Evaluation of an enzyme immunoassay for hepatitis C virus antibody detection using a recombinant protein derived from the core region of hepatitis C virus genome

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95%) sera from patients in the study group and negative in 38 of the 39 (97%) sera from those in the control group, showing an accuracy of 96%. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

Hepatitis C Virus Infection-Associated Markers in Sera from Blood Donors in Surabaya,Indonesia

Among 2,233 sera obtained from volunteer blood donors, 259 (11.6%) showed elevated alanine aminotransferase (ALT) levels. A second-generation enzyme-linked immunosorbent assay (ELISA) revealed that 23 (8.9%) of the 259 sera were positive for antibodies against hepatitis C virus (HCV), whereas only 9 (1.4%) of 646 sera randomly collected from blood donors with normal ALT levels were positive (P<0.001). The overall prevalence of anti-HCV antibodies among blood donors was estimated to be 2.3%. HCV RNA was detected in 19 (83%) of the 23 anti-HCV-positive sera with elevated ALT levels, and 8 (89%) of the 9 sera with normal ALT levels. Among the anti-HCV-positive sera, IgM anti-HCV was detected in 5 (22%) of 23 sera with elevated ALT levels and in 2 (22%) of 9 sera with normal ALT levels. All of the IgM anti-HCV-positive sera were positive for HCV RNA, irrespective of ALT levels.     

Anti-hepatitic C virus antibodies hidden in circulating antibody/antigen aggregates in HCV-RNA positive patients

The aim of this study was to determine whether antibodies to HCV can be hidden in immunocomplex aggregates in anti-hepatitis C virus (HCV) negative, HCV-RNA positive patients and whether their presence could be related to HCV viral load or HCV genotype. Sera (23 in toto) from patients with elevated alanine aminotransferase (ALT) levels and negative for anti-HCV but positive for HCV-RNA and the immunocomplex aggregates (precipitate with PEG 6000 and glycine 1 M) were studied. The sera were treated using a rapid, simple new ELISA which disrupted the immunocomplex aggregates. Sera from ten patients were tested anti-HCV positive after immunocomplex disruption. No correlation with age, sex, ALT level, viral load or HCV genotype was observed. In some patients anti-HCV antibodies were hidden in circulating antibody/antigen complexes which could be dissociated with a simple, inexpensive and rapid protocol; therefore it can provide a valuable addition to the diagnosis of HCV infection and it may prevent some cases of post-transfusion hepatitis.     

Seroepidemiology of hepatitis C virus infection in Japan and HCV infection in haemodialysis patients

Abstract: Since January 1990, Japanese Red Cross Blood Centres have introduced hepatitis C virus screening with a first-generation ELISA. From April to December 1992, approximately 0.98% among 10905 489 blood donations screened by a second-generation assay were anti-HCV-positive in all Japan. Seropositivity of anti-HCV increased with the age and serum transminase value in both sexes. In blood donors having a history of transfusion, the anti-HCV reactive rate was 7.4%. The results of the study made by the Japanese Red Cross Non-A, Non-B Hepatitis Research Group show the effectiveness of implementation of HCV screening to prevent posttransfusion hepatitis. Consecutive haemodialysis patients with chronic renal failure are at risk for inflection by a variety of blood-borne agents transmitted within dialysis units. Because of their immunocompromised state, they frequently also have an unusual susceptibility to a variety of nosocomial infections, such as HBV, and HTLV-I. We tested the prevalence of anti-HCV in 1423 (848 males and 575 females) haemodialiysis patients from 18 hospitals in Kumamoto Prefecture, Japan using the Orhto first generation anti- HCV screening assay. There were 316 patients (22.2%) positive for HCV antibodies. The second-generation test was positive in most haemodialysis patients who were eractive to the firs-generation assay. The prevalence of HCV infection increased with the duration of haemodialysis, yet there was a high frequency of HCV seropositivity even wihtout blood transfusion. Acquisition of HCV in dialysis patients could be explained by HCV seropositivity even without blood (all haemodialysis are done with disposable kits, and needles), by secondary HCV infection after the immunodeficiency of haemodialysis, or by HCV infection of the kidney or glomerular deposition of immune HCV/anti-HCV complexes leading to chronic renal failure (as with HBV infection of the liver and kidney).     

IgM anti-hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication

Patients with hepatitis C virus (HCV) infection may have different patterns of antibody response to various structural and non-structural viral antigens. We have correlated the serological patterns to the clinical features of chronic infection and to viral replication in 68 HCV-Ab-positive patients with chronic liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38 with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'-non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and the study showed a good correlation between high values of anti-HCV-IgM and the presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM-positive patients (64.8%) and notably in 19 of the 20 subjects with high levels of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the more advanced stages of disease; thus, the clinical pattern of HCV chronic hepatitis seems to be strictly related to the serological pattern and the presence of HCV-RNA.     

