HIV-1 and HTLV-I infection in renal transplant recipients.

The prevalence of retroviral infection in renal transplantation remains poorly defined. We tested retrospectively sera from 224 of 331 patients undergoing renal transplantation between 1979 and 1985. Viral antigen based EIA was used for screening IgG antibodies to human immunodeficiency virus (HIV-I) and human T-cell leukemia virus type I (HTLV-I). Positive EIAs were confirmed by Western blot. Six patients (2.7%) were found to have retroviral infection, four with HIV-1 and two with HTLV-I. The four patients with HIV-1 infection were negative before and became EIA and Western blot positive following transplantation. All patients had transient HIV-1 antigenemia documented before antibody was detected. One patient died of Kaposi's sarcoma 2 years posttransplantion with a functioning graft. One is alive and asymptomatic 4 years posttransplant, and two rejected their grafts and are asymptomatic on maintenance hemodialysis. Six patients tested positive for HTLV-I by EIA. Only two patients, however, were also positive for HTLV-I by Western blot, RIPA, and p24 antigen RIA, one prior to and one after transplantation. Both had HTLV-I-positive lymphocyte cultures and remain asymptomatic of retroviral infection 3 years after renal transplantation. A third patient, positive for HTLV-I by EIA, had indeterminate Western blot and negative RIPA, RIA, and lymphocyte culture. Intravenous drug use was not a risk factor for retroviral infection in this patient population. It is likely that patients became infected peritransplantation from blood transfusions. Contamination by donor kidneys, however, cannot be excluded.

Factors that influence serum hyaluronan levels in hemodialysis patients.

Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.

Quantitative detection of hepatitis C virus RNA in patients undergoing hemodialysis.

The purpose of the current study was to detect quantitatively hepatitis C virus (HCV)-RNA among patients undergoing maintenance hemodialysis. Study subjects were 88 patients on hemodialysis at the Miami Veterans Administration Medical Center and the REN Dialysis Unit at the University of Miami School of Medicine. There were 66 men and 22 women, mean age 52 years (range, 22-87 years), and mean duration of dialysis was 2.8 years (range 0.2-12.5 years). Seventy-three percent had a history of blood transfusion. Anti-HCV was determined by enzyme linked immunosorbent assay (ELISA), confirmed by four antigen strip immunoblot assay (RIBA 2.0 SIA). HCV-RNA was quantitated directly in human sera using a branched DNA (bDNA) signal amplification assay. Twenty-seven of 88 (31%) patient samples were found to be anti-HCV reactive by ELISA. Twenty-two of 27 were confirmed reactive, 2 were indeterminate, and 3 were nonreactive by RIBA HCV. Eighteen of 22 (82%) reactive by RIBA 2.0 HVC were found to have detectable (> 3.5 X 10(5) Eq/ml) HCV-RNA levels (mean [&/- SD], 43.3 +/- 35.4 X 10(5) Eq/ml; range 4.9-123.3). No additional cases were identified with reverse transcription polymerase chain reaction (RT-PCR) using 5' untranslated region "nested" primers. HCV-RNA was not detected in four RIBA HCV 2.0 reactive, the two intermediate, or the 64 patient samples nonreactive for anti-HCV. The two epitopes most commonly associated with HCV-RNA were c22-3 and c33c. Sixteen of 18 (89%) patients with detectable levels of HCV-RNA had normal alanine aminotransferase (ALT). Three patients with the highest levels of HCV-RNA were infected with the human immunodeficiency virus. The authors conclude that HCV-RNA by bDNA assay is a sensitive, specific, and simple test that can be used in association with antibody assays and a PCR-based assay to study the prevalence and management of HCV infection in the dialysis setting.

Veterans Administration cooperative study on hepatitis and dentistry.

