Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.     

Intra-arterial chemotherapy for muscle-invasive urinary bladder cancer

Mixed cryoglobulinemia is a well-known complication after hepatitis C virus (HCV) infection. We report five cases in which cryoglobulinemia appeared or grossly exacerbated following orthotopic liver transplantation (OLT). Cryoglobulinemia and the associated clinical symptoms resolved or improved in two patients treated with ribavirin after liver transplantation, while plasmapheresis was ineffective in another patient. The mechanism involved in induction of cryoglobulinemia after liver transplantation is unknown. However, the effect of antiviral therapy observed in these patients suggests a correlation between cryoglobulinemia, HCV replication, and possibly hepatocellular disease activity. A larger-scale study is warranted to test the effect of ribavirin on post-OLT HCV-associated cryoglobulinemia.     

Cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia

We describe two women (ages 35 and 36 years) with cerebral ischemia, hepatitis C virus, and mixed cryoglobulinemia. One patient (case 1) was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1, and middle cerebral artery M1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type III), hypocomplementemia, and a high positive test result for rheumatoid factor. In the other patient (case 2), cerebral ischemia and seizures developed in the setting of previously documented mixed cryoglobulinemia (type II), membranoproliferative glomerulonephritis, and hypocomplementemia. In this patient, a brain biopsy demonstrated cerebral infarction. Hepatitis C virus infection was confirmed in both patients by polymerase chain reaction detection of hepatitis C virus RNA. These two cases document the occurrence of cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia. Testing for hepatitis C virus and cryoglobulins should be considered in selected patients with cerebral ischemia of inobvious cause.     

Renal failure associated with hepatitis C virus infection. Improvement in renal function after treatment with interferon-alpha

Hepatitis C virus infection can result in mixed cryoglobulinemia and associated clinical syndromes including membranoproliferative glomerulonephritis. Reports regarding the efficacy of interferon-alpha (IFN-alpha) in the treatment of patients with membranoproliferative glomerulonephritis and chronic hepatitis C infection have been inconclusive regarding improvement of renal function. We describe two patients with chronic hepatitis secondary to hepatitis C virus complicated by mixed cryoglobulinemia and membranoproliferative glomerulonephritis who developed severe renal failure which resolved after treatment with standard doses of IFN-alpha 2b.     

Neuronal activity in MST and STPp, but not MT changes systematically with stimulus-independent decisions

Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure.     

Sutton''s disease

Acute and chronic liver diseases related to hepatitis viruses are the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limitating factor in these indications. HCV reinfection was demonstrated by demonstrating a sequence homology of the hypervariable region of HCV RNA in 2 patients before and after liver transplantation. HCV reinfection is almost constant, assessed by the persistence of HCV RNA in serum in 90% of cases. Acute lobular hepatitis appeared in 75% of patients at a median of 4 months post-transplantation with extremes between 23 days and 4 years. In our series, the 5 year actuarial rate of HCV acute hepatitis on the graft, chronic hepatitis and cirrhosis was 75%, 60% and 8%, respectively. HCV RNA level is dramatically increased after transplantation and seems to correlate with the occurrence of acute hepatitis on the graft. A positive relationship between genotype 1 b and prevalence and severity of HCV hepatitis on the graft have been suggested in European series. There is no demonstrated way to prevent HCV reinfection. The use of interferon for the treatment of HCV hepatitis on the graft was disappointing due to a poor antiviral effect and the occurrence of chronic rejection episodes in some patients. Promising results of the combination of interferon and ribavirin have been reported and need confirmation. The 5 year survival of patients transplanted for viral C cirrhosis in our Center is 78%. In conclusion, patients with endstage HCV cirrhosis are candidates for liver transplantation. Viral C reinfection is frequent, but medium term survival is good. However, longterm graft and patient survival remains unknown, and methods to prevent and treat HCV reinfection on the graft are needed.     

Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis

BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS: These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.     

Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy

The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.     

The paradox of decreasing prices and increasing costs for diagnostic tests, imaging, and drugs in Japan

We have examined the clinical (virological and immunological), histological and immunohistochemical features of liver lymphoid nodules in hepatitis C virus-positive (HCV+)/mixed cryoglobulinemia (type II and III) and chronic hepatitis C. The clinical features of liver disease were found to be similar in all patients. In all these groups, liver lymphoid nodules were observed to a similar extent, being more frequent in earlier phases of liver disease and less in more advanced stages. These data were confirmed by studies in serial biopsy samples taken from individual patients with type II mixed cryoglobulinemia; the loss of lymphoid nodules with progression to more advanced histological stages of disease in these patients was accompanied by a decrease of the serum levels of cryoglobulins (although not statistically significant). By immunohistochemical analysis, the liver lymphoid nodules contained predominantly B cells with a CD5+/bcl2+/Ki67- phenotype, which were always polyclonal in type III mixed cryoglobulinemia and chronic hepatitis C, and monoclonal in type II mixed cryoglobulinemia. These immunological features were consistent with an active role of the immune system in HCV-associated liver necro-inflammation. Only in type II mixed cryoglobulinemia was there a clonal restriction of B cells. The immunological profile (autoantibodies) and viral genotypes were examined in some patients, but no significant correlation with clinical and immunohistochemical findings was found; however, the prevalence of genotype 2a was significantly higher in type II mixed cryoglobulinemia than in type III and chronic hepatitis without cryoglobulinemia.     

