Liver biopsy, viral kinetics, and the impact of viremia on severity of hepatitis C virus recurrence

Abstract

A lthough the impact of hepatitis C virus (HCV) infection on allograft histology varies substantially, 1-7 allograft failure secondary to recurrence of HCV is the most common cause of death and retransplantation among recipients with HCV. 8 In HCV and in other viral infections, including HIV 9 and hepatitis B, 10 analysis of viral dynamics has not only been helpful in understanding pathogenesis of infection but also in determining responsiveness to therapies. To date there have been relatively few studies of detailed viral kinetics after liver transplantation.All of the HCV kinetics studies that have been carried out to date have been in the nontransplantation setting and have relied on indirect measures of viral turnover incorporating mathematical models that are dependent on assumptions regarding the number of infected hepatocytes, interferon mechanisms of action, and efficacy. [11][12][13][14][15] Although these studies have undoubtedly provided insight into HCV kinetics, the reported half life (t 1/2 ) of hepatitis C virions has varied greatly among studies. Neumann et al reported the virion t 1/2 to be 2.7 hours, with production and clearance rates of 10 12 virions/day. 12 In contrast, Zeuzem et al reported the t 1/2 of hepatitis C to be 64.8 hours and clearance rates to be 6.7 ϫ 10 10 virions/day. 14 Both the Neumann and Zeusem manuscripts include discussions of the limitations of the techniques and models that were used, including the inability to discriminate between inhibition of HCV uptake into hepatocytes and inhibition of HCV RNA replication in de novo infected cells. In addition, all reports of HCV dynamics have relied on the serial determination of HCV RNA levels as a surrogate of HCV synthesis. Inherent to these methods is the unproven and unlikely assumption that viral synthesis is completely inhibited after initiation of interferon therapy. These limitations notwithstanding, important insights into the natural history of posttransplantation HCV infection can be distilled from the analysis of posttransplantation viral kinetics. The Impact of Liver Transplantation on Levels of Hepatitis C Viremia Early KineticsAlthough the interval between liver transplantation and clinical allograft infection varies, negative-strand HCV RNA, the putative sine que non of HCV replication, has been detected very early in the posttransplantation course. 16,17 Using a semiquantitative strand-specific reverse transcriptase-polymerase chain reaction in 23 liver transplant recipients with HCV infection, Negro et al were able to detect intrahepatic negative-strand HCV RNA as early as 7 days after liver transplantation. 17

Pattern of Recurrent Hepatitis C in Deceased vs Living Donor Liver Transplantation: An Egyptian Experience

“…The higher level and activity of HCV may be due to rapid regeneration of the liver in LDLT group making the cells more prone to reinfection and their activity enhances the viral introduction and replication. 21 Immunosuppression is considered a main factor in the severity of recurrent HCV infection, 22,23 because of its effect on viral replication and its suppression of systemic immune responses, both of which can lead to accelerated KHSDWRFHOOXODU GDPDJH DQG ¿EURVLV In our study, tacrolimus and cyclosporine were not associated with HCV recurrence. Cyclosporine had antiviral properties in vitro DQG ZDV DVVRFLDWHG ZLWK D VLJQL¿FDQWO\ lower risk of recurrence of HCV 24 and less fibrosis.…”

Recurrent Hepatitis C Virus (Genotype 4) Infection after Living Donor Liver Transplantation: Risk Factors and Outcome

“…Immunosuppression is considered a main factor in the severity of recurrent hepatitis C virus infection [16], because of its effect on viral replication and its suppression of the systemic immune responses, both of which can lead to accelerated hepatocellular damage and fibrosis. So, modifying immunosuppression are the main means of preventing disease progression [2].…”

Hepatitis C treatment before and after liver transplant

“…In all of these cases, however, the real recurrence rate can only be estimated through routine serial biopsies, considering that 20% to 30% of patients do not evolve to increased aminotransferase levels, and that such an increase lacks specificity, potentially resulting from other events, such as rejection, ischemia or opportunistic infections [8]. In the Liver Transplant Sector of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP, University of São Paulo School of Medicine Hospital das Clínicas), protocol biopsies are carried out every six months in the first year after the transplant, every year between the second and forth year after the transplant, and every three years after the sixth year of the transplant.…”