Personnel in the VA dental facilities were screened for the detection of viral hepatitis and identification of factors implicating infectivity. A total of 963 personnel from 126 dental facilities throughout the United States voluntarily participated in the study. The rate of seroconversion for any hepatitis B markers was approximately 1% per year. Serial positive tests for antibody to hepatitis B core antigen or antibody to hepatitis B surface antigen (or both) were present in 16.2% of dentists and 13.0% of dental auxiliary personnel. Oral and maxillofacial surgeons composed the highest prevalence occupation (24.0%), and clinical personnel composed the lowest prevalence occupation (8.9%). There was a significant association between years in dental environment and serological positivity for viral B infection. The dentists and dental auxiliary personnel had significant linear trends of increasing serological positivity with years in the dental environment. Although a majority of personnel reported wearing gloves while treating high-risk patients or performing invasive procedures, inadequate prophylactic measures were exercised for most patients undergoing a variety of less invasive procedures. The results of the study show the need for an active immunization program against type B viral infection for dental and dental auxiliary personnel, preferably before the initial exposure to the professional environment.

Diagnostic tools in the evaluation of patients with viral hepatitis undergoing liver transplantation.

Familiarity with the diagnostic parameters of viral hepatitis is imperative in the liver transplantation arena. Chronic viral hepatitis B and C are among the most common categories of end-stage liver disease. The preoperative diagnosis, determination of recurrent infection, and the assessment of antiviral therapeutic efficacy are dependent on appropriate virological testing. Furthermore, liver transplant personnel are at a high risk for parenterally transmitted viral hepatitis infection. Knowledge and understanding of the serological patterns of acute and chronic viral hepatitis, as well as recognition of the immune status for one or more of these viruses, will facilitate prevention and treatment of viral hepatitis for these health care providers.

New perspectives in the diagnosis of hepatitis C.

Since the identification and molecular characterization of the non-A, non-B hepatitis virus (HCV) in 1989, a variety of diagnostic tests based on the detection of hepatitis virus antibodies or HCV RNA in the serum have been developed and refined. The enzyme-linked immunosorbent assays (ELISAs) and the recombinant immunoblot assays (RIBAs) exhibit improved sensitivity and specificity for HCV antibodies compared with their predecessors, and the ELISA-3 is at the forefront of HCV screening. Furthermore, the advent of molecular assays that employ quantitative reverse-transcriptase polymerase chain reaction to detect HCV RNA has allowed clinicians to track the natural history of HCV and to monitor the progress of therapy. A role for further refinement of an HCV diagnosis using tests to determine genotype, subtype, and quasispecies is explored. In addition, the role of liver biopsy and non-invasive markers of histologic status are placed into the context of patient prognosis. This article reviews the state-of-the-art tests and assays developed for the diagnosis and management of HCV infection.

Lack of transmission of human immunodeficiency virus in chronic hemodialysis patients.

We carried out a prospective 2-year study on the transmission of human immunodeficiency virus (HIV) infection in a chronic dialysis unit with a high prevalence (11%) of the infection. Only 1 of 45 HIV-negative patients seroconverted, and this was related to the administration of contaminated blood. We conclude that current Centers for Disease Control criteria are sufficient to prevent transmission of HIV infection in dialysis units.

Elevated levels of immunoglobulins and immune complexes in the bile of patients with primary sclerosing cholangitis.

The concentration of immunoglobulins and immune complexes was determined in the serum and bile of four patients with primary sclerosing cholangitis, only one of whom had chronic ulcerative colitis, and in four postcholecystectomy control patients. The result of the immunoglobulin studies demonstrated increased serum levels of IgM in primary sclerosing cholangitis as compared to control patients. The IgG, IgA, and IgM in bile were all significantly elevated as compared to controls (p = 0.02). Immune complexes in bile and serum were also determined in both groups by the C1q and conglutinin binding assays. Immune complexes in bile were elevated in three of four of the patients with primary sclerosing cholangitis. These findings further characterize primary sclerosing cholangitis in terms of biliary immunoglobulins and immune complexes but do not resolve whether these changes are an epiphenomenon or reflect a primary role of immunoglobulins and immune complexes in the pathogenesis of this disorder.

A multicenter study evaluation of the digene hybrid capture II signal amplification technique for detection of hepatitis B virus DNA in serum samples and testing of EUROHEP standards.

