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Re: HCV genotype 2 as risk factor for reactivation of chronic HCV infection

Dear Editor,

Little information is available in the literature on the acute exacerbation of chronic hepatitis C (r-CHC) [1-6]. In Taiwan, Dr. Sheen estimated an annual incidence rate of 11.9% [3]. In this study 40.2% of 78 patients experienced at least one episode of reactivation during a mean observation period of 6 years and a total of 151 episodes of reactivation were observed, 45% of them symptomatic. The paper by Dr. Rumi from Milan [5], recently published in Gut, on r-CHC in relation to HCV genotyping described it as frequent in patients with genotype 2c (39% of 100 patients) and infrequent in those with genotype 1b (7.5% of 106 patients), with a rate x 1,000 persons/year of 55.6 and 15.0, respectively. From January 2002 to date we have enrolled in a prospective follow-up study 49 consecutive patients with acute hepatitis C (AHC group) and 57 consecutive patients with r-CHC (r-CHC group). All patients were hospitalised at our ward because the illness was symptomatic.

The criteria for a diagnosis of AHC were: a) negative serum anti-HCV and normal alanine-aminotransferase (ALT) serum values in the 4 months preceding the onset of symptoms; b) positive anti-HCV/HCV-RNA and increased ALT (>5 times the highest value of normal) during the acute stage of the illness. The diagnosis of r-CHC was made for patients with: a) positive serum anti-HCV and plasma HCV-RNA during the 6 months before the onset of symptoms and on admission; b) ALT increase >5 times the mean of the ALT values observed during the previous six months. As a control group for the patients in the r-CHC group, 57 HBsAg negative, symptom-free, untreated patients with chronic hepatitis C (CHC Group), hospitalised in the same period for their first liver biopsy, were pair- matched by age (+/- 5 years), sex and risk factor for the acquisition of parenteral infection.

All patients in the AHC and r-CHC groups lacked serum HBsAg, anti-HBc IgM, anti-HDV, anti-HAV IgM and IgM to the herpes viruses. Excluded were patients treated with Interferon + Ribavirin in the last 24 months, anti HIV positive subjects, those with a history of alcohol abuse and those treated with potentially hepatotoxic drugs. Plasma HCV-RNA was determined by qualitative Reverse Transcriptase-PCR (HEPA-Check-C, Nuclear Laser Medicine) and HCV genotyping by Line-Probe- Assay (INNO-LIPA HCV II, Innogenetics). Anti-HCV, anti-HIV, HBV and HDV serum markers were sought using a commercial immunoenzymatic assay. The statistical analysis of the results was made applying the chi square test with the Yates correction; a p value <0.05 was considered statistically significant.

HCV genotype 2 was more frequently found in patients in the r-CHC group (35.1%) than in those in the AHC group (8.2%, p<0.005) or the CHC group (14%, p<0.05). Conversely, HCV genotype 1 was detected less frequently in the r-CHC group (49.1%) than in the AHC (67.3%) or CHC group (65%) (p>0.1). The observation that patients with a symptomatic acute exacerbation of chronic hepatitis C harbour HCV genotype 2 more frequently than asymptomatic chronic hepatitis patients and than patients with acute hepatitis C is in good agreement with the more frequent occurrence described by Dr Rumi in Gut of r-CHC, mostly asymptomatic, in the patients with HCV genotype 2c than in those with HCV genotype 1b [5]. The available data seem to indicate that, whether the clinical presentation is symptomatic or asymptomatic, an acute exacerbation of chronic hepatitis C is associated to an HCV genotype 2 chronic infection. However, a multicentre prospective study is needed to acquire more conclusive data.

Nicola Coppola (1,2), Luisa Maria Vatiero (1,2), Evangelista Sagnelli (1,2)

1: Division of Infectious Diseases, San Sebastiano Hospital, Caserta, Italy

2: Department of Public Medicine, Section of Infectious Diseases, 2nd University of Naples

Correspondence:
Prof. Evanglista Sagnelli
Department of Public Medicine
Section of Infectious Diseases
Second University of Naples
c/o Ospedale Gesł e Maria
via D. Cotugno 1
80135, Naples
ITALY
Tel +39 81 5666202
Fax: +39 81 5666214;
e-mail: evangelista.sagnelli{at}unina2.it

Acknowledgments: This study was supported by a grant from Ministero della Salute, D.Leg.vo 229/99, E.F. 2000; MIUR, Cofinanziamento 2003.

References

1. Jarvis LM, Watson HG, McOmish F, Peutherer JF, Ludlam CA, Simmonds P. Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs. J Infect Dis 1994; 170: 1018-1022.

2. Kao JH, Chen PJ, Lai MY, Yang PM, Sheu JC, Wang TH, Chen DS. Mixed infections of hepatitis C virus as a factor in acute exacerbations of chronic type C hepatitis. J Infect Dis 1994; 170:1128-1133.

3. Sheen IS, Liaw YF, Lin DY, Chu CM. Acute exacerbations in chronic hepatitis C: a clinicopathological and prognostic study. J Hepatol 1996; 24: 525-531.

4. Rumi MG, De Filippi F, Donato MF, Del Ninno E, Colombo M. Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough. J Viral Hep 2002; 9: 71-74.

5. Rumi MG, De Filippi F, La Vecchia C, Donato MF, Gallus S, Del Ninno E, Colombo M. Hepatitis C reactivation in patients with chronic infection with genotype 1b and 2c: a retrospective cohort study of 206 untreated patients. Gut 2005; 54: 402-406.