Detection of antibody to hepatitis C virus in renal transplant recipients.

Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors retrieved in the same interval for serologic evidence of hepatitis C viral (HCV) infection using the enzyme-linked assay for anti-HCV antibody. Of 596 HBsAg negative patients, 180 (30%) were anti-HCV positive at the time of transplant. One-year posttransplant, 117 (22%) had detectable levels of anti-HCV antibody. Chemically significant hepatitis developed in 52/234 (22%) anti-HCV positive patients, and 26 of these followed a clinical course consistent with chronic hepatitis. Significantly more males and patients with antibody to HCV detectable at 1 year posttransplant were in the group experiencing an increase in liver enzymes. Ten-year patient and graft survival was 78% and 50%, respectively, for the anti-HCV positive patients who had an elevation of alanine aminotransferase, and 76% and 57% for the cohort maintaining normal liver function (P = NS). There were also no differences in patient and graft survival among the anti-HCV positive group and the consistently sero-negative patients. Of 484 cadaver organ donors with serum available for analysis (out of 1200 retrieved), 67 (14%) were anti-HCV positive at the time of organ donation. Among 23 anti-HCV negative kidney recipients who received a kidney from an HCV antibody positive donor, only one had seroconverted at 1 year posttransplant. Antibody to HCV appears to be widespread among renal transplant recipients and cadaver organ donors. We were unable to demonstrate any evidence of long-term adverse effects on patient and graft survival among anti-HCV positive patients employing the first generation anti-HCV assay.     

Hepatitis C in liver transplant patients

Abstract The aim of this study was to determine whether infection by the hepatitis C virus (HCV) recurs after orthotopic liver transplantation (OLT) and to define the natural history of post-transplantation chronic hepatitis due to HCV. Of 70 patients, 10 (14.3 %) were found to have antibodies to HCV before transplantation. After OLT 14 of the 70 patients (20%) had positive anti-HCV antibodies: 8 of 10 positive pre-OLT (80%) and 6 of 60 negative pre-OLT (10%). Of 14 patients anti-HCV + post-OLT (57%), developed 8 chronic hepatitis: chronic persistent hepatitis in three patients, chronic lobular hepatitis in three patients and chronic, active hepatitis in two patients. We treated four patients with interferon obtaining normalization of transaminases in three of them after 6 months, but with a severe relapse in two. These results suggest that hepatitis C recurs in a majority, of liver transplant recipients and that morbidity is an important consideration. Interferon treatment of these patients requires further study to obtain conclusive results.     

肾移植供者丙型肝炎病毒(HCV)感染状况及移植抗HCV阳性供肾对受者的影响

目的了解肾移植供者丙型肝炎病毒(HCV)的感染率及移植抗HCV阳性供肾对受者的影响.方法采用酶联免疫吸附(ELISA)法检测肾移植供、受者的抗HCV;巢式多聚酶链反应(Nest-PCR)法检测HCVRNA;根据供、受者HCV状态将受者分为4组,对各组受者进行1年以上的随访研究.结果(1)供者HCV的感染率为4.35%;(2)抗HCV阴性的受者,接受抗HCV阳性供肾移植后,有62.5%的抗HCV及HCVRNA转为阳性,术后丙氨酸转氨酶(ALT)水平和肝功能损害发生率明显高于无HCV感染组;(3)将抗HCV阳性的供肾移植给抗HCV阳性的受者,与抗HCV阴性的受者接受抗HCV阳性供肾移植以及与抗HCV阳性的受者接受抗HCV阴性供肾的临床效果相同.结论(1)移植抗HCV阳性供肾能传播HCV,可影响受者的肝脏病变,但这种影响程度较轻;(2)将抗HCV阳性供肾移植给抗HCV阳性的受者,既不增加传播HCV的危险性,又能扩大供肾来源,是解决我国供肾短缺的一项值得考虑的策略.     

维持性血液透析患者感染乙型和丙型肝炎的分析

目的为了评价血液透析（血透）患者乙型和丙型肝炎（HBV、HCV）感染状态及对临床情况和肝功能的影响。方法对62例血透患者应用ELISA法和RT-PCR法检测抗-HCV和HCVRNA，采用斑点杂交法和固相放免法检测HBV标志，并检测肝功能和血浆蛋白电泳。结果62例患者中，抗-HCVIgM阳性27例（43．6％），抗-HCVIgG阳性29例（46．8％），HCVRNA阳性34例（54．8％），三项任一项阳性37例（59．7％），5例（8．1％）HBsAg阳性，其中HBeAg和HBVDNA阳性3例。结论向透患者中HCV感染严重，临床情况及预后差，检测血浆蛋白和电泳较肝功能酶学能更好地作为肝炎诊断和反映病情的指标。     

The clinical outcome of hepatitis C virus antibody-positive renal allograft recipients.

