PRURITUS AND HLA IN HEMODIALYSIS PATIENTS

Hepatitis C virus (HCV) infection is known to increase morbidity and mortality in the dialysis population. Renal transplantation is an offered treatment option after a careful pretransplant evaluation. This study assessed the impact of HCV infection on patient and allograft survival rates in a selected group of dialysis patients and kidney transplant recipients.
The study included 252 end-stage renal disease patients who were receiving hemodialysis (HD) treatment or who received renal transplantation at our centre in 1995–96. Of the total, 116 [94 HCV (–) and 22 HCV (+)] underwent transplantation and 134 [106 HCV (–) and 30 HCV (+)] remained on HD. We retrospectively investigated 5 years of follow-up findings in the records of these patients. All 22 HCV (+) individuals underwent liver biopsy to ensure there was no advanced liver disease before transplantation. None of the recipients or HD patients showed decompensation related to liver disease during follow up.
The overall 5-year patient survival rates for the kidney recipient and HD groups were 85.2% and 74.5%, respectively. Comparison of outcomes for the HCV (+) recipients had a significantly higher 5-year survival rate than the HCV (+) HD patients ( P <0.04). The 3-year graft survival rates for the HCV (+) and HCV (–) transplant recipients were comparable, but the risks of chronic rejection and graft loss at 5 years were higher in the HCV (+) group ( P <0.02, P <0.006, respectively). In conclusion, renal transplantation should be the preferred therapy in HCV-infected dialysis patients because it improves the survival rates. HCV infection is associated with increased rates of chronic rejection and graft loss at 5 years post-transplantation.     

Hepatitis C virus infection in haemodialysis and kidney transplant patients

Chronic infection with hepatitis C virus (HCV) is an important global health problem. The prevalence of HCV is significantly higher in haemodialysis and kidney transplant patients, as compared to the general population. In spite of the relatively milder liver disease activity reported in HCV-infected haemodialysis patients, HCV infection adversely affects survival. Likewise, HCV has a detrimental effect on both patient and graft survival after kidney transplantation. However, patient survival is significantly better with kidney transplantation compared to remaining on dialysis; therefore, HCV infection alone should not be a contraindication to transplantation. Combination antiviral therapy with pegylated interferon-alpha and low-dose ribavirin is currently evolving in haemodialysis patients. Interferon-alpha (standard/pegylated) is relatively contraindicated after kidney transplantation because of an increased risk of allograft rejection. Therefore, antiviral treatment of transplant candidates while on dialysis remains the best option and may avoid the risk of HCV-associated liver and renal disease after transplantation. Large multi-centre clinical trials are required in HCV-infected haemodialysis and kidney transplant patients in order to define optimal therapeutic strategies before and after transplantation.     

Treatment of recurrent HCV infection after liver transplantation

End-stage liver disease associated with hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation (OLT) and accounts for 50% of these procedures in Spain and 42% of OLT performed in the United States. Recurrent infection with HCV after OLT, however, is almost universal and is associated with substantial morbidity, mortality, and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following OLT. By the fifth postoperative year, over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 30% developing cirrhosis. While the choice of calcineurin inhibitor has not been clearly shown to affect the histologic recurrence of hepatitis C or the frequency of rejection in HCV-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histologic recurrence. There have been no well-controlled, large, prospective, multicenter and randomized clinical trials to determine the optimal approach to the treatment of recurrent HCV infection following OLT. Most published studies were small, lacked controls, had short follow-up periods, and were devoid of histologic analysis. Furthermore, most of the published studies are largely incomparable due to differences in the definition of recurrent hepatitis C, timing of anti-HCV therapy administration relative to transplantation, the drugs and doses used and regimens employed, and the study end points assessed (i. e. biochemical, virologic and histologic end points have not all been consistently investigated). In lieu of large studies in post-transplant patients, monotherapy with conventional interferon or monotherapy with pegylated interferon should be considered in recipients with histologically confirmed recurrence of HCV infection. The role of hepatitis C immunoglobulin and new imunosuppression agents in the management of post-transplant HCV infection is still evolving.     