We have evaluated the new Digene Hybrid Capture II HBV DNA Test (HCII HBV), which is a 96-well microtiter plate-based signal amplification assay. This test uses hybrid capture technology that specifically detects RNA-DNA hybrids. HCII HBV is able to quantify hepatitis B virus (HBV) DNA at between 1.4 x 10(5) and 1.7 x 10(9) HBV copies per ml in a standard format. By using a modified sample preparation method, which allows the input of 30-fold more serum for an ultrasensitive format, the sensitivity of the assay can be increased reproducibly to approximately 8,000 copies of HBV per ml. By using a combination of these two formats, the assay can quantify over a total range of 6 logs. In our multicenter evaluation study, the mean laboratory-to-laboratory coefficients of variation were 22, 7, and 12% at the three sites, respectively, with a combined specificity of 98.4%. The linearities of both the standard test and the ultrasensitive test were excellent, with Spearman correlation coefficients of 0.997 and 0.999, respectively. Furthermore, the intra-assay reproducibility for the standard assay gave coefficients of variation of from 13 to 33, 9 to 21, and 3 to 8% at the three sites, respectively. HCII HBV was shown to be genotype independent when the EUROHEP standards for genotypes A and D were used. This assay allows the accurate measurement of HBV DNA levels in serum and can be clinically used for the monitoring of responses to antiviral agents for patients chronically infected with HBV.

An institutional outbreak of hepatitis B related to a human biting carrier.

An outbreak of hepatitis B in a residential institution for the mentally retarded was studied. Initially one overt case of hepatitis was noted. A serologic screen of students and employees revealed a total of 12 individuals positive for hepatitis B surface antigen (HBsAg). Subtyping by radioimmunoassay subsequently demonstrated that the population of HBsAg-positive individuals could be subdivided into two groups, based on the HBsAg subtype: adw2 or ayw3. The five individuals with subtype adw2 all were carriers. The ayw3 group, in contrast, were acutely infected except for one carrier with persistent hepatitis B e antigen. Both the ayw3 carrier and several of the acutely infected individuals were aggressive biters. Human biting, a frequent occurrence in the classroom studied, was one probable mode of transmission in this outbreak. The resolution of the outbreak was achieved by rapid screening for HBsAg with subtyping of positive patients and careful observation of the setting for putative modes of transmission.

Recurrence and clearance of hepatitis B surface antigenemia in a dialysis patient infected with the human immunodeficiency virus.

Hepatitis B vaccination programs have prevented infection in many dialysis patients, although the antibody response to vaccination is still insufficient in approximately 50%. Reinfection or reactivation of latent hepatitis B infection (HBV) has been reported in certain groups of immunosuppressed patients, including those infected with the human immunodeficiency virus (HIV-1). We report the reactivation or reinfection of HBV with resurgence of hepatitis B surface antigen in a dialysis patient coinfected with HIV-1. Thus, in dialysis patients with latent HBV infection, with undetectable hepatitis B surface antigen (HBsAg) levels, the potential exists to reactivate during immunosuppression associated with HIV-1 infection and/or end-stage renal disease. Reinfection with a different subtype is also possible. The development of hepatitis B surface antigenemia in this patient population creates a potential for transmission in the dialysis setting. This is of special concern since the number of patients infected with HIV-1 and with evidence of prior hepatitis B infection is increasing in urban units.

Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry.

Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 +/- 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% +/- 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein-conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed. Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors.

Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity.

Hepatitis C-associated hepatocellular carcinoma.