In order to investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in renal transplant patients, the evolution of anti-HCV status, and clinical outcome in anti-HCV-positive renal allograft recipients, we tested the sera from 120 renal transplant patients for anti-HCV. Thirty-eight patients were hepatitis B surface antigen (HBsAg)-positive. Two patients were anti-delta-positive. A total of 79 patients (65.8%) had at least one serum positive for anti-HCV. Anti-HCV positivity decreased after transplantation for more than 5 years (65.5% at transplantation versus 37.9%, 78.3 +/- 13.4 months later). Among those with positive anti-HCV, the HBsAg-positive group had significantly higher incidence of chronic hepatitis (50% vs. 25.5%, P = 0.026) and liver cirrhosis (21.4% vs. 0%, P = 0.001) than HBsAg-negative group. Among the 82 HBsAg-negative patients, the prevalence of anti-HCV was significantly higher in those with chronic hepatitis than in those without (86.7% vs. 56.7%, P = 0.027). We conclude from this study: (1) anti-HCV positivity is quite prevalent in renal transplant patients; (2) coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may lead to aggressive liver disease and cirrhosis; HCV infection alone has a more benign clinical outcome; and (3) HCV infection is an important cause of posttransplant chronic hepatitis in HBsAg-negative patients.     

Incidence and outcome of hepatitis C virus infection after liver transplantation

Abstract The objective of this study was to determine the incidence and outcome of hepatitis C virus (HCV) infection after liver transplantation (OLT). Fifty-two transplanted patients were studied. Serum samples were examined for antibodies to HCV (anti-HCV) and HCV-RNA by PCR, before and after OLT. Patients were distributed into two groups: group 1 consisted of 24 patients (pretransplant anti-HCV positive) and group 2 consisted of 28 patients (pretransplant anti-HCV negative). One year after OLT, HCV-infected patients were evaluated by liver biopsy. HCV-RNA was detected in 28 of the 52 (53.9%) patients after OLT. Twenty-two patients in group 1 (96%) were reinfected. In group 2, acquired HCV infection was detected in six (21.4%) patients. At 6 and 12 months, one and five of six patients had seroconverted, respectively. Liver biopsy in 23 HCV-infected patients showed chronic hepatitis in 18 (78%) cases (2, chronic persistent hepatitis; 3, chronic lobular hepatitis and 13, chronic active hepatitis). Fourteen of the 23 (60.8 %) patients were asymptomatic. Most symptomatic patients had chronic hepatitis with cholestasis. Overall, 18 of 20 cases of chronic hepatitis diagnosed in OLT recipients were HCV related. Mortality beyond 6 months after OLT was slightly higher in the HCV-infected group ( P = 0.055). In conclusion, HCV reinfection is almost universal. Acquired HCV infection post-OLT is frequent. HCV-infected patients frequently develop chronic hepatitis. Most chronic hepatitis after transplantation are HCV related.     

Allograft transmission of hepatitis C virus infection from infected donors in cardiac transplantation

BACKGROUND: The frequency and outcome of hepatitis C virus (HCV) infection in recipients of hearts from HCV-infected donors remains poorly characterized. METHODS: Between 1991 and 1999, 10 anti-HCV-negative patients received hearts from donors who were anti-HCV and HCV RNA-positive. Each recipient was tested for anti-HCV and HCV RNA and serially evaluated for liver dysfunction. Recipient records were reviewed for cumulative steroid boluses in the first posttransplant year and other components of the immune suppression regimen. We analyzed recipient outcome in relation to the virologic status of the donor, including the level of HCV RNA and genotype and the type of antirejection therapy. RESULTS: All 10 recipients became HCV RNA positive. Donor-recipient pairs expressed identical genotypes in each instance. Six of nine evaluable recipients developed biochemical evidence of hepatitis. Recipients with genotype 1 (1a, 1b) accounted for five of the six cases, and all patients with genotype 1 developed hepatitis. Severe liver injury occurred in two patients. Two deaths occurred, both of which were genotype 1 patients who had been given multiple boluses of corticosteroids in the first posttransplant year. No definite relationship between viral load in the donor and recipient outcome was found. CONCLUSION: Transmission of HCV infection from cardiac donors who are viremic at the time of organ donation occurs with high frequency and can cause severe hepatitis. Hearts from infected patients should probably be restricted to those recipients who already have evidence for hepatitis C or are in need of emergent transplantation.     

