Recurrence and Management of Hepatitis C after Liver Transplantation / 대한간학회지

BACKGROUND/AIMS: End-stage liver disease caused by viral hepatitis C has been increasing recently in Korea. In this study, we investigated the clinical progress, recurrence, and management of hepatitis C patients who underwent liver transplantation. METHODS: We retrospectively reviewed the clinical progress and management of 16 patients (2.7%) with hepatitis C among 587 liver transplant patients from August 1992 to August 2002. RESULTS: Eleven cases among 16 patients were males. The median age was 56 +/- 6 (42-62) years and the median follow-up period was 6 +/- 13 (1-41) months. Thirteen cases underwent living donor liver transplantation and three had cadaveric whole liver transplantation. Clinical recurrence occurred in nine cases (56.3%) and mean time of recurrence was 5.2 months. Histological recurrence cases were eight (50%). A positive result of HCV RNA PCR was found in 90.9%, and all cases of clinical and histological recurrence in groups in the same periods were PCR-positive. Among eight cases showing histological recurrence, five patients were managed by ribavirin monotherapy, two patients received interferon and ribavirin combination therapy, and one patient was not treated at all. The serum aminotransferase level was normalized in six cases (75%) of them. CONCLUSIONS: We observed that the HCV reinfection rate of a transplanted liver was high in this study, as in other reports in the literature. The prevention of HCV recurrence and the management of post-recurrent cirrhotic change are crucial for graft and patient survival. We think customized protocols are needed for every situation of recurrent hepatitis C.

Immune Response of Peripheral Blood Mononuclear Cells to Core and NS3 Protein in Chronic Hepatitis C Virus (HCV) Infecton / 대한간학회지

BACKGROUND/AIMS: The aims of our study are to assess the frequency of peripheral blood mononuclear cell (PBMC) proliferation and cytokine profiles to hepatitis C virus (HCV) core protein and NS3 protein to search the potential immunosuppressive effect of HCV core in chronically HCV-infected patients. Subjects and METHODS: Thirty two anti-HCV-positive patients with chronic liver diseases, eight HBsAg-positive patients with chronic liver diseases, and six healthy adults were the subjects of our study. Using recombinant HCV core and NS3, proliferative response of PBMC and cytokine production were determined. RESULTS: Fifty nine percent and thirteen percent of patients with HCV-related chronic liver diseases showed positive PBMC proliferation to HCV core and NS3, respectively. Thirty four percent and fifty nine percent of patients with HCV-related chronic liver diseases showed significant production of interferon-gamma to HCV core and NS3, respectively. IL-4 production was negligible. When the PBMC were treated with HCV core and NS3 concurrently, or HCV core and phytohemagglutinin concurrently, the stimulation indices were significantly decreased compared to those treated either with NS3 or PHA without core. CONCLUSIONS: Although about two thirds of chronically HCV-infected patients with liver diseases showed the PBMC proliferation and Th 1 type cytokine profile, they could not eradicate the viral infection. This ineffective immune response seems to play a role in the pathogenesis of chronic inflammatory liver disease resulting in liver cirrhosis and hepatocellular carcinoma. HCV core showed a potential immunosuppressive effect, which has important meaning for the mechanism of HCV persistence.

Quantitation of Hepatitis C Virus RNA by Competitive RT-PCR and DNA-ELISA Method / 대한간학회지

BACKGROUND/AIMS: Quantitation of Hepatitis C Virus (HCV) RNA in serum is important for monitoring the response to interferon-alpha therapy in patients with chronic hepatitis C. Several commercial assays are recently available, but they are expensive and cannot be used as a gold standard. METHODS: An in-house competitive reverse transcription-polymerase chain reaction (cRT-PCR) was developed and validated. The procedure involves the construction of a mutant and wild type HCV RNA internal standard (IS), cRT-PCR, and colorimetric detection with DNA-ELISA. A standard curve was obtained and used for final HCV RNA quantitation. RESULTS: The standard curve was linear over the range of 1x104 to 5x107 copies/mL of the HCV RNA standard (r=0.976). This in-house cRT-PCR was comparable with the branched DNA (bDNA) assay (Quantiplex HCV 2.0, Chiron, USA) with positive correlation between the two tests (r=0.735). CONCLUSION: The quantitation of HCV RNA by in-house cRT-PCR and DNA ELISA was more sensitive and had wider range of detection compared to bDNA assay. This assay is useful for follow-up of HCV RNA concentration after interferon-alpha therapy.