Transplant-associated autoimmune mechanisms in human hepatitis C virus infection

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The AMLR of noninfected laboratory volunteers could be amplified by preincubating their stimulating cells (APCs) with enriched HCV possibly in immune complex (pHCV-IC). This amplification appeared only with specific combinations of HCV strains with HLA DR serotypes. In addition, HCV-primed T cells could be generated to the virus which displayed accelerated activation kinetics. Liver infiltrating lymphocytes extracted from HCV-positive end-stage diseased livers had significantly higher proliferative and cytotoxic reactivity to autologous (HCV-infected) hepatocytes than the extracted lymphocytes responding to autologous hepatocytes from HCV-negative livers. These findings offer evidence of dynamic autoimmune mechanisms in the spectrum of progression of HCV disease and may help to predict the effect of intervention at various intervals in this progression in organ transplant recipients.     

Management of viral hepatitis in liver transplant recipients

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.     

Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation

Chronic infection with the hepatitis C virus (HCV) represents one of the major causes for end-stage liver disease worldwide. Although liver transplantation offers an effective treatment, HCV reinfection of the transplanted graft is a critical and almost inevitable complication with major influence on graft- and patient survival. Pre-transplant antiviral therapy in advanced liver disease is limited by poor tolerance and only applicable to mildly decompensated patients but was able to show promising results in patients reaching negative viral load when undergoing transplantation. Prophylactic therapy with HCV antibodies during the anhepatic phase has not been shown to be effective in studies to date. Antiviral therapy after transplantation but before evidence of reinfection, so called pre-emptive treatment, is limited by frequent complications and a high rate of side effects. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic Hepatitis C. With a combination therapy of pegylated interferon and ribavirin, sustained virologic response rates of 25–45% are achieved. However, tolerability is often poor, and the need of dose reduction is frequent. To date, there is no general consensus on modality, timing and dosing of antiviral treatment of HCV in patients with advanced liver disease and after liver transplantation. More randomised, controlled trials are needed. Moreover, upcoming new treatment approaches, e.g. specifically targeted antiviral therapy for hepatitis C (STAT-C) with HCV-specific polymerase and protease inhibitors, may represent a therapeutic alternative.     

Hepatitis C therapy with long term remission after renal transplantation

Hepatitis C virus infection (HCV) is common in patients with end-stage renal disease (ESRD) and long observation periods have shown the detrimental effect of HCV infection on patient and graft survival after renal transplantation. At present, interferon is the most important agent for the treatment of hepatitis C in ESRD; however, limited information exists concerning the long-term response of patients who undergo renal transplantation after successful antiviral therapy. We describe the evolution of HCV infection in a dialysis patient with hepatitis C who was successfully treated with interferon alpha and then underwent renal transplantation. He received aggressive immunosuppression during the induction phase and for allograft rejection; however, regular screening showed complete absence of biochemical and virological relapse of HCV over a 6-year post-transplantation period. We conclude that interferon can offer excellent response in selected dialysis patients with hepatitis C. Alternative strategies with newer antiviral agents are currently under active investigation.     

The natural history of hepatitis C virus (HCV) infection

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. Although the incidence of hepatitis C infection has dramatically decreased during the past decade, the worldwide reservoir of chronically infected persons is estimated at 170 million, or 3% of the global population. There is much controversy surrounding the natural history of hepatitis C infection. The rate of chronic HCV infection is affected by a person's age, gender, race, and viral immune response. Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection, and are at risk for the development of extrahepatic manifestations, compensated and decompensated cirrhosis, and hepatocellular carcinoma (HCC). The rate of progression to cirrhosis is highly variable, and is influenced by several factors, including the amount of alcohol consumption, age of initial HCV infection, degree of inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid conditions. An estimated 10%-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk of developing HCC. An understanding of the natural history of hepatitis C is essential to effectively manage, treat, and counsel individuals with HCV infection.     