肾移植患者丙型肝炎病毒感染的研究

目的 了解肾移植患者ＨＣＶ感染情况及感染对临床影响。方法 对６７例肾移植患者进行至少１年的随访,用第二代酶联免疫吸附法（第二代ＥＬＩＳＡ法）和巢式多聚酶链反应（Ｎｅｓｔ－ＰＣＲ法）测定血清中丙型肝炎病毒抗体（抗ＨＣＶ）和丙型肝炎病毒核糖核酸（ＨＣＶＲＮＡ）,免疫组化链霉亲合 酶联法（ＬＳＡＢ法）测定丙型肝炎病毒非结构区３区、５区基因表达的抗原（ＨＣＶ－ＮＳ３、ＮＳ５抗原）。结果 抗ＨＣＶ阳性率５０     

Risk of liver disease in HCV-seropositive kidney transplant recipients.

OBJECTIVE: This study determined whether renal allograft recipients with antibodies to hepatitis C virus (HCV) at the time of transplantation experienced increased morbidity or mortality from hepatitis, liver disease, or hepatocellular carcinoma compared with patients without anti-HCV. SUMMARY BACKGROUND DATA: Chronic liver disease is a cause of significant morbidity and mortality after kidney transplantation and the contribution of HCV to this problem has not been determined. The recent characterization of the HCV genome has resulted in the development of screening tests for antibody to HCV, allowing the identification of end-stage renal disease patients with anti-HCV who are candidates for transplantation. The risk to these patients for the development of hepatic complications after subsequent transplantation is unknown. METHODS: Archived sera obtained from 163 kidney transplant recipients at the time of transplantation were tested for anti-HCV using the Abbott HCV 2.0 second-generation test system. Sera containing anti-HCV were further analyzed for reactivity against specific HCV recombinant proteins, including core, NS3 (c33c), and NS4 (c100-3), to determine whether a pattern could be identified in patients with hepatic complications. The follow-up of all patients was current (mean length of follow-up was 33 months) to identify patients with hepatic complications. All patients had previously been tested for HBSAg. RESULTS: Twenty-nine patients (18%) had anti-HCV and three (1.8%) had HBSAg. Forty-five patients (28% of total) had transient elevations of AST or ALT without subsequent evidence of liver disease. Three patients had a syndrome of acute hepatitis. Chronic liver disease developed in only six patients (3.6%) after transplantation. Four had anti-HCV only, one had HBSAg only, and one was positive for both. However, of the 29 patients with anti-HCV, chronic liver disease developed in 5 (17%), including 1 patient who was positive for HBSAg. No patient had hepatocellular carcinoma. CONCLUSIONS: Perturbations of liver function were common in the kidney transplant recipients studied, most were self-limited, and few were associated with evidence of viral hepatitis. The risk of developing     

Seroprevalence and outcome of hepatitis C in liver transplantation

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immuno-suppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1–5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.     

Hepatitis C virus infection among kidney transplant recipients.

The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 +/- 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis and to the amount of blood transfusions. Following transplantation, nine (28%) seropositive patients lost anti-HCV and five (14%), previously seronegative, seroconverted. Anti-HCV was found to be positive in 92% of the patients with chronic liver disease who were on hemodialysis, but in 56% in kidney recipients with chronic hepatitis. Anti-HCV was positive in 50% of patients with resolving hepatitis before transplantation, but only in 21% of those with acute hepatitis following transplantation. This study confirms the high risk of HCV infection among hemodialysis and kidney recipient populations, and also that HCV is closely related with the length of time the patient is on hemodialysis as well as the number of blood units transfused. HCV is the main cause of acute and chronic liver disease in hemodialysis patients and of chronic liver disease in kidney recipients, but does not clearly influence the survival of the allograft nor that of patients.     

