Serial measurements of serum transaminases in renal transplant recipients with chronic hepatitis C: do they reflect disease severity?

Chronic hepatitis C infection is a common problem in renal allograft recipients, this study was designed to investigate the association of serum aminotransferase levels with liver histology, in renal transplant patients with chronic hepatitis C virus (HCV) infection, in the long term. METHODS: In this study, 82 HCV-infected renal allograft recipients, who were followed up with functioning grafts for at least 6 months, were analyzed. Patients were classified according to their transaminase values as persistently normal, intermittently abnormal, or continuously abnormal liver function tests. Serum transaminase levels exceeding at least 1.5 times the upper limit of normal (40 IU) for periods longer than 1 month were taken as abnormal. Patients with abnormal liver function tests owing to HCV unrelated causes (drugs, alcohol, or other toxic substances, other viruses, etc.) were excluded from the study. Forty-eight of these patients underwent at least one liver biopsy. RESULTS: Of the 82 patients, 34 (41.5%) had persistently normal (liver biopsy revealed normal or minimal changes in 77.0%, chronic persistent hepatitis in 15.3%, chronic active hepatitis in 7.7%; no patient had cirrhosis), 29 (35.3%) intermittently abnormal (liver histology was consistent with minimal changes in 50%, chronic persistent hepatitis in 27.8%, chronic active hepatitis in 16.7%, cirrhosis in 5.5%), 19 (23.2%) persistently abnormal (liver biopsy showed minimal changes in 41.1%, chronic persistent hepatitis in 17.6%, chronic active hepatitis in 35.3%, cirrhosis in 5.9%) transaminase values. CONCLUSION: Although continuously or intermittently elevated transaminases do not always indicate morphologically advanced disease, the normal course of serum transaminases is mostly accompanied by normal, or near-normal, liver histology, in HCV-infected renal transplant patients. Liver biopsy is not indicated in deciding disease severity in these patients unless clinical findings dictate otherwise.     

Should patients with chronic hepatitis C infection be transplanted?

Chronic hepatitis C (HCV) infection affects more than 170 million people throughout the world and 2 to 3 million Americans. End-stage liver disease secondary to chronic HCV infection is the most frequent indication for liver transplantation in this country. Currently, the gold standard for treatment for immunocompetent patients is a combination of peginterferon (PEG-IFN) and ribavirin for 6 to 12 months depending on the genotype. This treatment achieves a sustained virological response (SVR) in 54% to 61% of patients overall. Almost 50% of patients do not respond or have recurrences posttreatment and progress in over 10 to 20 years into chronic liver disease and its complications. Liver transplantation is the only therapeutic modality that impacts on quality of life and survival of these patients. However, recurrence of HCV in the new allograft is universal with accelerated progression to cirrhosis in 5 to 10 years. Response to treatment is usually low (20% to 30%), and associated with significant side effects and depression. A significant percentage of patients with recurrent HCV after transplantation require retransplantation to control the complications of end-stage liver disease. Other solid organ transplants recipients already HCV-positive, or infected at the time of transplantation from blood transfusions or an infected graft, develop accelerated, progressive liver disease facilitated by the adverse effects of immunosuppression in addition to HCV replication. To prevent morbidity, mortality, and high costs related to the consequences of HCV infection, all solid organ transplant candidates should be tested for HCV infection and treated appropriately with PEG-IFN and ribavirin prior to transplantation.     

Hepatitis C in chronic renal failure patients.

The occurrence of hepatitis C virus (HCV) infection amongst chronic renal failure (CRF) patients in our Nephrology Unit was investigated over a period of 1 year. A total of 71 patients was studied comprising 26 chronic haemodialysis (CHD) patients, 6 acute haemodialysis patients, 4 peritoneal dialysis patients and 35 CRF patients not on dialysis. Patients were screened before and after haemodialysis, and their baseline and postdialysis values of liver enzymes were determined. Eleven (15.5%) of the total 71 patients were HCV antibody positive. Analysis of the individual patient groups showed that 8 (30.7%) of the 26 CHD patients were positive for HCV. Our data showed a statistically significant relationship between seroconversion and duration of dialysis (p < 0.05). A high statistically significant (p < 0.0001) correlation was observed between the HCV antibodies and CRF. The relative risk of hepatitis C was about 22 times greater for those with CRF compared with the normal controls, which makes CRF an important risk factor. A high proportion of the HCV seroconverters had elevated liver enzyme (serum glutamic pyruvic transaminase). The data presented show a positive correlation between HCV seroconversion, CRF, duration on dialysis and elevated serum liver enzymes.     

