Advanced hepatic fibrosis and steatosis are associated with persistent alanine aminotransferase elevation in chronic hepatitis C patients negative for hepatitis C virus RNA during pegylated interferon plus ribavirin therapy.
BACKGROUND
Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin (peg-IFN/RBV) therapy remain unknown.


METHODS
A total of 1113 CHC patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled. Baseline characteristics associated with persistent on-treatment ALT elevation (POAE), and its impact on treatment outcomes, were investigated.


RESULTS
Of 1113 CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1) who had complete early virologic response (EVR) and received 48 weeks of therapy, patients with POAE had a lower rate of sustained virologic response (SVR) than those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that body mass index ≥ 27 kg/m(2), ALT level ≥3 times the upper limit of normal, aspartate aminotransferase to platelet ratio index score ≥1.5, hepatic fibrosis ≥F3, and hepatic steatosis ≥S2 were independent factors associated with POAE after viral clearance.


CONCLUSIONS
POAE is common in CHC patients during therapy. HCV-1 patients with POAE have a lower SVR rate to 48-week therapy if they achieve complete EVR. Advanced hepatic fibrosis, obesity, and steatosis are factors associated with POAE in these patients.
Department of Internal Medicine, Far Eastern Memorial Hospital Oriental Institute of Technology.
Cheng-Chao
CC
Liang
Department of Internal Medicine Hepatitis Research Center, National Taiwan University Hospital Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine.
Chen-Hua
CH
Liu
Department of Internal Medicine, Far Eastern Memorial Hospital.
Chen-Shuan
CS
Chung
Department of Internal Medicine, Far Eastern Memorial Hospital.
Cheng-Kuan
CK
Lin
Department of Internal Medicine Hepatitis Research Center, National Taiwan University Hospital Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine.
Tung-Hung
TH
Su
Hepatitis Research Center, National Taiwan University Hospital Department of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital.
Hung-Chih
HC
Yang
Department of Internal Medicine Hepatitis Research Center, National Taiwan University Hospital Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine.
Chun-Jen
CJ
Liu
Department of Internal Medicine Hepatitis Research Center, National Taiwan University Hospital Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine.
Pei-Jer
PJ
Chen
Department of Internal Medicine Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Ding-Shinn
DS
Chen
Department of Internal Medicine Hepatitis Research Center, National Taiwan University Hospital Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine.
Jia-Horng
JH
Kao
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood* / Q000378:metabolism; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000201:enzymology / Q000473:pathology*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000473:pathology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000302:isolation & purification*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
HCV RNA; alanine aminotransferase; chronic hepatitis C; hepatic fibrosis; steatosis