Chronic liver disease in kidney recipients with hepatitis C virus infection

BACKGROUND: The prevalence of anti-hepatitis C virus (HCV) positive test is higher among patients in dialysis and in kidney recipients than in general population. Hepatitis C virus infection is the main cause of chronic liver disease in renal transplant patients. Liver biopsy and virological analysis were performed to clarify the grade of liver damage in kidney recipients. METHODS: Renal recipients patients with at least 5 yr under immunosuppression were submitted to clinical and laboratory analysis. Patients who tested anti-HCV positive were candidates to liver biopsy with no regard to transaminase levels. RESULTS: Forty-five patients tested anti-HCV positive and 42 anti-HCV negative. Twenty-six anti-HCV and RNA-HCV positive patients were submitted to liver biopsy. Seventy-three percentage of these patients presented chronic active hepatitis, from these only one patient presented cirrhosis. Only 29% of the anti-HCV positive group presented elevated alanine aminotransferase levels. Anti-HCV positive patients presented longer previous time on dialysis and less rejection episodes than the group anti-HCV negative (p < 0.05). All anti-HCV positive patients but one tested RNA-HCV positive by polymerase chain reaction (PCR). CONCLUSIONS: In this series the prevalence of anti-HCV positive is 51.7%. Most of the patients presented liver damage in histology caused by HCV. However, we found only mild or minimal fibrosis and inflammatory activity grade, despite 10 yr of HCV infection and 5 yr of immunosuppressive treatment. Only one patient presented cirrhosis (4%). Performing serial liver biopsies in a long-term follow-up is needed to clarify the impact of HCV infection in renal transplant patients.     

Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation

BACKGROUND: Initial studies utilizing interferon-alpha and ribavirin for the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation showed promising results. Here we report our single-center experience using this combination therapy. METHODS: Liver transplant recipients with recurrent HCV (elevated serum aminotransferases, positive serum HCV RNA, and biopsy-proven hepatitis without rejection) received interferon-alpha (1.5-3 million units subcutaneously three times a week) and ribavirin (400-1000 mg p.o. daily) for 12 months or more. Serum aminotransferases, HCV RNA, and severity of hepatitis were followed. RESULTS: Thirty-two patients have been treated for at least 3 months, including 13 who have been on 12 or more months of therapy. Three died from allograft failure due to recurrent HCV. Dose reductions of interferon-alpha and/or ribavirin occurred in 22 patients. Thirteen had their medications permanently discontinued for severe adverse effects. Twenty-six patients (81%) had a biochemical response (BR; normalization of serum aminotransferases) after 3 months. End-of-treatment and sustained BR were 77% and 71%, respectively. Mean viral loads decreased 68-77%; however, only three patients became serum HCV RNA negative. After 12 months of therapy, no histological improvement was observed in 11 patients who were biopsied. Patients who received mycophenolate mofetil or daclizumab had a less likelihood of achieving a BR. CONCLUSIONS: A significant number of patients did not tolerate interferon-alpha or ribavirin. Although BR was excellent and mean viral loads decreased significantly, virological clearance was poor and no histological improvement was noted. A more efficacious treatment with less adverse effects for recurrent HCV after liver transplantation is needed.     

乙型肝炎病毒和丙型肝炎病毒感染对肾移植受者长期存活的影响

对乙型肝炎病毒表面抗原阳性与丙型肝炎病毒抗体阳性的肾移植患者慢性肝脏疾病的发病情况进行研究，以探讨肝炎病毒感染对肾移植患者的患乾。结果表明，ＨＢｓＡｇ阳性或ＨＣＶ抗体阳性患者慢性直脏疾病的发病率明显高于阴性患者，但其对人／肾１年存活率的影响不显著；     

Leukopenia and thrombocytopenia in hemodialysis patients with hepatitis B or C virus infection and non-hemodialysis patients with hepatitis cirrhosis

