Risk factors for remaining liver injury in patients with virological elimination of chronic hepatitis C

Abstract

Background and aims Disease activity, but also demographics, lifestyle, and comorbidities, may influence alanine aminotransferase (ALT) levels in hepatitis C virus (HCV)-infected patients. Direct-acting antiviral agents (DAA) achieve virological cure in > 90 % of patients, regardless of HCV genotype and fibrosis stage. This allows assessing determinants for ALT levels before and after elimination of HCV. Methods Our prospective cohort included HCV- and HIV/HCV-infected patients treated with DAA at 9 German centers (GECCO cohort). We analyzed all consecutive patients with sustained virological response (SVR) at week 12 (SVR12) and/or 24. Normal ALT was defined as ≤ 35 U/L, regardless of sex. Results At baseline, 1477 out of 1774 patients (83 %) had ALT > 35 U/L, and 297 (17 %) had ALT ≤ 35 U/L. Baseline ALT > 35 U/L was independently associated with male sex, higher body mass index (BMI), liver cirrhosis, and not being on opioid substitution. After SVR, > 80 % of patients normalized ALT, and even patients with low baseline ALT further reduced ALT levels. However, ALT remained > 35 U/L in 15 % (221/1477) after SVR12. By multivariate analysis, ALT > 35 U/L at SVR12 was associated with male sex, higher BMI, liver cirrhosis, baseline ALT, HCV genotype 2, and younger age. Obesity, cirrhosis, and ALT were also independent factors associated with ALT > 15 U/L at SVR12 in patients with normal ALT at baseline. Conclusions Male sex, advanced liver fibrosis, and obesity are main risk factors for the lack of ALT normalization and/or ALT decline after SVR, indicative of fatty liver disease as a relevant comorbidity in hepatitis C.

Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C patients treated with DAAs

“…Our findings align well with smaller cohort studies from Spain (n = 1112) and Germany (n = 834), in which 11.7% or 10% had persistently elevated ALT . We had previously reported up to 15% with elevated ALT (221/1477) after DAA therapy from a different outpatient cohort of HCV‐infected patients . If the stricter AASLD criteria for normal ALT are applied, 38.5% of the patients in our current study (1906/4946) had persistently abnormal ALT despite DAA therapy.…”

“…7,8 We had previously reported up to 15% with elevated ALT (221/1477) after DAA therapy from a different outpatient cohort of HCV-infected patients. 9 If the stricter AASLD criteria for 8 Our study confirms and extends these findings, by pointing towards obesity/NAFLD, alcoholism and cirrhosis as the main relevant co-factors in HCV-infected patients. However, we need to acknowledge that steatosis was assessed by ultrasound in our registry, as done in similar prior studies with IFN-based therapies, 16 but not by controlled attenuation parameter (CAP), magnetic resonance spectroscopy (MRS), MRI-Proton density fat fraction (MRI-PDFF) or histology, which would have been more accurate and more quantitative to assess steatosis.…”

“…More recently, fatty liver, due to metabolic syndrome or excessive alcohol consumption, has gained attention as a considerable and enduring comorbidity after SVR with DAA . We and others have hypothesized that persistently altered liver tests after SVR may be suitable to indicate such relevant hepatological conditions in HCV‐infected patients treated with DAA . In this study, we explored this hypothesis in a large, prospectively enrolled nation‐wide registry cohort.…”

“…6 We and others have hypothesized that persistently altered liver tests after SVR may be suitable to indicate such relevant hepatological conditions in HCV-infected patients treated with DAA. [7][8][9] In this study, we explored this hypothesis in a large, prospectively enrolled nationwide registry cohort. Based on 4946 patients treated for hepatitis C in the German Hepatitis C-Registry, we analysed risk factors for elevated biochemical markers of liver disease (ALT, GGT) before and after DAA treatment of hepatitis C. The aim was to define risk factors for biochemical liver injury and the effect of the resolution of hepatitis C infection on the pattern of risk factors.…”

Postsustained Virological Response Management in Hepatitis C Patients

“…Noureddin et al 51 found that 47.5% of the patients who achieved an SVR had NAFLD, with some patients, having clinically significant fibrosis despite presenting with normal liver enzymes. In a recent study from Mauss et al, 52 male sex, advanced liver disease, and obesity were associated with persistence of ALT elevations in patients with SVR, suggesting fatty liver disease could be a potential cofactor of fibrosis progression. These authors therefore recommend to search for steatosis after SVR and continue lifelong surveillance in patients with documented fatty liver disease.…”