 95% CI, 1.2-4.3) and a BMI above 25 kg/m² (OR = 2.3; 95% CI, 1.1-4.6).

People who are overweight should be supported to lose weight before starting HCV therapy, suggest the authors.

Seven people with baseline advanced fibrosis progressed to cirrhosis after SVR. These people were more likely to have diabetes than those who did not progress to cirrhosis (p = 0.02).

“Although this study was not designed to assess the correlation between LSM [liver stiffness measurement] and the risk to develop HCC [hepatocellular carcinoma], there were patients in our study who improved fibrosis who later developed HCC up to 15 years after SVR,” note the authors. “This finding supports that surveillance for HCC should continue even in patients where cirrhosis has regressed after achieved SVR.”

They conclude, “liver fibrosis after achievement of SVR improved in the vast majority of our patients after long-term follow-up. Our data indicates that fibrosis regression is an on-going long-term process over years.”