Cirrhosis, High Age and High Body Mass Index Are Risk Factors for Persisting Advanced Fibrosis After Sustained Virological Response in Chronic Hepatitis C

M. Hedenstierna; A. Nangarhari; A. El-Sabini; O. Weiland; S. Aleman


J Viral Hepat. 2018;25(7):802-810. 

In This Article

Abstract and Introduction


We aimed to assess fibrosis with liver stiffness measurement long–term after sustained virological response of chronic hepatitis C and to identify risk factors associated with persisting fibrosis. In this cross–sectional study, patients with chronic hepatitis C and pretreatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon–containing regimen underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow–up time of 7.7 years (range 0–20), 84 with a follow–up time of ≥10 years. Patients with pretreatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7–9.1) at follow–up, than patients with advanced fibrosis (6 kPa 95% CI 5.5–6.4). A majority improved their fibrosis stage after sustained virological response, but 24% had persisting advanced fibrosis with a liver stiffness level of ≥ 9.5 kPa. Among patients with pretreatment cirrhosis, the proportion with persisting advanced fibrosis diminished with longer follow–up time, from 48% after <5 years to 21% after >10 years. The main risk factors for persisting advanced fibrosis were pretreatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long–term follow–up after sustained virological response in hepatitis C patients with pretreatment advanced liver fibrosis. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virological cure.


Infection with hepatitis C virus (HCV) is a global health problem with an estimated 70 million chronically infected people and 750 000 deaths every year from HCV–related causes.[1,2] The risk for HCV–related morbidity and mortality increases with the stage of liver fibrosis, and patients with compensated cirrhosis have an annual risk of 7% to develop decompensated liver disease or hepatocellular carcinoma (HCC).[3] Current guidelines therefore recommend surveillance for HCC with ultrasound every 6 months for patients with HCV–related advanced liver fibrosis or cirrhosis.[4] Because of this, accurate measurement of hepatic fibrosis is important for the clinical management of patients with chronic HCV infection.

The gold standard for staging liver fibrosis is by liver biopsy. A liver biopsy provides information on the stage of liver fibrosis, but also on the necroinflammatory activity in the liver.[5] In recent years, liver stiffness measurement (LSM) by transient elastography has replaced liver biopsy in clinical practice in many countries. This noninvasive method measures the liver stiffness by ultrasound and yields a composite result of both liver fibrosis and inflammation.[6] LSM is accurate for the diagnosis of significant fibrosis and cirrhosis in patients with chronic hepatitis C and correlates to the degree of portal hypertension and the risk to develop HCC.[7–9] LSM is less validated in patients with sustained virological response (SVR) after HCV treatment, and there are no established LSM cut–offs for fibrosis stages after achieved SVR.[10] The risk to develop HCC and other liver–related complications decreases after SVR, but does not disappear.[4,11,12] Pretreatment cirrhosis and persisting cirrhosis after achieved SVR has been associated with a high post–treatment risk for liver–related complications and HCC.[13–16] Recent studies have investigated the association of LSM levels at SVR with the risk to develop HCC, but with contradicting results.[17,18]

Several studies with paired liver biopsies have shown that liver fibrosis and cirrhosis will improve after achieved SVR in a majority of patients, but also that, in 1%–14% of patients, fibrosis will progress.[19–21] Most studies on fibrosis regression after SVR have short follow–up times, and the long–term effect of achieved SVR on liver fibrosis is less well studied. We also lack knowledge on the long–term effect of comorbidities and other risk factors on liver fibrosis after achieved SVR.

The aim of this study was to investigate the long–term effect of achieved SVR on liver fibrosis, measured as liver stiffness with transient elastography, in a cohort with pretreatment advanced chronic HCV infection. We also aimed to identify risk factors associated with persisting fibrosis.