Graft Hepatitis Research Articles

Pediatric Liver Transplantation: Selection Criteria and Post-transplant Medical Management.

Pediatric liver transplantation remains the gold standard for life-threatening acute and chronic liver diseases and multiple liver-based inherited metabolic defects. Advances in surgical techniques, better perioperative care and immunosuppression regimes have resulted in excellent long-term graft and patient survival. The success of pediatric liver transplantation does however bring the additional challenge of long-term patient outcomes including graft hepatitis-related fibrosis and suboptimal biopsychosocial outcomes. In this review, authors will explore the current landscape of pediatric liver transplantation including indications, timing of referral for liver transplantation, surgical techniques and long-term outcomes such as recurrence of pre-transplant liver disease, idiopathic graft hepatitis and biopsychosocial outcomes. Ultimately, early identification and management of potential issues long-term helps ensure our recipients achieve a "meaningful survival".

The role of immunosuppression in long-term graft hepatitis and fibrosis after paediatric liver transplant - comparison of two treatment protocols.

We have previously demonstrated high rates of chronic allograft hepatitis and fibrosis in liver transplant patients on long-term cyclosporine monotherapy. We subsequently changed practice to add low-dose prednisolone to maintenance treatment with tacrolimus post-transplant. The aim of the study was to assess the impact of the immunosuppression change on graft histopathology. Patients treated in this era (Tac + Pred, 2000-2009, N = 128) were compared to a historical cohort, who had been maintained on a steroid-free, cyclosporine-based regime (CSA-Only, 1985-1996, N = 129). Protocol liver biopsies and laboratory tests were performed five- and ten-years post-transplant in both groups. Compared to CSA-Only, the Tac + Pred cohort had significantly lower rates of chronic hepatitis (CH) at five (20% vs. 44%, p < 0.001) and ten (15% vs. 67%, p < 0.001) years post-transplant, with similar trends observed in inflammation and fibrosis at five years. The Tac + Pred cohort also had significantly lower hepatic transaminases and IgG levels and was less likely to be autoantibody positive at both time points. However, the degree of graft fibrosis at ten years did not differ significantly between eras (p = 0.356). Increased immunosuppression effectively reduced chronic allograft hepatitis and fibrosis at five years, suggesting it is an immunologically driven variant of rejection. However, there was no significant reduction in the degree of fibrosis at ten years, indicating a multifactorial origin for long term graft fibrosis.

Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance.

Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.

Hepatitis B Vaccination in Patients Receiving Oral Antiviral Therapy Without Hepatitis B Immunoglobulin After Liver Transplant

Our study aimed to determine if a double-dose pre-S containing hepatitis B virus (HBV) vaccination (Sci-B-Vac) could elicit an adequate and sustainable immune response in HBV patients who developed spontaneous hepatitis B surface antibody (anti-HBs) response after liver transplant. Patients and MethodsAll patients who received transplants for HBV-related disease for >1 year with normal graft function and hepatitis B surface antigen seronegativity were evaluated. They received a 40-μg HBV vaccine if they were responders in our previous vaccine trial, if anti-HBs was positive for >1 year after liver transplant (LT), or if a peak anti-HBs at any time point after LT was >100 mIU/mL. Primary endpoint was the development of anti-HBs ≥ 10 mIU/mL from previous negative value or a 1-log increase from baseline. ResultsA total of 86 patients were recruited; 5 were responders from a previous trial; 45 patients had detectable anti-HBs >1 year after LT, and 36 patients had an anti-HBs >100 mIU/mL. All (5/5, 100%) previous responders responded to booster vaccination. For the remaining 81 patients, 10 of 81 (12.3%) responded. ConclusionAll previous responders responded to booster vaccination, implying durability and memory of HBV immune response, which is an important prerequisite for definitive host immunity for HBV. In patients who had spontaneous anti-HBs production after LT, a single vaccination can induce response in 12.3% of patients.