Hepatitis C virus recurrence and immunosuppression-free state after liver transplantation

HCV-related disease is the most common indication for liver transplantation (LT). HCV recurrence, which is almost universal, has a significant impact on patient and graft survival after LT and still represents a great unsolved issue for the liver transplant community. Several treatment strategies have been proposed. Since antiviral therapy has limited efficacy and can be administrated only in selected transplant recipients and additionally that immunosuppressive drugs have a negative impact on HCV re-infection, the achievement of an immunosuppression-free state after LT could play a central role in the avoidance of rapid HCV recurrence.     

Chronic liver diseases in patients with chronic kidney disease

The morphological and functional integrity of the liver is vital to human health in general as well as to patients with renal disease. Any chronic liver disease will eventually lead to liver insufficiency. Liver enzymes are routinely measured to assess liver function in patients with or without renal failure. The use of standard reference values of aminotransferases to help detect liver disease is less useful in patients on chronic dialysis therapy. Some investigators have suggested that, to increase the sensitivity of liver function tests among dialysis patients, lower "normal" values of aminotransferases should be adopted. Liver biopsy may be helpful for assessing the activity and severity of liver disease, especially in chronic viral liver diseases. The most widely used scores are Ishak (6-point scale) and METAVIR (4-point scale). The most important chronic liver diseases associated with chronic renal disease are hepatitis B and C. Several types of renal disease have been recognized: mixed cryoglobulinemia, membranoproliferative glomerulonephritis, membranous nephropathy and polyarteritis nodosa. In any patient first ever diagnosed with any of the mentioned features, serologic and molecular tests for hepatitis B and/or C should be done. There is limited information on the treatment of HBV-associated renal diseases. Nonrandomized studies suggest that antiviral therapy may be beneficial in patients with glomerular disease or vasculitis due to HBV. According to Croatian National Guidelines for Hepatitis B and C, treatment with antiviral drug is recommended for patients with chronic renal disease, especially those on the waiting list for kidney transplantation. Decision on the type and duration of treatment is based on the level of viremia and biochemical and histological activity of liver disease. Several antiviral drugs are currently used for hepatitis B: pegylated interferon alpha-2a and nucleot(z)id analogues. The choice of analogues is based on their genetic barrier and resistance. The probability to develop resistance is much higher in prolonged treatment, more than 1 year. To avoid it, regular check-ups are mandatory. First check-up is recommended after 12 weeks of treatment to detect the possible primary resistance to treatment. Similar approach is used in patients with hepatitis C. Today's standard of care is treatment with a combination of pegylated interferon alpha and ribavirin. Serum concentration of both drugs rises in patients with impaired renal function. The dosage should be corrected according to the glomerular filtration rate. Treatment with pegylated interferon alpha is not recommended in patients with glomerular filtration rate less than 15 mL/min and ribavirin less than 50 mL/min. Recent evidence suggest that nonalcoholic fatty liver disease is associated with an increased prevalence and incidence of chronic renal disease. Current treatment recommendations for nonalcoholic fatty liver disease are limited to weight reduction and treatment of any component of the metabolic syndrome. Liver cirrhosis is the terminal stage of any chronic liver disease. Mortality differs according to the stage of cirrhosis evaluated with Child-Turcotte-Pugh score. The worst prognosis have patients with grade C cirrhosis, which should be borne in mind when evaluating patients with terminal renal disease for treatment with kidney transplantation.     