Hepatitis C in haemodialysis and nonuraemic patients: A histopathological study

Hepatitis C virus (HCV) is the major cause of posttransfusion non-A, non-B hepatitis. Haemodialysis patients carry the risk of HCV infection. The aim of this study is to compare the morphological changes related to chronic HCV infection found in haemodialysis and nonuraemic patients. Liver biopsies from nine haemodialysis patients and 37 patients with normal renal function were studied. This study shows that haemodialysis patients may have less active and progressive chronic hepatitis C than patients with normal renal function. The number of patients in this study is limited, therefore further studies are needed for definite conclusion.     

Natural history of acute HCV infection in hemodialysis patients

AIMS: Chronic liver disease develops in the majority of non-uremic patients with hepatitis C virus (HCV) infection. The aim of this study was to analyze the evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up study on HCV infection was conducted in 3 HD units from April 1990 to June 2001 to study clinical outcomes after acute hepatitis C. A total of 781 patients were tested monthly for alanine aminotransferase and anti-HCV in serum. In this period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver disease in the follow-up was evaluated by means of biochemical (increased ALT) and virological criteria (HCV-RNA+). The transmission mechanism, the apparition of anti-HCV, clinical manifestations and mortality were also investigated. RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic viremia and high transaminase levels) with a median follow-up of 3 years (range 1 - 6). Five of them who underwent liver biopsies had histologic signs of chronic active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up. In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of them died in the follow-up, acute hepatitis C infection was not a short-term independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved to chronic liver disease. It is important to stress that HCV infection spontaneously cleared in 4 out of 19 patients (21%).     

Antibodies to hepatitis C virus (HCV) in chronic renal failure (CRF) patients on conservative therapy: prevalence, risk factors and relationship to liver disease

There are no data regarding HCV prevalence in CRF patients notrequiring dialysis. In order to assess prevalence and risk factorsfor HCV infection in CRF patients on conservative therapy wetested, by second-generation assays such as Ortho 2 and 4-RIBA,221 predialysis CRF patients attending our Department. Forty-four(20%) patients were anti-HCV positive. Anti-HCV positivity wasrelated to blood transfusion requirement, past or current elevationsof transaminase levels and, to a lesser degree, CRF duration.The prevalence of anti-HCV positivity among CRF patients whowere never transfused was about 10 times higher than that ofblood donors. Our data show that predialysis CRF patients shouldbe considered a specific risk group for HCV infection; bloodtransfusion history and duration of CRF are risk factors foracquisition of HCV infection; HCV infec tion may play a rolein the development of liver disease in this clinical setting.     

Efficacy and tolerance of interferon-alpha(2b) in the treatment of chronic hepatitis C virus infection in haemodialysis patients. Pre- and post-renal transplantation assessment.

BACKGROUND: Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, particularly following renal transplantation. METHODS: In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. RESULTS: Nineteen HCV RNA-positive patients received 3 x 10(6) U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27+/-5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21+/-8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). CONCLUSIONS: It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.     

Travel-associated acquisition of hepatitis C virus infection in patients receiving haemodialysis.

BACKGROUND: It has been proposed that hepatitis C virus (HCV)-infected patients with end-stage renal disease undergoing maintenance haemodialysis may lack HCV antibody (anti-HCV) despite chronic HCV viraemia. This carries important implications for the design of surveillance policies. METHODS: To characterize the prevalence of antibody-negative/RNA-positive HCV infection, patients attending seven haemodialysis units underwent anti-HCV testing using a third-generation assay and HCV RNA testing using real-time PCR. RESULTS: At screening, anti-HCV prevalence was 12/360 (3.3%; 95% CI 1.7-5.8%); 7/12 (58.3%) anti-HCV positive samples were HCV RNA positive. Among anti-HCV-negative samples, 2/348 (0.6%; 95% CI 0.2-2.1%) tested HCV RNA positive (genotype 1a). Retrospective testing of stored sera dated the infections to a period of holiday in the Indian subcontinent. The two infections were unrelated by HCV-NS5B sequencing. Only one of the two newly infected persons showed raised transaminases. Both developed anti-HCV within 8-13 weeks of follow-up. Prospective surveillance of travellers to resource-limited countries returning to the units showed a HCV incidence of 4/153 travel episodes (2.6%; 95% CI 0.7-6.6%) among 131 persons (3.1%; 95% CI 0.8-7.6%). CONCLUSIONS: Among haemodialysis patients in the United Kingdom, antibody-negative/RNA-positive HCV status is associated with newly acquired infection, rather than lack of antibody responses in chronic HCV infection. There is a significant risk of HCV infection associated with travel to resource-limited countries. Given that transaminase levels may be normal, HCV RNA testing is recommended in patients re-entering a dialysis unit following haemodialysis in settings where suboptimal infection control policies pose a risk of exposure to blood-borne viruses.     

