An epidemic of varicella in rural southern India

Hepatitis B remains a significant risk to patients receiving chronic hemodialysis. Hepatitis B vaccines are effective in providing protection against this infection. However, the minimum antibody level necessary to guarantee an efficacious protection is not clear. Little is known about the effect of this vaccine in persons treated with erythropoietin (EPO) and in patients with hepatitis C virus (HCV) infection. We have studied 36 chronic hemodialysis patients; 17 of them receiving EPO and 9 were diagnosed as having HCV infection. Effective immunity (antibody titer higher than 100 mIU/ml) was observed in 61.1% of the participants and was not influenced by EPO administration, but the effective immunization rate was lower in HCV infected patients (33.3% vs. 70.3%, p < 0.05). These results suggest the possibility that HCV infection may modify the effectiveness of hepatitis B vaccine.     

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.     

Liver transplantation in hepatitis C. A Spanish multi-centre experience

OBJECTIVE: The purpose of this retrospective survey was to determine the prevalence and outcome of hepatitis C virus (HCV) infection in cirrhotic patients undergoing liver transplantation (OLT) in Spain in 1992. METHODS: Post-OLT HCV infection was defined by anti-HCV (second-generation ELISA) and/or PCR. Patients were divided into groups A (HCV-positive pre-OLT: n = 124, 46%) and B (HCV-negative pre-OLT: n = 145, 54%). RESULTS: HCV infection was more prevalent in patients originally diagnosed as having non-A non-B cirrhosis (97%) and cryptogenic cirrhosis (79%) than in patients with cholestatic or metabolic diseases. Group A patients were older (53.3+/-7.9 versus 47.6+/-9.7; P< 0.05) and had a higher prevalence of hepatocellular carcinoma (22% versus 4%, P< 0.05). Post-OLT HCV infection was 99% in group A versus 4% in group B (P< 0.05). Histological hepatitis developed in 39% (66% in group A versus 14% in group B, P< 0.05) with similar follow-up. Chronic rejection occurred in 6% (3% in group A versus 8.5% in group B, P= 0.07). Retransplantation rate (overall 8%) and two-year patient survival did not differ between groups (79% versus 72%). Graft survival was higher in group A (74% versus 65% at 2 years, P= 0.04). CONCLUSIONS: HCV-cirrhosis represented the most frequent indication for OLT in Spain in 1992. While HCV recurrence was universal, de novo acquisition was rare. HCV accounted for most post-OLT hepatitis (87%), but was not associated with chronic rejection, nor with a higher retransplantation rate. Patient survival was not different in HCV patients compared to a control group after a follow-up of 2-3 years. Therefore, at present, HCV-cirrhosis is an acceptable indication for OLT.     

Predictors of patient and graft survival following liver transplantation for hepatitis C

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1994, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P = .02 and P = .003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P = .001). Recipients who had a pretransplantation HCV-RNA titer of > or = 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of < 1 x 10(6) vEq/mL (P = .0001). Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While long-term patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients.     

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.     

Astrocytic pathology in progressive supranuclear palsy: significance for neuropathological diagnosis

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.     

Dorothy and The Wizard. Intergenerational issues in mental health and aging

Among patients undergoing maintenance hemodialysis, a high prevalence of hepatitis C virus (HCV) infection can be observed. In a prospective study, sera of 273 patients were examined for the presence of HCV infection by serological tests and by PCR. Thirty-five patients (12.8%) were HCV antibody positive, and in 31 of them HCV RNA could be detected by PCR. Among the 238 seronegative patients HCV infection was detected in 12 cases (5.0%) exclusively by PCR. Only in 1 of these patients seroconversion could be observed within the 18-month follow-up period. These findings demonstrate that in hemodialysis patients PCR is necessary for the diagnosis of HCV infection.     

Plasma concentrations of antipsychotic drugs in psychiatric inpatients

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.     

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.     

The prevalence of HBsAg in hospitalized children as a marker of hepatitis B virus infection]

The aim of this study was to determine the prevalence of hepatitis B surface antigen (HBsAg) in hospitalised children, as specific marker for hepatitis B virus (HBV) infection. Our study group consists of 517 children, 68 of them diagnosed with chronic hepatitis. For HBsAg determination we used an ELISA test (Labsystems); for some children we also tested by ELISA the following markers: the antibodies and anti-hepatitis C virus (HCV) antibodies. From 517 children 24.28% were HBSAg positive and 75% of children with chronic hepatitis were positive for the same marker. Almost 100% of chronic active hepatitis (CAH) patients was positive for HBSAg. CONCLUSIONS: 1. The prevalence of HBsAg was much higher as compared with the healthy population prevalence; it is a clear prove that HBV infection has an important role in chronic hepatitis appearance. 2. For all HBsAg positive patients, it is necessary to determine other markers like HBeAg-anti-HBe antibodies system as well as markers for other viral hepatitis (HDV, HCV). 3. The anti-HBV infection vaccine will reduce significantly the prevalence of HBV and HDV infections; 4. Biological molecular technique, like PCR will be necessary in our country, in the future, even the price is so high, to monitoring the IFN treatment for chronic infection as unique solution for these patients.     