Viral hepatitis and kidney transplantation

Many etiologic factors can cause hepatic dysfunction in renal transplant recipients. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the major causes of hepatitis in such patients. Taiwan is an endemic area for HBV infection, and HCV infection is also quite common among Taiwanese patients with end-stage renal disease. Whether renal transplantation can be safely performed in these patients is controversial. Advances in understanding of the natural course and improved treatment results in viral hepatitis patients in recent years have gradually improved the outlook for renal transplantation in such patients. Because of the severe shortage of organ donors worldwide, research efforts have also been directed at studying the safety and feasibility of using kidneys from donors infected with HBV or HCV. Short-term results are good for renal transplantation in HBV- or HCV- infected recipients, as well as for recipients who receive HBV- or HCV- infected kidneys. Long-term results show that these patients are at greater risk for hepatic disorders and have poorer outcomes than cohorts without infection, although their survival is better than that of patients with HBV or HCV infection who remain on dialysis. To plan effective treatment strategies, renal transplant physicians should be alert to the occurrence of hepatitis among these patients and realize its impact on renal transplant recipients in terms of increased morbidity/mortality and altered pharmacokinetics of immunosuppressive drugs. Hepatitis in renal transplant recipients is a great challenge for both transplant physicians and hepatologists. Many unresolved issues need further investigation.     

A PET study on cortical and subcortical control of pelvic floor musculature in women

The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an "inapparent" coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an "inapparent" coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6-12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5'NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all "responders" (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.     

Mixed cryoglobulinemia as a model of systemic vasculitis

Leukocytoclastic vasculitis is the dominant lesion of mixed cryoglobulinemia (MC). The high prevalence of antibodies to hepatitis C virus (HCV) in association with the higher concentration of HCV RNA genomic sequences in the cryoglobulins suggests a close relationship between MC and HCV infection and strongly supports the view that this virus plays a key role in causing vascular damage. Analysis of the composition of immune complexes (ICs) provides evidence that cryoglobulins include virions mostly bound to IgG that is specifically reactive with HCV-related proteins, which in turn are crosslinked by monoclonal IgM with rheumatoid factor (RF) activity, frequently bearing the WA crossidiotype (XId). This structure is similar (if not identical) to that of circulating ICs from HCV-infected patients without cryoglobulins, suggesting that the virus may be directly responsible for the production of WA RF. Evidence for the role of circulating cryoproteins in the pathogenesis of cutaneous and renal vasculitis stems from the demonstration of HCV-related proteins and/or HCV RNA genomic sequences in the vessel wall of patients with MC. Our data indicate that endothelial cells are fully susceptible to infection by and replication of HCV, and support the contention that they serve as sufficient targets for the binding of HCV proteins expressed on the cell surface to serum immunoglobulins. The in situ demonstration of IgM RF WA XId adds further evidence that RF of the WA group participates in the development of vasculitis and probably stabilizes the binding of IgG antibodies. Lymphocytes may be crucial in the infection of endothelial cells by acting as a circulating viral reservoir. After encouraging initial results, controlled trials have defined the substantive efficacy of IFN-alpha in the treatment of MC. A response of IFN can be achieved in more than 50% of patients and includes improvement of cutaneous vasculitis and renal function. This clinical response is accompanied by a reduction in hepatitis C viremia, serum cryoglobulin concentration, and IgM RF synthesis. However, almost 80% of responders eventually have a clinical and biochemical relapse. Additional studies are required to improve the outcome and extension of this therapy, define the best candidates, and indicate the situations in which it is needed.     

Posttransplant liver granulomatosis associated with hepatitis C?

BACKGROUND: Liver granulomatosis is an occasional finding in posttransplant liver biopsies. Its diagnosis is made more difficult by the variety of conditions that can lead to it. In the nontransplant setting, the association of liver granulomatosis and hepatitis C virus (HCV) infection has occasionally been described. METHODS: We describe the case of a patient with a liver transplantation for an HCV-associated cirrhosis who developed an alteration of liver tests. Granulomatosis was detected on the liver biopsy. RESULTS: Other causes of granulomatosis were satisfactorily excluded. The development of the lesions coincided with a viral flare-up. CONCLUSION: We think that HCV can be listed among the possible causes of liver granulomas in the posttransplant setting and that it must be considered in the differential diagnosis of this condition.     

Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia

Hepatitis C recurrence after liver transplantation is a serious problem, leading to increased graft loss and morbidity in some individuals. Treatment with interferon and other agents is controversial and not highly efficacious. The use of an effective antiviral agent to reduce or eliminate viral burden is desirable. To this end, we performed an open-label pilot trial to determine if rimantadine would show antiviral activity against hepatitis C virus (HCV) in the posttransplantation setting. Eleven patients with recurrent post-liver transplantation disease, characterized by transaminase level abnormality and HCV RNA in serum and liver biopsy specimens consistent with HCV infection were offered enrollment onto the study. Patients were treated for 12 weeks with rimantadine, 100 mg orally twice daily, and followed up after treatment for up to 8 additional weeks. Serum was collected at 2-week intervals to assess transaminase and HCV RNA levels. Nine patients completed the planned course of therapy. There was no significant change in serum alanine aminotransferase levels during treatment. No patients cleared HCV RNA from the serum, and fluctuations in the viral titer were not clearly associated with the initiation and completion of the active-treatment phase. Rimantadine was well tolerated, with only one patient who stopped therapy for perceived side effects. We conclude that rimantadine monotherapy has no role in the management of recurrent hepatitis C after liver transplantation.     

Histological and clinical outcome after liver transplantation for hepatitis C

Hepatitis frequently recurs after liver transplantation for hepatitis C. However, the histological progression of disease, predictors of recurrence and disease severity, and patient survival remain uncertain. Fifty-five patients with cirrhosis caused by chronic hepatitis C underwent liver transplantation between January 1990 and December 1993. Hepatitis C genotype was determined, and liver biopsies were performed at frequent intervals posttransplantation. The median follow-up time was 40.4 months. The cumulative rate of survival was no different in liver transplant recipients for hepatitis C than in liver transplant recipients for other chronic liver diseases (P = .62). Histological recurrent hepatitis C developed in 33 of 50 patients assessable for disease recurrence; the median recurrence-free survival time was 13.4 months. Histological activity and stage were mild in most cases. Only 2 patients developed cirrhosis, and no patient required a second transplantation for recurrent disease. Patients with acute cellular rejection had a shorter recurrence-free survival (P = .0141). In patients with recurrent hepatitis, rejection also was correlated with increased histological grade 2 years after transplantation (P = .0061). Recurrence-free survival was decreased in patients infected with genotype 1 (1a and 1b combined) compared with genotypes 2 and 3 combined (P = .02), whereas there was no difference between genotypes 1a and 1b (P > .80). Only patients infected with genotype 1a or 1b developed bridging fibrosis or cirrhosis. In addition, patients who had an early recurrence had a greater risk of progressing to bridging fibrosis or cirrhosis (hazard ratio, 5.1; P = .0473). In our experience, recurrent hepatitiS C after liver transplantation in most cases is mild and survival is unaffected. Both acute cellular rejection and infection with genotype 1 are independent risk factors for reduced recurrence-free survival, and early recurrence is associated with a higher risk of disease progression.     

Pepscan mapping and fusion-related properties of the major phosphatidylserine-binding domain of the glycoprotein of viral hemorrhagic septicemia virus, a salmonid rhabdovirus

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.     

Response of patients with dual hepatitis B virus and C virus infection to interferon therapy

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.     

Major types of epilepsy surgery

We evaluated the impact of concomitant infection with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) on the clinical course after renal transplantation (Tx). In 335 patients (pts) transplanted between 1991 and 1993 we found 30 (9%) recipients who were positive for Hepatitis B surface antigen (HBsAg) (ELISA, Organon) and anti-HCV antibodies (immunoblot assay Lia Tek) preTx. Chronic liver disease (CLD) (two-fold or greater increase in serum ALT and AST levels for at least six months) developed in 40.7% coinfected pts as compared to 24.4% and 25.7% pts infected only with HCV or HBV, respectively. Maintenance immunosuppression consisted of P + Aza + CsA, mean follow-up time was 28 +/- 15 months. The mean time of the onset of CLD was 3.0 months (range: 1-18 months) after Tx. Percutaneous liver biopsy performed in 5 CLD pts revealed chronic active hepatitis (CAH) in 4 and chronic persistent hepatitis (CPH) in 1 pt. Four pts who had CAH and were positive for HCV RNA (RT PCR) in serum and for HBcAg in liver tissue, received interferon-alpha therapy for 6 months. Clinical improvement of liver function was observed in all of them, but none cleared HBsAg or HCV RNA. One pt lost his graft due to acute rejection. Concomitant infection with HBV and HCV is associated with the high risk of development of CLD early after Tx. We recommend that pretransplant evaluation of both anti-HCV and HBsAg positive pts should include liver biopsy to exclude potential recipients with CAH.