Hepatitis C. Virology,transmission modes,clinical aspects,prevention and therapy

Of the various forms of chronic viral hepatitis, in Germany 60-70% are caused by the hepatitis C virus (HCV). The virus arrives inconspicuously, i.e. an acute infection only leads to an increase in transaminases in 40% of cases and to an increase in bilirubin in only 20%. However, approximately 90% of infections take a chronic course and in 20% this leads to cirrhosis after only 20 years. The infection rate of medical personnel is not significantly higher than in the general population. The transmission of HCV from patients to medical personnel, e.g. by needle stick injuries, is very rare and the risk of infection is less than 1%. Even less frequently transmission of HCV in the reverse direction from medical personnel to patients occurs. An active or passive prophylactic immunization is not possible and protective immunization is not yet foreseeable. Recently, progress has been made with chemotherapeutical treatment of HCV. The present state-of-the-art is pegylated interferon-a in combination with ribavirin. The success rate in HCV genotypes 2 and 3 is clearly higher with 70-80% than in genotypes 1 and 4 with approximately 40%. Both drugs have significant side-effects but better forms of medication are not yet available.     

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.     

Course of patients with chronic hepatitis C virus infection undergoing heart transplantation

OBJECTIVE: The objective of this study was to describe the clinical course of patients with chronic hepatitis C virus (HCV) infection undergoing heart transplantation (HT). MATERIALS AND METHODS: Among 499 patients transplanted in our hospital between January 1989 and September 2006, 11 subjects (2.2%) had chronic HCV infection. We analyzed liver function laboratory parameters pretransplantation as well as at 3, 6, 12 months, and last available, pre- and postsurgical hepatobiliary ultrasounds, and mortality. The mean time since HT was 32 +/- 23 months. RESULTS: No abnormalities in the liver parenchyma were observed on the ultrasound examinations performed before or after transplantation. There were 3 deaths (27%), none of which was related to HCV infection. Liver function laboratory parameters remained stable during the follow-up. CONCLUSIONS: The clinical course of patients with chronic HCV infection undergoing HT whose presurgical assessment did not show significant liver damage was favorable. No morphological or laboratory abnormalities were observed that would suggest reactivation of the infection during the follow-up.     

Clinicopathological features of rapidly progressive hepatitis C virus infection in HCV antibody negative renal transplant recipients

Background. Hepatitis C virus (HCV) infection acquired during dialysis treatment generally shows a relatively benign course after renal transplantation (RTx). However, less is known about the course of HCV infection acquired during or after RTx. Methods. Clinical and histopathological assessment of 15 renal transplant recipients who acquired HCV infection during or after RTx. Results. Alanine aminotransferase levels rose for the first-time 1-19 weeks after RTx. HCV RNA was found positive in all patients, but anti-HCV became positive in only nine of them. During a mean follow-up of 21±12 months, jaundice appeared in 12 patients while ascites and/or hepatic encephalopathy occurred in six. Azathiprine was stopped in all patients. Cyclosporin was also stopped in four patients and in two of them prednisolone was also interrupted for a period of 3-7 weeks. Following this, ascites, hepatic encephalopathy and biochemical disturbances improved, while no deterioration was seen in graft function. Nine of the 15 patients had undergone two consecutive liver biopsies (LB). The first LP revealed cirrhosis in three and chronic hepatitis in six patients; the second LB showed cirrhosis in seven patients. The histological activity index (Knodell's score) progressed from 11.8±3.5 to 13.8±3.8. Conclusions. The results suggest that HCV infection acquired during or after RTx may run an unusual and rapidly progressive clinical and histopathological course at least in some of these patients. Decrease or withdrawal of immunosuppressive drugs may improve early hepatic failure without detrimental effect on graft function during that period.     

Prevalence of anti-HCV in patients on long-term hemodialysis

The prevalence of hepatitis C virus (HCV) infection in patients with long-term hemodialysis (HD) in Japan was assessed using an Ortho HCV Antibody ELISA TEST system. Out of 51 patients, 48 of whom had a history of blood transfusions, 15 (29%) were positive for anti-HCV. This figure is much higher than that in other countries (1-20%), and the difference may reflect a select population. Six (33%) of 18 HD patients with chronic hepatic disease were anti-HCV positive. On the other hand, the prevalence of hepatitis B virus (HBV) markers was 39% (20/51), and 7 (35%) of these 20 with HBV markers were also positive for HCV. The prevalence of anti-HCV showed no relation to the duration of HD treatment. Although a correlation between the prevalence and the blood units transfused was not demonstrated, anti-HCV positive patients had received blood transfusions amounting to significantly more units than those given to negative patients. Anti-HCV was detected in approximately one-third of patients with long-term HD, indicating a lower prevalence of HCV infection as compared to that of HBV infection, and patients with hepatitis of type C accounted for about one-third of HD patients with chronic hepatic disease.     

