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Background and Aims: Early post-transplant hepatic fibrosis is associated with poor outcomes and may be influenced by donor/recipient genetic factors. The rs368234815 IFNL4 polymorphism is related to the previously described IL28B polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of this study was to identify the impact of donor and/or recipient IFNL4 genotype on early fibrosis among patients transplanted for hepatitis C (HCV)., Methods: Clinical data were collected for 302 consecutive patients transplanted for HCV. 116 patients who had available liver biopsies and donor/recipient DNA were included. 28% of these patients with stage 2 fibrosis or greater were compared to patients without significant post-transplant fibrosis with respect to clinical features as well as donor/recipient IFNL4 genotype., Results: The IFNL4 TT/TT genotype was found in 26.0% of recipients and 38.6% of donors. Patients who developed early post-transplant fibrosis had a 3.45 adjusted odds of having donor IFNL4 TT/TT genotype (p = 0.012). Donor IFNL4 TT/TT genotype also predicted decreased overall survival compared to non-TT/TT genotypes (p = 0.016)., Conclusions: Donor IFNL4 TT/TT genotype, a favorable predictor of spontaneous HCV clearance pre-transplant, is associated with increased early post-transplant fibrosis and decreased survival., Competing Interests: The authors have declared that no competing interests exist.

Hepatitis C virus infection is prevalent throughout the world and is associated with substantial morbidity, mortality and health economic burden. No effective preventative measure, including vaccination, is currently available. Incremental and substantial progress in the rate of viral eradication using interferon-based therapies has been made over the past decade. The most recent advance has been related to the development of a pegylated form of IFN-alpha by two independent pharmaceutical companies. Pegylation of IFN-alpha appears to prolong its half-life, allowing for less frequent dosing. Reports have suggested that pegylated interferons are also associated with better efficacy for viral eradication in patients with hepatitis C virus. Slower progress also has been made in developing non-interferon-based therapeutic agents against hepatitis C virus, including protease inhibitors, helicase inhibitors, ribozymes, antisense therapies, cytokine-based therapies and T-cell-based therapeutic vaccines.

Objective: The TT virus (TTV) is a novel DNA virus that has recently been identified. The clinical significance of TTV infection in patients with chronic hepatitis C has not been determined. The aim of this study was to determine the prevalence and possible role of TTV in a well characterized population with chronic hepatitis C infection., Methods: Ninety patients with chronic HCV and known time of HCV acquisition were selected from approximately 250 patients followed at our institution. Characteristics including age, sex, histology, and length of disease were recorded. Direct sequencing of the NS5 region was used for HCV genotyping. TTV DNA detection was based on PCR., Results: TTV infection was present in 24 of 90 (27%) HCV patients. Patients were divided into four groups based on stage of disease; chronic hepatitis (CH, 29 patients), compensated cirrhosis (CC, 17 patients), decompensated cirrhosis (DC, 28 patients), and hepatocellular carcinoma (HCC, 16 patients). TTV was present in 2/29 (7%), 2/17 (12%), 11/28 (39%), and 9/16 (56%) in those with CAH, CC, DC, and HCC respectively. TTV was significantly more prevalent among those with advanced disease (DC and HCC) compared to those with stable disease (CH and CC; p = 0.001). Mean age, sex, and the time from exposure to HCV to development of complications were similar in TTV-positive and -negative patients. TTV infection was more common in patients infected with HCV genotype 1b. Univariate analysis showed that length of HCV infection, HCV genotype 1b, and TTV infection were important in predicting the stage of liver disease in HCV patients. However, after adjusting for length of HCV infection, TTV but not HCV genotype was important in predicting the stage of liver disease., Conclusions: We conclude that 1) TTV infection is common in patients with chronic HCV; 2) TTV infection is more prevalent among patients with advanced HCV-associated liver disease (DC and HCC) than in those with stable disease (CH and CC); and 3) TTV infection is more common in patients with HCV genotype 1b but is independent from genotype in predicting the stage of HCV-associated liver disease.

Objective: To correlate viral genotypes with the immune manifestations of chronic hepatitis C and evaluate the effect of immune features on disease expression and response to antiviral treatment., Design: We undertook a retrospective analysis of 67 patients with chronic hepatitis C., Material and Methods: Patients were selected for study if they had been screened for autoantibodies and concurrent immune diseases and if viral genotyping had been performed or was possible. Concurrent immune manifestations and responses to interferon therapy were determined., Results: Of the 67 patients, 18 (27%) had one or more immune features. Immune manifestations occurred as commonly in patients with genotype 1 as in those with other genotypes (30% versus 14%; P = 0.3). Concurrent immune features did not distinguish patients, and responses to interferon therapy were similar between patients with and those without immune manifestations. None of the 14 patients with concurrent immune diseases or high-titer autoantibodies (serum titers, 1:320 or more) entered remission during interferon treatment. In contrast, 6 of 53 patients without concurrent immune diseases and no or low-titer autoantibodies had treatment-related remission. These differences, however, were not statistically significant (0% versus 11%; P = 0.3)., Conclusion: Autoantibodies and concurrent immune diseases are not associated with a particular viral genotype, clinical profile, or treatment outcome. Larger studies are necessary for complete assessment of the influence of prominent immune manifestations on treatment response.

Chronic hepatitis C infection (CH-C) accounts for a significant number of patients undergoing orthotopic liver transplantation (OLT). Recently, hepatitis C virus (HCV) genotype-dependent differences in disease outcome and therapeutic responses have been suggested. The objectives of our study were to determine (1) the recurrence of HCV infection after OLT; (2) distribution of HCV genotypes in patients with CH-C who required liver transplantation compared with those who did not; and (3) the 1-year transplantation outcome in patients infected with different hepatitis C genotypes. RNA was extracted from sera of 20 patients who underwent OLT for end-stage liver disease secondary to CH-C (group I) and 52 patients with CH-C who did not require OLT (group II). For viral RNA detection, reverse transcriptase and polymerase chain reaction (RT/PCR) of 5'UT region was performed on all OLT patients both before and after OLT. For genotyping, RT-PCR of the NS 5 region was performed, followed by automated sequencing of the amplification products. Nineteen OLT patients had viral RNA detected by PCR both before and after OLT. One patient had no RNA detected before OLT but became viremic after OLT. The prevalence of HCV genotype 1b was significantly higher in group I patients compared with group II (53% v 23% respectively, P = .01). Examination of outcome at 1 year after OLT showed that 9 of 10 patients with HCV genotype 1b had histological evidence of hepatitis compared with 4 of 9 patients with other genotypes (non-1b) (P = .06). However, the number of patients who had one or more episodes of rejection, underwent retransplantation, or died at 1 year after OLT were similar. Recurrence of HCV infection after OLT was shown in all studied patients. Hepatitis C genotype 1b is more prevalent in our patients who underwent transplantation compared with a group with chronic hepatitis C who did not require transplantation (P = .01). Patients infected with HCV genotype 1b may have a higher risk of histological hepatitis after transplantation.