September 10, 2013

Clinical Presentation, Outcome, and Response to Therapy Among Patients With Acute Exacerbation of Chronic Hepatitis C

Clinical Gastroenterology and Hepatology
Volume 11, Issue 9 , Pages 1174-1180.e11, September 2013

Evangelista Sagnelli, Mariantonietta Pisaturo, Maria Stanzione, Vincenzo Messina, Loredana Alessio, Caterina Sagnelli, Mario Starace, Giuseppe Pasquale, Nicola Coppola

published online 15 April 2013.


Background & Aims

The slow asymptomatic progression of chronic hepatitis C (CHC) can be interrupted by an acute exacerbation, characterized by increased serum levels of alanine aminotransferase (ALT) and bilirubin and other symptoms of acute hepatitis. We aimed to provide more information about the clinical presentation of acute exacerbation of CHC.


We identified 82 consecutive patients, from 2 locations in Italy, who had an acute exacerbation of CHC from January 2005 through June 2010; we followed them up for a median period of 36 months. These cases were hepatitis C virus (HCV) RNA positive, hepatitis B surface antigen-negative, and had not received anti-HCV therapy. They were matched with 82 subjects with hepatitis C without reactivation for age, sex, and HCV genotype (controls). Sixty-nine cases and 73 controls were followed up for at least 2 years. Liver biopsy specimens had been taken from 23 cases and 31 controls—once before enrollment in the study and once during the follow-up period.


HCV genotype 2 was detected in 46.4% of cases, and HCV genotype 1 was detected in 43.9%. Among cases, the mean ALT level was 1063 ± 1038 IU/dL, and the mean total bilirubin level was 15.87 ± 7.15 mg/dL. A higher percentage of cases carried the interleukin-28B CC genotype than controls (40.2% vs 24.4%; P < .05). Among cases, 43.5% had a steady increase in ALT level (>2-fold baseline value); for 56.5% of these patients, ALT levels returned to baseline values before the acute exacerbation of chronic hepatitis. Based on comparisons of biopsy specimens, 18 cases (78.3%) and 11 controls (35.5%) had increasing fibrosis, with Ishak scores increasing by more than 2 (P < .005); 14 cases (60.9%) and 3 controls (9.6%) had increases in necroinflammation of more than 2 points (P < .005). Thirty-two cases (46.4%) and 38 controls (52%) received treatment with pegylated interferon and ribavirin; a sustained virologic response was achieved in 26 cases (81.2%) and 23 controls (60.5%).


Although an acute exacerbation of chronic hepatitis is a serious medical condition, most patients achieve a sustained virologic response after treatment with pegylated interferon and ribavirin.

Keywords: Hepatic Flare , Cirrhosis , Response to Therapy , Complication

Abbreviations used in this paper: ALT, alanine aminotransferase, AST, aspartate aminotransferase, CHC, chronic hepatitis C, HAI, Histologic Activity Index, HAV, hepatitis A virus, HBsAg, hepatitis B surface antigen, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, HDV, hepatitis D virus, HEV, hepatitis E virus, IL, interleukin, LB, liver biopsy, peg-IFN, pegylated interferon, SVR, sustained virologic response

Conflicts of interest The authors disclose no conflicts.

Funding This study was supported by a grant from Progetti di Ricerca di Interesse Nazionale (PRIN) 2008, Ministero dell'Istruzione e dell'Università e della Ricerca Scientifica, Rome, Italy “Ottimizzazione Della Diagnosi Eziologica dell'epatite Acuta C E Studio dei Fattori Viro-Immunologici di Guarigione, di Cronicizzazione E di Risposta Alla Terapia Con Interferone,” and in part by a grant from Regione Campania “Progetti per il miglioramento della qualità dell'assistenza, diagnosi e terapia del paziente affetto da AIDS nei settori: immunologia, coinfezioni, informazione e prevenzione,” 2008.

PII: S1542-3565(13)00466-7


© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.


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