Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients

Abstract

Background: We previously described hepatitis reactivation in two carriers of the hepatitis C virus (HCV) genotype 2c. Aim: To assess the relationship between HCV genotypes and risk of hepatitis reactivation, we studied the course of aminotransferases in patients infected with the two relevant genotypes in Italy. Patients: A cohort of 100 patients with genotype 2c chronic hepatitis and 106 with genotype 1b were subjected to surveillance. Methods: Hepatitis reactivation was defined as an alanine aminotransferase (ALT) value >400 IU/l or a maximum/minimum ALT ratio value of >8. Results: Over a period of 71 (24-144) months, one or more flares of ALT (201-2200 IU/l, 6-90 months' duration) occurred in 31 patients with genotype 2c and in eight patients with genotype 1b (rates of flares: 55.6 per 1000 person years for genotype 2c v 15.0 for genotype 1b; p = 0.001). On repeat biopsy, hepatic fibrosis increased by more than 2 points in 10/16 patients examined either during or after an ALT flare compared with 7/36 flare free patients (63% v 19%; p = 0.003). Hepatitis flares were significantly associated with genotype 2c (odds ratio 6.48 (95% confidence interval 2.57-16.35)) but not with sex, age, modality or duration of infection, baseline ALT values or histological severity of hepatitis, hepatitis other than HCV, or reinfection. Conclusions: Genotype 2c carriers are at high risk of hepatitis reactivation, suggesting that virus genetic heterogeneity is important in the natural history of HCV, questioning the linearity of hepatic fibrosis progression during hepatitis C.

Hepatitis C Virus (HCV) Reactivation Caused by Steroid Therapy for Dermatomyositis

“…To our knowledge, this is the first report of HCV reactivation caused by a single administration of steroid therapy for collagen disease. HCV reactivation is associated with the use of various immunosuppressive and chemotherapeutic agents, including busulfan, cytarabine, cyclosporine, gemcitabine, methotrexate, rituximab and vincristine (5)(6)(7)(11)(12)(13)(14)(15)(16). Many patients who exhibit HCV reactivation during treatment with one of these drugs are simultaneously treated with corticosteroids (11,12).…”

“…In contrast to that observed for HBV, the frequency of HCV reactivation is low. HCV reactivation may occur as a consequence of the loss of host immune control over the virus (4,5); however, little is known about the overall frequency and mechanisms of HCV reactivation (6). HCV reactivation is commonly defined as a threefold or greater increase in the serum alanine aminotransferase (ALT) level in patients without tumor infiltration to the liver who have not received hepatotoxic drugs and have no recent history of blood transfusions or other systemic infections in addition to HCV.…”

Changes in risk behavior and dynamics of hepatitis C virus infections among young drug users in Amsterdam, the Netherlands

“…Moreover, HCV-genotyping provides important clinical information with regard to both disease progression and treatment. For example, genotypes 2 and 3 show higher rates of hepatitis reactivation and steatosis, but on the other hand, they have a significantly higher sustained virological response and require a shorter period of treatment than genotypes 1, 4, 5, and 6 [Hofer et al, 2002;Poynard et al, 2003;Rumi et al, 2005].…”

Do Hepatitis C Virus Genotypes Influence Liver Dysfunction following Rituximab-Containing Regimens in Patients with Diffuse Large B Cell Lymphoma?

“…It is possible that they are incidental. However, some published data show a higher incidence of hepatitis flare in HCV genotype 2 patients compared with that in genotype 1 patients [8][9][10] . The hypervariable region 1, part of the HCV envelope glycoprotein E 2 , carries epitopes targeted by the host immune system [16] .…”