Association of interleukin-18 polymorphisms and plasma level with the outcome of chronic HCV infection

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease throughout the world, and may progress to cirrhosis and hepatocellular carcinoma (HCC). Immunological factors, especially cytokines and some host genetic variations, rather than direct HCV action, seem to play an important role in the pathogenesis of HCV infection. Elevated levels of interleukin-18 (IL-18) were described previously for chronically (HCV)-infected patients. This study is aimed at investigating IL-18 promoter polymorphisms (-607C/A and -137G/C) in HCV-infected patients with different disease severities (chronic hepatitis C, liver cirrhosis and HCC) and establishing an association between these polymorphisms and IL-18 plasma concentration with the outcome of chronic HCV infection. The carriage of at least one C allele at position -607 (CC + CA) was associated with a higher risk of cirrhosis and HCC (P = 0.032). Compared with controls, HCV-infected patients had significantly higher levels of IL-18 (P = 0.0001) that correlate with disease severity (P = 0.01, P = 0.001, P = 0.0006, respectively). In conclusion, we supposed a possible implication of IL-18 promoter polymorphisms in the pathogenesis of chronic HCV infection.     

Chronic kidney disease after liver transplantation: Recent evidence

Chronic kidney disease is a common complication after liver transplantation with an incidence ranging between 20% and 80%. Studies of renal function after liver transplantation have yielded conflicting results: the wide range in incidence rates of chronic kidney disease (CKD) following liver transplantation is related to the methods for measuring kidney function, and various criteria for defining renal dysfunction, among others. An important cause of CKD among liver transplant recipients is calcineurin inhibitor-based immunosuppression. Additional predictors of CKD post-liver transplantation include pre-transplant kidney function, peri-operative acute kidney failure, age, and hepatitis C. A recent meta-analysis of observational studies revealed that, in the subgroup of studies provided with glomerular filtration rate at baseline, the summary estimate of relative risk and 95% confidence intervals (CI) for developing chronic renal failure among liver transplant recipients with diminished renal function at transplant was 2.12 (95% CI, 1.01-4.46, p=0.047). Acute renal insufficiency is common immediately after liver transplantation, whereas the course of CKD after liver transplantation appears progressive over time. Only preliminary information exists on kidney pathological findings in recipients of liver transplants with CKD. Introduction of the Model for End-stage Liver Disease for the allocation of liver grafts has not increased the occurrence of renal dysfunction following liver transplantation. Chronic kidney disease following liver transplantation increases cardiovascular burden dramatically. The use of mycophenolic acid- or sirolimus-based immunosuppression in calcineurin-inhibitors sparing protocols is an area of intense research.     

Combination therapy with ribavirin and amantadine in renal transplant patients with chronic hepatitis C virus infection is not superior to ribavirin alone.

BACKGROUND: Standard treatment of chronic hepatitis C virus (HCV) infection based on interferon is not an option in renal transplant recipients due to the high risk of acute allograft rejection. OBJECTIVES: To assess efficacy and tolerability of combined treatment with ribavirin and amantadine regarding viral clearance, normalization of liver enzymes, and improvement of HCV-related hepatopathy and graft nephropathy in HCV-RNA-positive renal transplant patients. STUDY DESIGN: Prospective randomized controlled study comparing ribavirin, 1000 mg daily (n=7), versus ribavirin, 1000 mg, in combination with amantadine, 200 mg daily (n=8), for 12 months, versus no therapy (controls, n=26). Results were evaluated by intention-to-treat analysis. RESULTS: No relevant differences among treatment groups were found regarding liver enzymes, HCV viremia, liver histology and renal parameters. However, antiviral treatment was limited by anemia, resulting in premature withdrawal from therapy and requiring substitution with recombinant erythropoietin in most patients. The best predictor for tolerability of active treatment was a creatinine clearance rate>50 ml/min. CONCLUSIONS: Addition of amantadine to ribavirin seems not to be superior to ribavirin monotherapy in renal transplant patients with chronic replicating HCV infection. However, this may be explained in part by the poor tolerability of both ribavirin and amantadine in patients with impaired renal function, resulting in drop-outs and subtherapeutic drug dosage.     

Is replication of hepatitis C virus a marker of activity of infectious process? (Findings of polymerase chain reaction and morphological analysis of liver biopsy specimens)

Comparative study of replication markers of hepatitis C virus in various biological substrates and evaluation of activity of chronic HCV infection in liver biopsy specimens showed that replication of hepatitis C virus and the number of HCV-infected hepatocytes did not promote liver damage in chronic hepatitis C. These findings indicate that the expression of antiviral reactions by liver parenchyma cells plays the key role in the morphogenesis of HCV infection.     