Molecular cloning of HCV and clinical application

Abstract: Fifty-five clones encoding epitopes of HCV were isolated from Japanese patients. Their amino acid homology (AAH) to the sequence of prototype (HCV-1) ranged from 47% to 94%. These sequences cover 60% of the HCV genome lacking M/E and NS2 regions suggesting a very low or lacking immunogenecity for these regions. Two test kits for detection of anti-HCV antibody were developed using a combination of a synthetic peptide (AR142) containing the epitope of N14 (QRKTKRSTNRR) having a homology to the core of HCV of | fr | sol 8/11AA and a non-fusion recombinant protein Y19 starting from amino acid number (AAN) 1380 to 1507 in the NS3 region showing a AAH to the HCV-1 of 90%, and a combination of a mixture of three synthetic peptides of S29 AAN of 1–30, 38–65 and 47–74 of the core and a non-fused recombinant protein S4 AAN of 1287–1506 having a 93% AAH of the NS3 region. They showed almost the same order of sensitivity and specificity of the second-generation kits when tested with serum from blood donors and patients with non-A, non-B hepatitis. It should also be stressed that in all of the complete responders of a recombinant α-interferon therapy, the antibody levels against AR142 gradually decreased during and after the treatment. In 1992, studies performed for 125 patients with hepatocellular carcinoma in our clinic shows that of these 16 patients might developed from either chronic non-B, non-C liver diseases or chronic liver diseases caused by mutant(s) of HCV as their serum were negative for HBsAg and second-generation of anti-HCV.     

Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver disease and blood donors

Background: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum of patients with non A-E hepatitis. However, the association of HGV with hepatitis is uncertain.Objective: To determine the HGV prevalence in blood donors and in patients with liver disease and to evaluate a possible correlation between HGV infection and liver disease.Study design: Sera from a total of 113 consecutive patients with chronic liver disease were submitted to a series of liver enzymes and function tests and analyzed for the presence of HBsAg, anti-HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was determined in a group of 87 blood donors.Results: Nine (10%) sera from blood donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and 3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients were HBsAg carriers. Five (4%) patients were double infected (one with HBV+HCV, one with HBV+HGV and three with HCV+HGV).Conclusion: The proportion (10%) of HGV-infected blood donors was very high when compared with other countries. The results did not allow to establish HGV as an etiologic agent for chronic liver disease. The parenteral route was the presumed means of HGV transmission for only one-third of the patients.     

乙型肝炎病人重叠感染丙型肝炎的评价

应用ＥＬＩＳＡ和ＰＣＲ法检测５０２例乙肝病人血清,４０１例ＨＢｓＡｇ阳性血清中,有１１４例（２８．４％）抗－ＨＣＶ和ＨＣＶＲＮＡ双项阳性,２５例（６．２％）ＨＣＶＲＮＡ单项阳性;２１例（５．２％）抗－ＨＣＶ单项阳性。将ＨＢｓＡｇ乙肝病人分成ＨＢＶＤＮＡ,ＨＢｅＡｇ阳性组和ＨＢＶＤＮＡ,ＨＢｅＡｇ阴性组。前者抗－ＨＣＶ阳性率为１１．６％～２０．５％,ＨＣＶＲＮＡ阳性率为１６．２％～２０．５％。后者抗－ＨＣＶ阳性率为２０．２％～５５．６％,ＨＣＶＲＮＡ阳性率为２３％～６０．３％。结果说明长期携带ＨＢＶ者和慢性乙肝病人均可重叠ＨＣＶ感染。ＨＢＶＤＮＡ阳性组抗－ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于ＨＢＶＤＮＡ阳性组     

Hepatitis B and C in the hemodialysis unit of Tocantins,Brazil: serological and molecular profiles

