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World J Gastroenterol. Jun 14, 2014; 20(22): 6707-6715
Published online Jun 14, 2014. doi: 10.3748/wjg.v20.i22.6707
Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection
Evangelista Sagnelli, Caterina Sagnelli, Mariantonietta Pisaturo, Nicola Coppola
Evangelista Sagnelli, Mariantonietta Pisaturo, Nicola Coppola, Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, 80131 Naples, Italy
Evangelista Sagnelli, Mariantonietta Pisaturo, Division of Infectious Diseases, AORN Sant’Anna e San Sebastiano di Caserta, 81100 Caserta, Italy
Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery “F Magrassi e A Lanzara”, Second University of Naples, 80131 Naples, Italy
Author contributions: Sagnelli E, Sagnelli C, Pisaturo M and Coppola N contributed to the substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the version to be published.
Supported by A grant from PRIN 2008, MIUR, 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
Correspondence to: Evangelista Sagnelli, Professor, Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Vico Luigi de Crecchio, 16, 80131 Naples, Italy. evangelista.sagnelli@unina2.it
Telephone: +39-8-15666271 Fax: +39-8-23232296
Received: September 24, 2013
Revised: January 13, 2014
Accepted: April 1, 2014
Published online: June 14, 2014
Processing time: 264 Days and 17.8 Hours
Abstract

The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Keywords: Chronic hepatitis C virus infection; Hepatic flares; Hepatic flares in immunocompromised patients; Immunocompromised patients; Hepatitis A virus superinfection

Core tip: Patients with chronic hepatitis C virus infection may experience hepatic flares due to an acute exacerbation of this disease that is frequently characterized by a significant increase in liver fibrosis and necroinflammation but by a high rate of sustained viral response to Peg-interferon plus ribavirin treatment. A hepatic flare may also be due to superinfection by other hepatotropic viruses, drug injury or a concomitant autoimmune disease. The aim of this review is to be of some help in identifying the cause of the flare in a single patient in order to optimize the follow-up and clinical and therapeutic decisions.