Hepatitis C-associated granulomas after liver transplantation: morphologic spectrum and clinical implications

Liver granulomas have been described in biopsy specimens from people with de novo chronic hepatitis C virus (HCV) infection and in allograft biopsy specimens from recipients of transplants for HCV-related liver disease. The latter have not been well studied, and there are no data regarding the prevalence, morphologic spectrum, and clinical significance of HCV-associated granulomas after liver transplantation. We observed granulomas in allograft liver biopsy specimens of 4 (8%) of 53 recipients of transplants for HCV-related end-stage liver disease during a 3-year period. Initial appearance of granulomas ranged from 4 to 41 weeks after transplantation. Lobular and portal nonnecrotizing, epithelioid granulomas and lobular microgranulomas were observed, with the latter predominating. Serum transaminase and alkaline phosphatase levels were significantly higher in patients with granulomas than in age- and sex-matched control subjects, but histologic disease activity, cellular rejection scores, HCV genotypes, viral titers, and retransplantation rate owing to recurrent disease were not significantly different. Our study suggests that a granulomatous response to HCV infection occurs in a subset of patients after transplantation; however, this histologic finding does not portend a worse clinical outcome.     

环孢素治疗丙型肝炎病毒RNA阳性肾移植患者的抗病毒复制效应

背景：丙型肝炎病毒阳性患者接受肾脏移植后,免疫抑制剂的选择及抗丙型肝炎病毒药物的选用是目前关注的重点。 目的：探讨环孢素在丙型肝炎病毒RNA阳性肾移植患者中除抗排斥作用以外的抗病毒复制作用。 方法：纳入11例丙型肝炎病毒RNA阳性肾移植患者,于采用环孢素+咪唑立宾+泼 尼松治疗方案时记为入组,分别对入组前、入组后6,12个月时患者丙型肝炎病毒RNA、血红蛋白、肝肾功能等指标的变化进行检测。 结果与结论：入组前、入组6个月、入组12个月11例患者丙型肝炎病毒RNA中位数(copies/mL)分别为1.22×10⁷,1.11×10⁴,4.19×10⁶;入组6个月时,有8例患者丙型肝炎病毒RNA转阴(丙型肝炎病毒RNA<500 copies/mL),总应答率为73%(8/11);至随访结束,持续病毒学应答率为55%(6/11)。且入组治疗前后患者谷丙转氨酶、血清肌酐、血尿酸水平差异均无显著性意义(P > 0.05),患者血红蛋白水平在入组后升高。随访过程中,仅1例发生排斥反应,甲基强的松龙冲击治疗 3 d后好转。提示对于合并丙型肝炎的肾移植患者,选用环孢素为主的治疗方案,在达到抗排斥治疗作用的同时,可发挥抑制丙型肝炎病毒复制的作用。     

Apoptosis and hepatitis C virus infection in renal transplant recipients

Hepatocellular injury in renal transplant recipients with hepatitis C virus (HCV) infection remains unclear. The suppressed immune response, in combination with increased viremia levels, provides a unique setting for the study of a potential HCV-induced apoptotic process.Liver biopsy specimens from 59 HCV-infected renal transplant recipients were examined histologically. DNA fragmentation was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling assay, and the CD8 T-cell count was assessed immunohistochemically.A low apoptotic index (0-2.5) was observed in 31 cases, a moderate index (2.6-5) in 16, and a high index (>5) in 12. Apoptotic cell death correlated significantly with viremia because it was demonstrated by higher HCV-RNA levels in cases with a high number of apoptotic cells (odds ratio, 2.96; 95% confidence interval, 1.0-8.5; P = .04). No correlation was found between the apoptotic index and hepatitis necroinflammatory activity, CD8 cell count, fibrosis stage, immunosuppressive therapy, or genotype.In HCV-infected renal transplant recipients, apoptotic cell death seems to be associated with high viral load, thus providing indications of viral interference in the pathogenetic process.     