Late graft hepatitis and fibrosis in pediatric liver allograft recipients: Current concepts and future developments

Liver transplantation (LT) in children now has a 20-year survival of >80%, but the longterm outcome of these grafts remains uncertain. Serial protocol liver biopsies after transplantation from several pediatric centres have demonstrated the gradual development of unexplained graft inflammation ("idiopathic" posttransplant hepatitis; IPTH) and graft fibrosis in biopsies obtained >12 months post-LT in children with good graft function and (near) normal liver biochemistry. Although the clinical significance of these findings is uncertain, there is evidence to suggest that IPTH may be a form of rejection or chronic antibody-mediated rejection as it is associated with the presence of auto/alloantibodies; de novo Class II donor-specific HLA antibodies (DSA); previous episodes of rejection, and may improve or be prevented with increased immunosuppression. Currently, the only method of diagnosing either hepatitis or fibrosis has been by serial protocol biopsies as neither serum markers of fibrosis nor noninvasive methods to detect fibrosis such as transient elastography (TE) are sufficiently validated in children. This review will focus on the diagnosis and management of idiopathic posttransplant hepatitis and graft fibrosis, discuss current methods for detecting graft injury, and potential mechanisms for their development. Liver Transplantation 22 1593-1602 2016 AASLD.

D-MELD, the Product of Donor Age and Preoperative MELD, Predicts Surgical Outcomes After Living Donor Liver Transplantation, Especially in the Recipients With HCV-positive and Smaller Grafts

BackgroundAppropriate donor-recipient match has not been explored well in living-donor liver transplantation (LDLT) unlike deceased-donor liver transplantation. In this study, we evaluate the donor-recipient match using D-MELD (donor age × recipient Modified for End-stage Liver Disease [MELD] score) as a predictor of surgical outcomes in LDLT, paying attention to graft size and hepatitis C virus (HCV) status. Patient and MethodsThe 120 consecutive recipients who received adult-to-adult LDLT from March 2002 to December 2014 were divided into the two groups according to D-MELD score: D-MELD <1000 (low-D-MELD: n = 101) and D-MELD ≥1000 (high-D-MELD: n = 19). ResultsThe 90-day mortality rate was significantly higher in the high-DM group than in low-DM group: 36.8% versus 14.9% (P = .046). In the HCV-positive recipients, the 90-day mortality rate was significantly higher in high-DM group (n = 6) than in low-DM group (n = 37): 66.7% versus 13.5% (P = .012), and the 3-year survival rate was significantly lower in high-DM group than in the low-DM group: 33.3% versus 56.8% (P = .01). In the recipients with left graft, the 90-day mortality rate was significantly higher in the high-DM group (n = 8) than in the low-DM group (n = 41): 50% versus 14.6% (P = .044), and total bilirubin level on postoperative day 14 was significantly higher in the high-DM group than in the low-DM group: 17.4 mg/dL versus 9.2 mg/dL (P = .018). ConclusionsIt was clarified that D-MELD could predict early and long-term surgical outcomes in the recipients who were HCV-positive and who had smaller grafts.

Hepatitis E virus infection in the liver transplant recipients: Clinical presentation and management.

Hepatitis E virus (HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.

Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation.

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

Management of chronic hepatitis B before and after liver transplantation.

Liver transplantation remains the only curative option for eligible patients with complications of chronic hepatitis B (CHB) infection, including severe acute hepatitis flares, decompensated cirrhosis, and hepatocellular carcinoma. In general, all patients with CHB awaiting liver transplantation should be treated with oral nucleos(t)ide analogs (NAs) with high barriers to resistance to prevent potential flares of hepatitis and reduce disease progression. After liver transplantation, lifelong antiviral therapy is also required to prevent graft hepatitis, which may lead to subsequent graft loss. Although combination therapy using NA and hepatitis B immune globulin (HBIG) has been the regimen most widely adopted for over a decade, recent studies have demonstrated that newer NAs with low rates of resistance are effective in preventing graft hepatitis even without the use of HBIG, achieving excellent long term outcome. For patients without pre-existing resistant mutations, monotherapy with a single NA has been shown to be effective. For those with resistant strains, a combination of nucleoside analog and nucleotide analog should be used. To date, clinical trials using therapeutic vaccination have shown suboptimal response, as CHB patients likely have an immune deficit against HBV epitopes. Future strategies include targeting different sites of the hepatitis B replication cycle and restoring the host immunity response to facilitate complete viral eradication.

Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus-related end-stage liver disease.

Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)-infected liver transplant recipients. Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy-related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed. Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH-C. Liver biopsy in HCV-infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.

The impact of hepatitis E in the liver transplant setting

Hepatitis E virus (HEV) infection has been identified as a cause of graft hepatitis in liver transplant recipients. The true frequency and clinical importance of HEV infections after liver transplantations is a matter of debate. It is proposed that consumption of HEV-contaminated undercooked meat is a main source for HEV infections in developed countries--which might also account for some hepatitis E cases after organ transplantation. However, HEV is also transmitted by transfusion of blood products, likely representing a previously underestimated risk particularly for patients in the transplant setting. HEV infection can take chronic courses in immunocompromised individuals, associated in some cases with rapid progression to cirrhosis within 1-2 years of infection. Diagnosis in transplanted patients is based on HEV RNA testing as antibody assays are not sensitive enough. Selection of immunosuppressive drugs is important as different compounds may influence viral replication and the course of liver disease. Ribavirin has antiviral activity against HEV and should be administered for at least three months in chronically infected individuals; however, treatment failure may occur. HEV infections have also been linked to a variety of extrahepatic manifestations both during and after resolution of infection. In this review we summarize the emerging data on hepatitis E with a particular focus on the importance of HEV infections for liver transplant recipients.

Predictability and Survival in Liver Replantransplantation: Monocentric Experience

Liver retransplantation is the only treatment for patients with hepatic graft failure. Due to the shortage of organs, it is essential to optimize its use. Between 1998–2010, our center performed retransplantations on 48 (12.8%) patients (re-OLT). The data are compared with those for a group of 374 patients who did not receive retransplantations (NO re-OLT). The re-OLT vs NO re-OLT groups did not significantly differ in mean age of recipients (47 vs 51 years), indications for transplantation (hepatitis C virus cirrhosis 54% vs 56%, alcoholic cirrhosis 25% vs 17%, hepatocellular carcinoma 14% vs 22%), mean Model for End-stage Liver Disease (25 vs 20), mean total cold ischemia time (385 vs 379 minutes), or mean age of donors (52 vs 49 years). The main causes of retransplantation were primary graft nonfunction (64%), arterial thrombosis (8%), biliary complications (6%), and hepatitis C virus recurrence (4%). The difference in overall patient survival was not statistically significant. The patient's survival at 1, 3, 5, and 10 years for RE-OLT vs NO-reOLT was 56% vs 63%, 53% vs 60%, 46% vs 57%, and 44% vs 53%, respectively. Multivariate analysis identified Model for End-stage Liver Disease ≥23 as a predictor factor of retransplantation (P = .04). Other variables predicting outcome included age of donors (≥65 years vs younger group), age of recipients (≥50 years vs younger group), cold ischemia (≥600 vs <600 minutes), and transplantation indications (hepatitis C virus, hepatitis B virus, alcohol, and others). The retransplantation performed between 8–15 days appeared to have worse results than those in other periods (0–7 days, 16–30 days, 1–6 months, >6 months). The incidence of re-OLT in the series (12.8%) was comparable to that in the literature, and primary graft nonfunction in the study represents the main cause of retransplantation. Our analysis showed that the indication of the first transplant and the age of the donor were not risk factors for re-OLT. Liver retransplantation is a concrete alternative lifesaver for patients with graft failure.

Outcomes of Kidney Transplantation Recipients With Hepatitis in the Antiviral Therapy Era: A Single-Center Experience

