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.

Zusammenfassung

Einleitung Alanin-Aminotransferase (ALT)-Spiegel bei Hepatitis-C-Virus (HCV) infizierten Patienten werden durch die Krankheitsaktivität der Hepatitis C, aber auch durch Demografie, Lebensstil und Komorbiditäten beeinflusst. Direkt wirkende antivirale Agenzien (DAA) erzielen eine virologische Ausheilung in > 90 % der Patienten, unabhängig von HCV-Genotyp und Fibrose-Stadium. Dies ermöglicht festzustellen, welche Faktoren ALT-Spiegel vor und nach der Eliminierung von HCV determinieren.

Methode Die GECCO-Kohorte ist eine prospektive Kohorte aus HCV- und HIV/HCV-infizierten Patienten, die in neun deutschen Zentren mit DAA behandelt wurden. Wir analysierten alle konsekutiven Patienten mit anhaltender virologischer Remission (SVR) in Woche 12 (SVR12) und/oder 24. Eine normale ALT wurde definiert als ≤ 35 U/L, unabhängig vom Geschlecht.

Ergebnisse Zu Studienbeginn hatten 1477 von 1774 Patienten (83 %) eine ALT > 35 U/L, und 297 (17 %) zeigten eine ALT ≤ 35 U/L. Baseline ALT > 35 U/L war unabhängig mit männlichem Geschlecht, höherem Body-Mass-Index (BMI), Leberzirrhose und fehlender Opiat-Substitution assoziiert. Nach der SVR normalisierten > 80 % der Patienten die ALT, und sogar Patienten mit niedriger Baseline-ALT senkten die ALT-Werte weiter. ALT blieb jedoch nach SVR12 bei 15 % (221/1477) bei > 35 U/L. In einer multivariaten Analyse war ALT > 35 U/L nach SVR12 mit männlichem Geschlecht, höherem BMI, Leberzirrhose, Ausgangs-ALT, HCV-Genotyp 2 und jüngerem Alter assoziiert. Adipositas, Zirrhose und ALT waren bei Patienten mit normaler ALT zu Studienbeginn ebenfalls unabhängige Faktoren, die mit ALT > 15 U/L bei SVR12 assoziiert waren.

Diskussion Männliches Geschlecht, fortgeschrittene Leberfibrose und Adipositas sind Hauptrisikofaktoren für das Fehlen von ALT Normalisierung und/oder ALT Rückgang nach SVR, was auf eine Fettleber als relevante Komorbidität bei Hepatitis C hinweist.

Key words

HCV - NAFLD - real-life cohort - cirrhosis - SVR12 - ALT

Schlüsselwörter

HCV - NAFLD - Real-Life-Kohorte - Zirrhose - SVR12 - ALT

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