AIMS: To investigate the relation of leukopenia and thrombocytopenia in hemodialysis (HD) patients with hepatitis C virus (HCV) infection. MATERIALS AND METHODS: The study included 86 HD patients with hepatitis B surface antigen-negative and hepatitis C antibody-negative, 28 HD patients with hepatitis C antibody-positive, 22 HD patients with hepatitis B surface antigen-positive, 78 non-HD patients with hepatitis B-induced liver cirrhosis and 38 non-hemodialysis patients with hepatitis C-induced liver cirrhosis. The following parameters were checked: anti-HCV, hepatitis B surface antigen, hemoglobin, hematocrit, white blood cells, platelets, calcium, phosphate, iron, ferritin, albumin, globulin, aspartate transaminase (AST), alanine transaminase (ALT) and C-reactive protein. The history of blood transfusions, medications, erythropoietin doses and adequate dialysis (KTNV) for 6 consecutive months was also recorded from charts. RESULTS: The HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced liver cirrhosis had higher prevalences of leukopenia (39.3%, 43.6% and 50% vs. 15.1%; p < 0.001) and thrombocytopenia (67.9%, 89.7% and 81.6% vs. 34.9%: p < 0.001) than HD patients with serum anti-HCV(-)HbsAg(-). The WBC (4,432 +/- 1,394, 4,792 +/- 2,263 and 4,624 2,446 vs. 5,590 +/- 1,500/mm3; p < 0.001) and platelet counts (140 +/- 45, 80 +/- 50 and 89 +/- 65 vs. 186 +/- 62 x 10(3)/mm3; p < 0.001) of HD patients with positive serum anti-HCV and non-HD patients with hepatitis B- or C-induced cirrhosis were also lower than HD patients without anti-HCV antibody. The liver cirrhosis patients had more thrombocytopenia than the HD patients with anti-HCV(+). The WBC and platelet counts did not vary between HD patients with HbsAg(+) and HD patients with anti-HCV(-)HBsAg(-). The durations of HD, hepatitis and liver cirrhosis were not related to the leukopenia or thrombocytopenia (p > 0.05). CONCLUSIONS: HCV infection associated with leukopenia and/or thrombocytopenia in HD patients is as common as in non-HD patients with liver cirrhosis. This may be due to the direct effect of hemopoiesis rather than the hyperspleenism of liver cirrhosis patients. There is a need for further prospective investigation to ascertain the clinical significance of leukopenia and thrombocytopenia in HD patients with anti-HCV(+). The prevalence of leukopenia and thrombocytopenia was higher in HD patients with hepatitis C than in HD patients with hepatitis B and HD patient without hepatitis.     

Infection of hepatitis C virus in patients with chronic renal failure undergoing hemodialysis therapy and staff members]

The prevalence of antibody to hepatitis C virus (anti-HCV) was determined in 564 patients and 145 staff members of nine hemodialysis (HD) units in Nagano Prefecture using an enzyme-linked immunosorbent assay based on the C 100 HCV antigen (the first generation anti-HCV assay). And also serum HBV markers were tested in these subjects. One hundred patients (18%) were anti-C100 HCV positive, indicating that this figure represents a much higher prevalence than that (0.9%) among general population in the same geographical area. Out of 141 patients without history of blood transfusion, 17 (12%) were positive for anti-C 100 HCV, suggesting that blood-transfusions-unrelated acquisition of HCV infection can occur. Anti-HCV prevalence correlated with both the blood units transfused and the duration of HD treatment. There was a significant difference in the prevalence of anti-C 100 HCV in individual dialysis units ranging from 0% to 53%. In the dialysis unit with prevalence of 53%, approximately half of the anti-HCV positive patients were found to have chronic liver disease. The prevalence of hepatitis B virus (HBV) markers among HD patients, on the other hand, was 36% (202/564). Fifty one (51%) of 100 anti-C 100 HCV positive patients and 151 (33%) of 464 anti-C 100 HCV negative patients were positive for HBV markers, with significant difference in HBV infection rate between the 2 groups. The prevalence of chronic liver disease, defined as abnormal serum transaminase levels for more than 6 months was significantly higher in anti-HCV positive patients than in anti-HCV negative ones (39% vs 10%, p less than 0.05), suggesting that HCV infection may contribute to chronic liver disease in HD patients. Among 145 staff members, only 3 (2%) were positive for anti-HCV, whereas 25 (17%) were positive for hepatitis B core antibody (anti-HBc), indicating prior HBV infection. With applying the second generation anti-HCV assay, which can detect antibodies to both capsid and nonstructural products of HCV gene, anti-HCV prevalence increased by two times in HD patients, but didn't change in HD staff members.(ABSTRACT TRUNCATED AT 400 WORDS)     

Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis C virus infection.