IntroductionThe use of organs from hepatitis B surface antigen (HBsAg)+ donors could increase the donor pool substantially. However, fulminant hepatic failure requiring urgent liver transplantation or resulting in death has been reported in recipients of HBsAg+ renal transplantation (KT) in pre-nucleos(t)ide analog (NA) era. With effective antiviral therapies such as NAs, it seems feasible to transplant such recipients more safely. To address this issue, we conducted a retrospective, cohort study to evaluate the safety and long-term risks of HBsAg+ KT recipients in the NA era. MethodsFrom December 2006 to January 2013, 112 patients undergoing KT were followed at our institute. We analyzed patient and graft outcomes, hepatitis status (HBsAg status, hepatitis B virus [HBV] DNA level, liver function tests, presence of hepatitis C virus [HCV] co-infection), and graft source (domestic or transplant tourism). ResultsNinety-two KT recipients were still alive. Nine patients were died of nonhepatic factors. Among 112 patients, there were 19 of 92 recipients alive who were HBsAg+, including 6 patients with HBV and HCV dual infections. Two of 19 patients experienced symptomatic hepatitis, one de novo and the other re-activation. Liver functions of these 2 recipients recovered progressively after introduction of NAs. No recipients in our study had experienced graft loss at the time of analysis. ConclusionIn terms of patient survival and quality of life, KT seems be a safe and feasible therapy of choice for HBsAg+ patients with end-stage renal disease. Infection is easier to prevent than to treat. KT recipients at high risk for HBV reactivation and for complications of HBV, with or without HCV co-infection, may benefit from longer prophylaxis. However, the optimal duration of prophylaxis remains unclear. Furthermore, several issues needed to be solved for clinical concerns, such as frequency and intensity of adverse effects, high costs, increased pill burden, drug–drug interactions, and the emergence of viral resistance variants.

Hepatitis E infection in liver transplant recipients

Hepatitis E virus (HEV) infection (genotype 3) has been described in developed countries as a cause of chronic hepatitis in recipients of solid organ transplantation (SOT), with the first cases reported in 2008. Immunosuppression seems to play a major role in the pathogenesis of chronic infections. The current gold standard for the diagnosis of HEV infection is the detection of HEV RNA in serum, stools, or both. In liver transplant recipients, HEV infection is considered an uncommon disease; however, a high index of suspicion is needed for patients with graft hepatitis of an unclear etiology. Liver transplant recipients seem more likely to develop chronic HEV after an acute infection, and there is accelerated progression to advanced fibrosis and cirrhosis. A decrease in immunosuppression is considered the first line of treatment, and pegylated interferon can be considered the second line of treatment for liver transplant recipients. At the present time, there are not enough data to recommend treatment with ribavirin for adult liver transplant recipients, although this has been tried in other SOT populations.

Acute Hepatitis With Periportal Confluent Necrosis Associated With Human Herpesvirus 6 Infection in Liver Transplant Patients

To correlate human herpesvirus 6 (HHV-6) viral load with pathologic features in graft acute hepatitis of unknown origin. Liver frozen samples from 26 patients with graft hepatitis of unknown origin were available for HHV-6 DNA quantification. In 10 (38.5%) of 26 liver samples, HHV-6 DNA was detectable, with a median viral load of 3.84 log10 copies/10⁶ cells. Confluent periportal necrosis was observed in 4 of 10 patients and associated with high viral load. These 4 patients responded to antiviral therapy. Mild unspecific hepatitis was observed in 4 patients with low intragraft viral load and in 2 patients with high viral load in a context of deep immunosuppression. Patients with HHV-6-negative graft hepatitis disclosed lobular necrotico-inflammatory activity without periportal necrosis. Our study provides data supporting the pathogenic role of HHV-6 for liver allografts. The presence of confluent periportal necrosis could be a clue for prompt diagnosis of HHV-6-induced graft hepatitis.

Liver biopsy post liver transplantation for HCV-related end stage liver disease: Clinical value and risk factors for graft hepatitis and rejection

Background and aim: Hepatitis C-related end stage liver disease (HCV-ESLD) is the leading primary indication for liver transplantation (LT). Recurrent HCV infection after LT is universal and most patients show manifested graft hepatitis. Accurate diagnosis is important in acute rejection in HCV-infected patients, as increased immunosuppression accelerates HCV-induced liver damage and shortens graft and patient survival. Aim of our study was to investigate the safety and the clinical value of this procedure in a large academic referral European LT center.

