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

Patients and Methods

Patients and Study Design

In this cross–sectional study, we included patients with pretreatment METAVIR F3 fibrosis or cirrhosis (F4), who had achieved SVR after HCV treatment at Karolinska University Hospital, Sweden, between 1992 and 2013. Patients with a liver transplantation or diagnosis of HCC prior to inclusion were excluded. We also excluded patients with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) coinfection.

Patients already followed up for HCC surveillance at the clinic were included in the study at their routine visits. However, many patients had been treated before HCC surveillance was an established practice or had been lost to follow–up for other reasons. These patients were identified from treatment records and were contacted and offered a follow–up visit and continued surveillance as appropriate according to current guidelines. Patients were included in the study between November 2008 and October 2016.

Sustained virological response was defined as a negative HCV RNA 6 months after the end of treatment, and follow–up time was calculated from this time–point. The pretreatment fibrosis stage was determined by the highest result of a pretreatment liver biopsy according to the METAVIR staging system or by a LSM with a median level of ≥9.5 kPa and ≥12.5 kPa corresponding to a METAVIR fibrosis stage of F3 and F4, respectively.[5,7] A clinical diagnosis of cirrhosis was also accepted. The date of the fibrosis stage defining measurement was considered the baseline date of the study, and we used baseline data on biochemistry, body mass index (BMI), alcohol abuse and diabetes mellitus from patient records within 6 months of this date.

At the clinical follow–up visit, we performed a liver stiffness measurement with FibroScan, calculated a BMI and tested for HCV RNA. A medical history was taken including questions on comorbidities and average alcohol consumption (grams per week over the last year). Only one clinical follow–up visit with LSM was included for each patient. For patients with multiple LSMs after achieved SVR, we included the most recent one.

The study was approved by the Regional Ethics Committee according to the guidelines of the Helsinki Declaration.

Measurement of Liver Stiffness

Liver stiffness was measured by transient elastography with FibroScan using the M and XL probes as appropriate. Only examinations with ten valid measurements, an interquartile range less than 30% of the median result and a success rate of at least 60% were included. The result was expressed as median LSM levels in kilopascals (kPa). As there are no established LSM cut–offs for post–SVR fibrosis stages, we used standard pretreatment cut–offs for corresponding METAVIR fibrosis stages: F0–1: <7 kPa, F2: 7.0–9.4 kPa, F3: 9.5–12.4 kPa and F4: >12.5 kPa.[5,7] Advanced fibrosis was defined as a median LSM level ≥ 9.5 kPa in this study.

Statistical Analysis

Continuous variables are presented as medians (range) and categorical variables as frequencies (percentages). The Mann–Whitney test was used for comparison of medians and the Fischer exact test for comparison of proportions. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) for persisting advanced fibrosis, defined as a liver stiffness value ≥ 9.5 kPa at follow–up. The risk factors included were gender, pretreatment fibrosis stage, age at SVR, alcohol consumption (grams per week), BMI and the presence of diabetes mellitus at follow–up.

The fibrosis stage at follow–up was correlated to follow–up time after SVR. We used the Kruskal–Wallis rank test for equality of populations. All tests were two–sided, and a P –value of <.05 was considered significant. Only complete data sets were analysed, and all statistical analyses were performed with Stata version 13.1 (StataCorp, TX, USA).