Hepatitis C virus replicates in sweat glands and is released into sweat in patients with chronic hepatitis C

Hepatitis C virus (HCV) replicates in salivary glands of chronic hepatitis C patients and is released into the saliva, suggesting that HCV may replicate in other exocrine glands. The presence of positive and negative HCV RNA strands was demonstrated by in situ hybridization, and of HCV core protein by immunohistochemistry, in sweat glands and keratinocytes in healthy skin biopsies from 15 patients with chronic hepatitis C and 10 anti-HCV negative patients with chronic liver disease. Positive and negative HCV RNA strands were detected in 9.6 +/- 5.2% and 4.2 +/- 3.8%, respectively, of the epithelial cells of eccrine sweat glands. Core protein was detected in 6.0 +/- 3.93% of these cells. HCV RNA resistant to RNase digestion (encapsidated HCV RNA) was detected in 10/10 sweat samples from HCV-infected patients. Positive and negative HCV RNA strands were detected in 6.7 +/- 2.97% and 3.0 +/- 3.08% of the keratinocytes, respectively. HCV core protein was found in 4.5 +/- 2.76% of these cells. No HCV RNA or HCV core protein was detected in the skin biopsies from the 10 anti-HCV negative patients. In conclusion, HCV replicates in eccrine sweat glands cells and keratinocytes in healthy skin and is released into the sweat.     

Unexpected distribution of hepatitis C virus genotypes in patients on hemodialysis and kidney transplant recipients

The distribution of hepatitis C virus (HCV) genotypes in patients on hemodialysis and in kidney transplant recipients was compared with that observed in a control group composed of HCV-infected individuals from the general population. A total of 340 patients were included in the study: 46 with end-stage renal disease on regular hemodialysis treatment, 22 kidney transplant recipients and 272 controls matched for sex and age at a 4:1 ratio (controls to patient). HCV genotype was determined by sequencing of the 5' untranslated region of the HCV genome. No difference was observed in the distribution of HCV genotypes in hemodialysis patients and renal transplant patients (P = 0.47). However, when each of these groups was compared with the control group, a significant difference was detected in the genotype distribution (P < 0.001). In hemodialysis and renal transplant patients the most prevalent subtype was 1a, followed by 1b, 3, and other less prevalent genotypes (2, 4, and 5), whereas in the control group the most prevalent subtype was 1b, followed by 3, 1a, and others. That observation may reflect differences in the epidemiology of HCV infection, viral characteristics and host factors in renal patients in comparison to the control group.     

Donor-specific hyporesponsiveness in ELISPOT assay is associated with early recurrence of hepatitis C in liver transplant recipients

Recurrence of hepatitis C in liver transplant recipients is a common event that often leads to loss of the allograft. There are no means to prevent, or even predict, those patients who are more prone to early aggressive recurrence. Therefore there is an increased need for tailored immunosuppression protocols specific to this patient population. Fifteen liver transplant recipients (eight hepatitis C virus [HCV]+; 7 HCV-) were followed for 12-24 months after transplantation. The frequency of donor-specific interferon (IFN)-gamma- or interleukin-10-producing lymphocytes was monitored using ELISPOT assays. Of the eight HCV+ recipients, six experienced recurrence within the first year after transplant. All six patients had very low (negligible) frequency of donor-specific IFN-gamma precursors; in most cases not higher than the nonstimulated (spontaneous) secretion rate. The other two patients who did not recur exhibited donor-specific IFN-gamma reactivity. A significant difference in the frequency of alloantigen-specific T cells was observed between HCV+ recipients and patients with other indications for transplantation. The results of this preliminary study suggest that posttransplant monitoring of the frequency of donor-specific IFN-gamma-producing precursors may differentiate a subset of patients at risk for early recurrent hepatitis C and therefore may help to devise treatment strategies for HCV+ liver recipient after transplantation.