Clinical relevance of GSTT1 mismatch in solid organ and hematopoietic stem cell transplantation

Since 2001, year in which Glutathione S-transferase theta class 1 (GSTT1) gene appeared to be related to the occurrence of de novo immune hepatitis after liver transplantation, this gene with two allelic variants, GSTT1(∗)A (wild type copy) and GSTT1(∗)0 (deletion copy), has emerged as a potent histocompatibility antigen. Namely, a donor-recipient liver graft combination of a GSTT1-negative recipient (homozygous for GSTT1(∗)0) and a GSTT1-positive donor results, very frequently, in the appearance of a severe immune-related graft hepatitis with production of IgG anti-GSTT1 antibodies. In kidney transplantation, GSTT1 donor-recipient mismatch is also associated with production of anti-GSTT1 antibodies and antibody-related rejection episodes with C4d deposition in graft biopsy. The more recent discovery of anti-GSTT1 antibodies in hematopoietic stem cell transplantation, clearly confirms a role of GSTT1 as histocompatibility antigen in this setting. Interestingly, the consequences of GSTT1 mismatch might be either rejection or graft-versus-host disease, depending on the GSTT1 mismatch's sense of direction. The involvement of GSTT1 in immunological allo-recognition is unquestionable although there are still many aspects that remain to be explored.

The Long-Term Outcomes of Patients Transplanted Due to Acute Liver Failure With Hepatic Human Herpesvirus-6 Infection

Human herpesvirus (HHV)-6, comprised of HHV-6A and HHV-6B, belongs to the betaherpesviruses that infect 95%–100% of humans. Primary infection, known as exanthema subitum, occurs in early childhood. Reactivations of latent HHV-6, mostly HHV-6B, are common after liver transplantation. The vast majority of them are asymptomatic; in a minority of cases, the virus may infect the liver transplant, causing graft dysfunction or hepatitis. An association between hepatic HHV-6 infection and indeterminate acute liver failure (ALF) has been shown, but the causality is not clear because of the ubiquitous nature of HHV-6. We have previously observed HHV-6B antigens in the explanted livers of most patients (80%, n = 32) transplanted with ALF of unknown cause, whereas it was not observed among those with ALF of known cause. After transplantation, half of the patients with pretransplant HHV-6 infection (9/18) developed recurrences. The aim of this study was to investigate their long-term course (9–14 years). Half of the patients with pretransplant HHV-6 developed recurrences. Two also showed cytomegalovirus (CMV) hepatitis, whereas none of the other patients demonstrated intrahepatic CMV. During the 9 years or more of follow-up, 1 graft and 2 patients were lost in both groups (HHV-6 recurrence/HHV-6-negative patients). The reasons for graft loss were hepatic arterial thrombosis and portal venous thrombosis. In addition 2 patients died in the HHV-6 recurrence group, one because of rethrombosis of hepatic artery (day 460) and one with a functioning transplant (4.5 years after transplantation). In the control group 1 patient died at 1.5 years and 1 at 10 years after liver transplantation because of pneumonia. HHV-6 relapse was common in ALF patients after transplantation. However, HHV-6 did not cause liver failure and had no significant long-term effect on survival.

Results of single‐center screening for chronic hepatitis E in children after liver transplantation and report on successful treatment with ribavirin

RNA screening for HEV in 22 liver-transplanted children with chronic graft hepatitis out of a cohort of 267 liver-transplanted children detected a single patient with chronic HEV infection. Although this patient remained viremic for 33months, anti-HEV-IgG was not detectable with MP assay but with Wantai assay. We present the first case of successful ribavirin therapy in an immunosuppressed child with chronic HEV infection. In conclusion, chronic HEV infection in immunosuppressed children may not be detectable employing serological assays. Therefore, the most reliably screening method is screening for HEV-RNA. Chronic HEV infection in children can successfully be treated with ribavirin.

Prognostic serum biomarkers for graft survival after liver transplantation in hepatitis C patients

Graft reinfection in liver transplanted patients with chronic hepatitis C (HCV) is almost universal leading to severe fibrosis and graft loss in 25–35% of the patients in the first five years after transplantation. As the currently available antiviral therapy is associated with severe side effects and rejection episodes, prognostic factors that can identify patients at risk for graft dysfunction and graft loss are urgently needed. We hypothesized that distinct immunological markers may predict the long-outcome of graft hepatitis C.