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

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.
Competing Interests: Financial disclosures: Florian Berger: noneLukas Buendgens: noneChristoph Boesecke: Speakers bureau: Abbvie, Gilead, Janssen, MSD, ViiV, Advisory board: Abbvie, Gilead, MSD, ViiVStefan Christensen: Speakers bureau: Abbvie, Gilead, Janssen; Advisory board: Abbvie, Gilead, Janssen, MSD, ViiVDietrich Hüppe: Speakers bureau: Abbvie, Gilead, Janssen, MSD; Advisory board: Abbvie, Gilead, Janssen.Patrick Ingiliz: Speakers bureau: Abbvie, Gilead, Janssen, MSD.Thomas Lutz: noneStefan Mauss: Speakers bureau: Abbvie, Gilead, Janssen; Advisory board: Abbvie, Janssen, MSD.Knud Schewe: Fees for consultancy and speaking from AbbVie, Bristol-Myers-Squibb, Gilead, Hexal, ViiV, Janssen, MSD.Karl Georg Simon: Speakers bureau: Abbvie, Gilead, Janssen; Advisory board: Abbvie, Janssen, MSD.Frank Tacke: Fees for consultancy and speaking from AbbVie, Bristol-Myers-Squibb, Gilead, Janssen, MSD. Financial support: none
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