A survey was conducted in the hemodialysis population of the state of Tocantins, Brazil, aiming to assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, to analyze associated risk factors, and also to investigate these viruses genotypes distribution. During January and March 2001, all patients (n = 100) were interviewed at the unique dialysis unit in Tocantins. Blood samples were collected and serum samples were screened for HBV serological markers. Hepatitis B surface antigen positive samples were tested for HBV DNA. All samples were also tested for anti-HCV antibodies and HCV RNA. An overall prevalence of 45% was found for HBV infection (4% were HBsAg/anti-HBc positive, 2% were anti-HBc only and 39% had anti-HBc/anti-HBs markers). Concerning HCV infection, anti-HCV and HCV RNA were detected in 13% and 14% of the subjects, respectively. Three patients were HCV RNA positive and anti-HCV negative, resulting in an overall HCV prevalence of 16%. Univariate analysis of risk factors showed that only shift and length of tile on hemodialysis were associated with HBV and HCV positivity respectively. Among the four HBsAg-positive samples, HBV DNA was detected in three of them, which were identified as genotype A by restriction fragment length polymorphism (RFLP) analysis. All 14HCV RNA-positive samples were genotyped by INNO-LiPA. Genotypes la and 3a were found in 85% and 15%, respectively. The present data show low HBsAg and HCV prevalence rates. The risk factors associated with HBV and HCV positivity suggest that nosocomial transmission may influence in spreading these viruses in the dialysis unit studied.     

Tendency and analysis of the epidemic situation in parenteral virus hepatitis B and C in the Russian Federation and a number of its regions

As revealed in the present survey, during the last 3 years, against a background of decreased number of registered cases of acute hepatitis B (HB) and acute hepatitis C (HC), an increase in the proportion of patients with the chronic forms of these diseases was observed. The incidence rate of carriership of hepatitis B (HBV) and hepatitis C viruses (HCV) is many times greater than morbidity rates in acute and chronic forms of the disease. Such differences could be due to imperfect laboratory and clinical diagnosis. The registered statistics on HBV and HCV carriership included newly detected HBsAg and anti-HCV in the absence of clinical manifestations, which did not reflect the true spread of HBV and HCV in a given territory. The group of HBV and HCV carriers was found to include a considerable proportion of patients with asymptomatic form of HB and HC. It was testing for HBsAg, anti-HCV only without determination of virus replication markers (anti-HBc IgM, HBV DNA, anti-HCV IgM, HCV RNA) that seemingly determined the category of carriers greatly exceeding the true incidence. To obtain reliable epidemiological information, the complex detection of HB and HC infection markers is necessary.     

Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement

This study was performed to assess the utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies in distinguishing between patients with rheumatoid arthritis (RA) and patients with polyarticular involvement associated with chronic hepatitis C virus (HCV) infection. Serum anti-CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA, 8 patients with chronic HCV infection and associated articular involvement and 31 patients with chronic HCV infection without any joint involvement. In addition, we retrospectively analysed sera collected at the time of first visit in 10 patients originally presenting with symmetric polyarthritis and HCV and subsequently developing well-established RA. Anti-CCP antibodies and RF were detected by commercial second-generation anti-CCP2 enzyme-linked immunosorbent assay and immunonephelometry respectively. Anti-CCP antibodies were detected in 23 of 30 (76.6%) patients with RA but not in patients with chronic HCV infection irrespective of the presence of articular involvement. Conversely, RF was detected in 27 of 30 (90%) patients with RA, 3 of 8 (37.5%) patients with HCV-related arthropathy and 3 of 31 (9.7%) patients with HCV infection without joint involvement. Finally, anti-CCP antibodies were retrospectively detected in 6 of 10 (60%) patients with RA and HCV. This indicates that anti-CCP antibodies can be useful in discriminating patients with RA from patients with HCV-associated arthropathy.     

Hepatitis C virus infection from blood and blood products

Abstract: The addition of second-generation HCV epitopes in antibody detection assays has increased the sensitivity and specificity of blood donor testing, to prevent post-transfusion hepatitis non-A, non-B (PTH-NANB), later characterized as Hepatitis C. However, it is not clear whether all HCV infectious donors are detected by second generation anti-HCV testing. Prospective studies on PTH-NANB were left with some unresolved cases. The use of second-generation anti-HCV assays in blood banks presented a problem with a relatively large number of indeterminate reactivities in supplemental assays such as RIBA-2. These indeterminate reactivities may be solved by the use of polymerase chain reaction (PCR). PCR is more and more used as an extra confirmatory assay to resolve RIBA indeterminate results on blood donors. However, a European study on the proficiency of HCV PCR in different countries revealed that only a minority of the reference laboratories perform this test faultness. Lately, third generation RIBA was developed, which was originally designed to resolve RIBA-2 indeterminate cases. RIBA-3 was shown to be more sensitive and specific in early HCV infection and blood donors than RIBA-2. Third generation anti-HCV testing will become standard practice. Some questions, however, remain unanswered. Do we miss any rare HCV infectious donors, of other genotypes, with third-generation assays, based only on the type 1 sequence of HCV? Can we improve HCV detection in the early phase of infection? What is the role of sporadic HCV transmission? How can we standardize HCV nucleic acid detection methods?     

Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada: a public health laboratory study

Demographic information and laboratory test results on 136 169 clinical serum specimens submitted to the public health laboratory in Manitoba, Canada, for hepatitis C virus (HCV) testing between January 1995 and December 2003 were analyzed. The difference in the clearance rates of HCV infection, without therapeutic intervention, and the HCV genotypes infecting First Nation and non-First Nation people were studied. The rates of co-infection of HCV-positive individuals with other hepatitis viruses were also compared between the two study groups. The results of the analyses of the data indicated that there was a 4.4-fold increase in the number of specimens tested and a 4.9-fold decrease in HCV antibody (anti-HCV) positive cases during the study period. The proportion of specimens submitted for testing from First Nation individuals was lower than their proportion in the Manitoba population. Our study also indicated that there was a significantly higher proportion of First Nation patients who had self-limiting infection (patients cleared the infection and became HCV RNA negative without anti-HCV treatment) in comparison to non-First Nation patients. The proportion of First Nation females who had self-limiting infection was significantly higher than non-First Nation females. HCV genotype 1 infection represented more than 60% of HCV infection in Manitoba. The rate of individuals positive for the hepatitis A virus antibody in the HCV-positive population was higher among First Nation than non-First Nation individuals. On the other hand, there were more HCV-infected First Nation patients than non-First Nation patients who were not immune to the hepatitis B virus. The data indicate that fewer First Nation patients seek anti-HCV therapy in comparison to non-First Nation. In conclusion, the differences in the rates of HCV self-limiting infection between First Nation and non-First Nation individuals in Manitoba may reflect the genetic differences between the two cohorts, which may consequently affect the immune response to the HCV infection.     

Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors

To investigate whether exposure to atomic bomb radiation altered the prevalence of hepatitis C virus (HCV) infection or accelerated the progress toward chronic hepatitis after HCV infection, the seropositivity of antibody to hepatitis C virus (anti-HCV) was determined for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. The seropositivity of anti-HCV antibody was 2.5 times higher among those with a history of blood transfusion and 1.2 times higher among those with a family history of liver disease, whereas acupuncture showed no association with anti-HCV. Although the prevalence of anti-HCV was lower for survivors with positive dose estimates than for those with 0 dose (relative prevalence 0.84, P = 0.022), there was no evidence of a smooth dose-response relationship. However, these data suggested that the radiation dose response for chronic liver disease among HCV antibody-positive survivors may be greater than that among HCV antibody-negative survivors (slope ratio 20). In conclusion, no dose-response relationship was found between anti-HCV positivity and radiation dose; a possible increase in the radiation dose response of chronic liver disease among anti-HCV-positive individuals was found. Thus radiation exposure may accelerate the progress of chronic liver disease associated with hepatitis C virus infection.     

Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study

The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality.     

The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria

We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1) infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV) using third generation enzyme-linked immunosorbent assays. Fifty (27.8%) patients had active hepatitis B virus (HBV) infection while 33 (18.3%) tested positive for anti-HCV antibody. Of these infections, 110 (61.1%), 37 (20.6%), and 20 (11.1%) had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients) was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/microl; AIDS defining) when compared to HBV/HIV-only (mean = 377 cells/microl), HCV/HIV-only (mean = 373 cells/microl) and patients with mono HIV infection (mean = 478 cells/microl). Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.     

A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis

Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for hepatocellular carcinoma (HCC). We have utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be identified in HCC. Sera from 37 patients with HCC and 31 subjects chronically infected with HBV or HCV without HCC were investigated. Sera from 116 patients with other cancers, three patients with systemic lupus erythematosus, and 24 healthy subjects were utilized as controls. We report the identification of eight proteins, for each of which autoantibodies were detected in sera from more than 10% of patients with HCC but not in sera from healthy individuals (p < 0.05). Autoantibodies to four of these proteins were detected at a comparable frequency in sera from patients with chronic hepatitis. The other four proteins, which consisted of calreticulin isoforms, cytokeratin 8, nucleoside diphosphate kinase A, and F(1)-ATP synthase beta-subunit, induced autoantibodies among patients with HCC, independently of their HBV/HCV status. Calreticulin, and a novel truncated form of calreticulin (Crt32) we have identified, most commonly elicited autoantibodies among patients with HCC (27%). We conclude that a distinct repertoire of autoantibodies is associated with HCC that may have utility in early diagnosis of HCC among high risk subjects with chronic hepatitis.