Chronic hepatitis B and C in HIV-infected patients

BACKGROUND AND AIM: This retrospective study examined the prevalence of co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the frequency of chronic hepatitis in HIV-infected patients with respect to both the different risk groups and the serological results. PATIENTS AND METHODS: All Zurich participants of the Swiss HIV Cohort Study were evaluated who had available results of hepatitis B and C serology and ALT. RESULTS: Of the total 279 patients, 52% belonged to the intravenous drug user, 34% to the homosexual, and 11% to the heterosexual risk category. Serologically, previously acquired infection with HBV alone could be demonstrated in 92 (33%), HCV alone in 9 (3%), and both HBV and HCV in 130 (47%) patients. Only 3% of patients with sexually acquired HIV infection had anti-HCV antibodies, whereas co-infection with HBV and HCV was present in 87% of intravenous drug users. Among the 222 patients with previous HBV contact, 25 (11%) had positive HBsAg and 91 (41%) had "anti-HBc alone", both assumed to represent active HBV infection. 66 (24%) of 279 patients had chronic hepatitis with ALT elevation lasting > or = 6 months. Chronic hepatitis was present in 46% of those with active HBV and HCV co-infection, in 36% of those with HCV infection alone and in 18% of those with active HBV infection alone (P < 0.001). Of the 66 cases of chronic hepatitis, 58 were associated with HCV infection, and only 2 cases had no serological signs of active HBV or HCV infection. CONCLUSION: In patients with sexually acquired HIV infection, HBV had frequently been co-transmitted. In contrast, almost all of those infected by means of intravenous drug use had a co-infection with both HBV and HCV. The latter seems to play the strongest role in the development of chronic hepatitis with persistent ALT elevation. A chronic ALT elevation was almost always associated with serologically active HBV or HCV infection.     

Characterization of overt B-cell lymphomas in patients with hepatitis C virus infection

A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, "essential" mixed cryoglobulinemia (EMC) and Sjogren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.     

Sertraline for premenstrual dysphoric disorder

Symptomatic cryoglobulinaemia is infrequent in HIV-1-infected patients, but a few cases have been described [1-3], occasionally associated with hepatitis C virus (HCV) infection [1, 3]. These cases showed rheumatologic [1] or neurologic manifestations [2, 3], but until now no cutaneous symptoms associated with cryoglobulinaemia in HIV-infected patients have been described. We report what we believe to be the first case of cutaneous, symptomatic cryoglobulinaemia in an HIV-1-positive patient, who, in addition, was HCV-negative.     

ERM proteins: head-to-tail regulation of actin-plasma membrane interaction

Viral infections due to hepatitis C virus in hemodialysis patients are frequent and have a potential risk of progression towards chronicity. Biochemical and viral markers of infection, are transaminases level, anti-HCV serology and the detection of HCV RNA, respectively. A rational strategy based on routine use of these three diagnostic tools is proposed in order to avoid unnecessary assays and to increase in the case of health cost control, the cost/efficacy ratio. The latter is set up, in the sero-negative hemodialysed, on the early detection of infection by the hepatitis C virus in order to consider of a therapeutic which is able to cure patients and to avoid the ineluctable passage towards chronicity; in hemodialysed with positive HCV serology, the detection of HCV RNA allows to establish the infectiosity status of these hemodialysis patients. It is therefore very important to evaluate prospectively this diagnosis approach in hemodialysis patients.     

Structure-activity relationship studies of 4-substituted-2-guanidinothiazoles: reversible inhibitors of gastric (H+/K+)-ATPase

To investigate the incidence of child's HCV infection in our area, 637 children with different background, including 65 posttransfusion cases, 419 hepatitis patients (250 cases of acute hepatitis A, 156 cases of chronic hepatitis B and 13 cases of non-A, non-B hepatitis), 50 infantile hepatitis syndrome (IHS) infants and 103 healthy day-cared children were tested for serum anti-HCV antibody (EIA) and HCV RNA (nested PCR). It was found that posttransfusion children had significantly higher anti-HCV positive rate (30.8%) and HCV infection incidence (43.1%) than hepatitis patients (4.3% and 5.3%), IHS infants (6.0% and 8.0%) and day-cared children (2.9% and 2.9%). 25 of 33 cases with posttransfusion hepatitis (PTH) developed hepatitis C, which was the leading cause of PTH (75.8%) and NANB PTH (25/30, 83.3%). The incidence of HCV infection in NANBH patients was 23.1% (3/13) which was apparently higher than that in day-cared children (P < 0.02) and lower than that in PTH patients (P < 0.001), but not statistically different from that in AHA and CHB patients (P > 0.05). Mother-infant paired study in IHS group showed that 4 pairs of mother-infant had HCV infection, one boy aged 8 months and his mother were anti-HCV positive, and another 3 pairs possessed HCV RNA in sera. 3 of 103 healthy day-cared children were found to have inapparent HCV infection, who were anti-HCV and HCV RNA positive.     

Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

The natural history of chronic hepatitis C in haemophiliacs

Most haemophiliacs treated with non-virally-inactivated clotting factor concentrates have been infected with hepatitis C virus (HCV). We have studied the natural history of chronic HCV infection by following all 138 HCV-positive patients from our centre for periods of up to 28 years. As well as the clinical and biochemical characteristics, we studied 116 liver samples from 63 patients obtained at elective biopsy (n = 103) or autopsy (n = 13). 36 (26%) of the patients were HIV positive, and three were chronic carriers of hepatitis B. Evidence of previous exposure to hepatitis A and B was found in 37.2% and 48.1% respectively. Raised transaminase levels were found in 82.6% of patients. 11 of 15 patients with normal transaminases tested by PCR for HCV RNA were positive, indicating that most patients, even in this group, have chronic hepatitis C infection. Cirrhosis was diagnosed by liver histology in 19 patients, and nine patients developed liver failure. The incidence of cirrhosis rose rapidly 15 years after HCV infection to 15.6 per 1000 person-years. Multivariate analysis showed that HIV status, length of time since HCV infection and age at HCV infection were independently associated with both the development of cirrhosis and liver failure. Two patients developed hepatocellular carcinoma: one of these was exposed only to a single batch of FVIII concentrate 11 years earlier. Chronic hepatitis C is increasingly recognized as a major cause for morbidity and mortality in haemophiliacs, especially those who are HIV positive and who were infected at an older age.     

Hepatocellular carcinomas infected with the novel TT DNA virus lack viral integration

A novel DNA virus designated TT virus (TTV) was cloned from a patient with posttransfusion hepatitis and is thought to be a new hepatitis virus. At present, hepatitis B virus (HBV) and hepatitis C virus (HCV) are known to induce hepatocellular carcinoma (HCC). But, actually, in Japan approximately 5 to 10% of HCCs are in HBV-negative and HCV-negative (NBNC) patients. In order to study the possible role of TTV in hepatocarcinogenesis, we investigated the frequency of the TTV genome in liver tissue of 20 HCC patients. As a result, 3 of 8 NBNC HCC patients and 5 of 12 HBV- or HCV-associated HCC patients were TTV positive, and TTV was shown not to be specific for NBNC HCC. For all TTV-positive patients, we also confirmed that the TTV genome was not integrated into host hepatocyte DNA.     

Detection of hepatitis C virus with RNA polymerase chain reaction in fulminant hepatic failure

The role of hepatitis C virus (HCV) infection in fulminant hepatic failure is controversial. The frequency of serum HCV RNA positivity in previously reported patients with fulminant hepatic failure (FHF) of indeterminate cause ranged from 0 to 12% in the United States and Europe and from 43% to 59% in Asia. We assessed serum HCV RNA using polymerase chain reaction (PCR) and oligoprimers from the 5'UTR of the HCV genome in 26 consecutive patients with FHF. Another laboratory independently performed PCR on 21 of the serum samples using different oligoprimers from the 5'UTR and NS3 region of the HCV genome. Serum HCV RNA was detected in two of seven (28%) patients with hepatitis B, 9 of 15 (60%) with an indeterminate cause, and in none with hepatitis A (n = 2) or drug-induced hepatotoxicity (n = 2). HCV RNA PCR results were concordant between both laboratories in 17 of 21 (81%) of samples. In patients with an indeterminate cause, HCV RNA positivity was significantly associated with the transmission risk factor of low socioeconomic status and Hispanic ethnicity. Eighteen patients underwent liver transplantation (LT) and 15 (83%) survived. Among patients with FHF of indeterminate cause, recurrent or acquired HCV infection after transplantation occurred in three of five (60%) and one of four (25%) patients, respectively. Three of four (75%) patients with hepatitis C virus infection post-LT also developed histologic hepatitis. HCV appears to be the causative agent of a substantial number of cases of FHF classified as indeterminate in the Los Angeles area. Differences in patient populations or risk factors may explain the discordant incidences of HCV infection in FHF observed among different programs.