A Six‐Year Follow‐Up After Interferon‐Alpha Monotherapy for Chronic Hepatitis C Infection in Hemodialysis Patients

Interferon‐alpha (IFN) has been accepted as an effective treatment for chronic hepatitis C virus (HCV) infection in hemodialysis (HD) patients. We prospectively assess the long‐term clinical, biochemical, and virological effects of interferon in the treatment of HD patients with chronic HCV infection. This study was performed in 20 HCV‐RNA‐positive HD patients with evidence of chronic hepatitis on liver biopsy. The patients received IFN administered after HD sessions in doses ranging from 3 to 6 million units for 6 to 12 months. The patients were followed up for a period of 6 years with determinations of serial alanine aminotransferase (ALT) levels and serum HCV‐RNA. At the time of the final follow‐up, the patients had no cirrhosis or hepatocellular carcinoma. Among the nonresponder group, only 1 patient died due to sudden cardiac death. Sustained normal serum ALT levels occurred in 9 (45%) of the patients. Nine patients had variable ALT levels, and 2 patients had persistently elevated ALT levels. Eight (40%) patients were continuously HCV‐RNA negative, whereas 12 patients (60%) had variable HCV‐RNA results at the end of the 6‐year follow‐up. These findings show that the long‐term clinical, biochemical, and virological response to interferon monotherapy is good in HD patients with HCV infection.     

Outcome of heart transplantation in patients previously infected with hepatitis C virus.

The lack of knowledge about the course of hepatitis C virus infection (HCV) before heart transplantation (HTx) prompted us to describe our experience with 4 such patients who presented with positive HCV serology before surgery. Two experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of the patients developed signs of hepatic insufficiency during the follow-up (mean 3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA was detected in 81% of the measurements, showing that virus detection techniques seem to be more sensitive than serology techniques in detecting HCV infection in this group of patients. Although immunosuppression promotes active HCV replication, it does not seem to change the chronic features of HCV infection during the first years in patients with good liver function.     

Acquisition of hepatitis C virus in hemodialysis patients: a prospective study by branched DNA signal amplification assay

Serological data indicate that hepatitis C virus (HCV) infection is very common among chronic hemodialysis (HD) patients. Circumstantial evidence suggests that hemodialysis per se is an important risk factor for this infection. We used a novel methodology, the branched DNA (bDNA) signal amplification assay, which is capable of detecting HCV RNA and of quantifying HCV viral load in serum, to prospectively determine the rate of acquisition of HCV infection in 274 anti-HCV-negative patients undergoing HD treatment in four hemodialysis units. Moreover, we used bDNA testing to analyze the dynamics of HCV acquisition among HD patients, a high-risk group for HCV infection with immune compromise conferred from uremia. Two patients were identified with de novo acquisition during 1 year of prospective bDNA testing. Thus, the HCV incidence was 0.73% per year. De novo acquisition of HCV infection was observed in the absence of identifiable parenteral risk factors. Both patients showed the same pattern of HCV acquisition: they underwent an initial viremic phase that was associated with an increase in alanine transaminase (ALT) activity and that preceded the anti-HCV seroconversion. This was followed by HCV RNA clearance and normalization of ALT activity. Anti-HCV positivity occurred 1 and 2 months after the ALT increase in the first and second patients, respectively. Although HCV incidence was low (0.73%), further research is warranted to set the optimal policy for eliminating the risk of nosocomial transmission of HCV in the HD setting. Our findings show the pattern of HCV acquisition in chronic HD patients and emphasize the need to screen the HD population for ALT measurement combined with anti-HCV testing for detecting hepatitis C. HCV RNA testing can identify HCV before seroconversion in individuals with deranged liver function tests. The acquisition of HCV in HD patients without identifiable risk is confirmed.     

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)     

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.     

Hepatic transplant and HCV: a new playground for an old virus

Hepatitis C virus (HCV) infection is a major global health problem affecting 170 million people worldwide. The majority of infected individuals fail to resolve their infection, with a significant number developing chronic, progressive HCV-related liver disease. HCV infection is the leading indication for liver transplantation and unfortunately, all patients with detectable viral load before transplantation will have rapid, recurrent infection. What remain to be determined are factors contributing to the severity of HCV recurrence. Such factors are unique to the posttransplant setting and include: viral genetic diversity and composition, immunosuppression, donor/recipient age and sex, genetic factors and the liver microenvironment. Importantly, the possibility that the severity of HCV recurrence might be also influenced by factors related to the primary course of disease (i.e. viral set point, previously acquired adaptations of the virus) must be further evaluated. In this sense, recurrent HCV infection should not be regarded merely as another acute infection, but rather, it should be cautioned that problems first arising during the primary course of disease may be accentuated during recurrence. Development of novel therapeutic approaches will require a thorough understanding of viral and host determinants of infection resolution and how these factors may change in the posttransplant setting.     

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.