Fibrosing cholestatic hepatitis (FCH) has been described as a specific manifestation of hepatitis B virus (HBV) infection in liver allograft recipients characterized by a rapid progression to liver failure. Only sporadic cases have been reported in other immunocompromised groups infected with HBV and in a few transplant recipients with hepatitis C virus (HCV) infection. We present the occurrence of FCH in 4 HCV-infected renal transplant recipients within a series of 73 renal transplant recipients with HCV infection followed up closely serologically and with consecutive liver biopsies. All 4 patients received the triple-immunosuppressive regimen (azathioprine, cyclosporine A, methylprednisolone). The interval from transplantation to the appearance of liver dysfunction was 1 to 4 months and to histological diagnosis, 3 to 11 months. The biochemical profile was analogous to a progressive cholestatic syndrome in 3 patients, whereas the fourth patient had only slightly increased alanine aminotransferase and gamma-glutamyl transferase (gammaGT) levels. Liver histological examination showed the characteristic pattern of FCH in 2 patients, whereas the other 2 patients had changes compatible with an early stage. All patients were anti-HCV negative at the time of transplantation, whereas 2 patients, 1 with incomplete and 1with complete histological FCH features, seroconverted after 3 and 31 months, respectively. The patients were HCV RNA positive at the time of the first liver biopsy and showed high serum HCV RNA levels (14 to 58 x 10(6) Eq/mL, branched DNA). HCV genotype was 1b in 3 patients and 3a in 1 patient. After histological diagnosis, immunosuppression was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months posttransplantation, whereas the seroconverted patients showed marked improvement of their liver disease, which was histologically verified in 1 patient. In conclusion, FCH can occur in HCV-infected renal transplant recipients. It seems to develop as a complication of a recent HCV infection during the period of maximal immunosuppression and is associated with high HCV viremia levels. There are indications that drastic reduction of immunosuppression may have a beneficial effect on the outcome of the disease.     

Hepatitis C-positive Donors in Heart Transplantation

Hepatitis C virus (HCV) can be transmitted to heart transplant recipients by donor organs. Mid-term results were reported using HCV-positive donors in patients at risk of imminent death (group I, n = 10), or in patients who otherwise would not have been offered heart transplantation (group II, n = 10) because of age (9/10) or associated medical risk (1/10). Medical records pertaining to patients receiving HCV-positive allografts between July 1994 and December 1999 were reviewed. The recipients consisted of 19 males and one female, with a median age of 54 years for group I and 66 for group II. The HCV RNA level, seroconversion of anti-HCV antibody, biochemical liver dysfunction, and causes of death were examined. Older recipients received reduced immunosuppression. Two patients in group II were HCV positive and were also retransplants. The hospital mortality rate was 10% in group I and 20% in group II; both hepatitis C-positive recipients died postoperatively prior to discharge. All predischarge deaths were related to multi-system organ failure (MSOF). All 17 survivors were HCV negative prior to transplant. Of these, 4/17 seroconverted. HCV RNA was detected in two of them. At a median follow-up of 26.4 months, 2/11 current survivors continue to test anti-HCV positive and are RNA negative. Three-year actual survival was 40% for group I and 70% in group II. Transplant coronary artery disease (TCAD) accounted for one postoperative death in group I. Current data show that four out of 11 survivors had developed TCAD at 3-year follow-up, yielding an actual freedom from TCAD rate of 12/17 (70%) at 3-year follow-up. Hepatitis C transmission using a donor heart as the reservoir is moderate (25%). Limited use of such donors is justified in selected patients. The risk for hepatic disease may be reduced by tailoring immunosuppression specifically for such recipients, particularly if they are at low risk of rejection. Further studies are necessary to define a possible association between HCV and TCAD.     

Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss

BACKGROUND: The optimal immunosuppressive regimen for HCV-positive liver transplant recipients has not been established. Treatment for acute cellular rejection (ACR) with steroids is associated with increased viral replication and graft hepatitis. We retrospectively analyzed 232 patients after orthotopic liver transplantation (OLT) for HCV cirrhosis to determine the influence of methylprednisolone pulse therapy on long-term outcome after OLT. METHODS: Two hundred thirty-two liver transplants were performed in HCV-positive recipients between 1989 and 2001. Median follow-up was 4.4 years and median age of patients was 53 years (range 15 to 72 years). Immunosuppression consisted of tacrolimus (Tac) or cyclosporine (CyA) in different protocols. All rejection episodes were histologically proven. RESULTS: Twenty-eight of 232 (12.06%) graft losses were due to severe hepatitis C reinfection. Of 232 patients, 105 showed a minimum of one episode of ACR (45.25%). Of 232 patients, 71 (30.6%) received methylprednisolone pulse therapy once and 15 of 232 required OKT3 treatment for steroid-resistant rejection (6.4%). Of 232 patients, 19 (8.1%) required repeated steroid pulse therapy due to more than one episode of ACR. In patients with more than one episode of ACR, the risk of HCV-related graft loss was significantly enhanced (6/19, P < .05). The primary immunosuppression had no influence on the outcome in our data. CONCLUSION: Our data show that outcome of HCV-positive patients who require repeated steroid pulse therapy (RSPT) for ACR is significant worse than that in patients with a single pulse therapy. Therefore RSPT should be avoided in HCV-positive transplant recipients. New strategies to manage acute rejection are required for these patients.