In the United States, a large percentage of patients with hepatocellular carcinoma are serologically negative for hepatitis B. We conducted a retrospective study to determine the prevalence of hepatitis C antibody in the sera of 59 patients with hepatocellular carcinoma who were HBsAg-negative and had no evidence of alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis or alpha 1-antitrypsin deficiency. Twenty patients (34%) were hepatitis C antibody-positive and hepatitis B core antibody-negative. All twenty patients had underlying cirrhosis, and seven (35%) had histories of transfusions. Eleven (19%) additional patients were also hepatitis C antibody-positive but were hepatitis B core antibody-positive as well. Twenty-one (36%) patients were both hepatitis C antibody- and hepatitis B core antibody-negative and seven (12%) were hepatitis C antibody-negative but hepatitis B core antibody-positive. The prevalence of hepatitis C antibody was also determined among three other population groups serving as controls and found to be 14% in 28 HbsAg-positive patients with hepatocellular carcinoma, 44% in 76 patients with cryptogenic cirrhosis and 0.5% in 200 consecutive volunteer blood donors. We conclude that hepatitis C antibody is prevalent among patients with hepatocellular carcinoma and may therefore be a common causative agent of this disease. A significant number of patients with and without cirrhosis, negative for hepatitis C antibody and hepatitis B core antibody, remain without a discernible cause for this malignancy. Perhaps a second- or third-generation test will detect hepatitis C antibody in some of these patients.

Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis.

Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBcAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C100-3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100-3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy-nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis.

Viral pathogenesis of hepatocellular carcinoma in the United States.

Chronic hepatitis B virus infection is closely associated with the development of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus infection as a major pathogenic agent of HBsAg-negative hepatocellular carcinoma. The significance of hepatitis C virus and hepatitis B virus infections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBsAg-negative American patients with hepatocellular carcinoma for evidence of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sensitive polymerase chain reaction was employed to detect hepatitis C virus RNA and hepatitis B virus DNA in serum and liver. Three sets of hepatitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measured with second-generation immunoassays. Twenty-six (29%) of these patients carried low levels of hepatitis B virus DNA in either serum, liver/tumor tissue or both. On the basis of the results from serological and polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infection. When data were combined, 14 patients (15%) had evidence of hepatitis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infected with hepatitis B virus alone and 39 (43%) had hepatitis C virus only. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The spectrum of liver disease in the acquired immunodeficiency syndrome.

Abnormal liver chemistries, unexplained fevers, or hepatomegaly prompted 36 liver biopsies on 34 patients with the acquired immunodeficiency syndrome. The most common finding was the presence of hepatic granulomas, seen in 13 of the biopsy specimens. Eight of these granulomas were ill-defined, and 5 were more clearly associated with mycobacterial disease. Portal fibrosis and fatty infiltration were common, but a paucity of significant inflammatory activity was seen despite elevated aspartate aminotransferase levels, perhaps related to the underlying immunoincompetent status. Other noteworthy histopathologic findings included 1 patient each with peliosis hepatis and cryptococcal hepatitis. Electron-microscopic evidence of cytoplasmic tubular structures or viral particles were seen within the hepatocytes of 2 patients. It is concluded that a broad spectrum of hepatic histopathology may be seen in the acquired immunodeficiency syndrome, and that liver biopsy may be diagnostically valuable in the clinical investigation of such patients.

Improved detection of antibodies to hepatitis C virus in dialysis patients using a second-generation enzyme immunoassay.

We tested serum samples from 99 patients undergoing maintenance hemodialysis for hepatitis C virus (HCV) antibodies using a first-generation, licensed anti-HCV enzyme immunoassay (EIA) and a second-generation anti-HCV EIA that detect three gene products c100-3, NS3, and core. Specimens that were repeatedly reactive by either or both screening assays were further evaluated by testing with supplemental EIAs and a dot blot immunoassay. There was 87.9% agreement between the licensed HCV EIA and the HCV EIA second generation. HCV EIA Second Generation detected 10 more positive specimens than HCV EIA, for an increase in detection from 33.3% (33/99) to 43.4% (43/99). We conclude that HCV EIA Second Generation improves detection of HCV infection in hemodialysis patients.

Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines.

The immunogenicity, tolerability and interchangeability of two hepatitis A vaccines, Vaqta (Merck and Co.) and Havrix (SmithKline) were studied in a randomized, crossover, controlled clinical trial. Vaccine was administered to 201 volunteers at 0 and 26 weeks in one of four vaccine regimens: Havrix-Havrix; Havrix-Vaqta; Vaqta-Havrix or Vaqta-Vaqta. Seroconversion rates (>/=10 mIU/ml) for those whose first dose was Vaqta or Havrix, respectively, were: 41/96 (43%) versus 30/95 (32%) (P=0.15) at 2 weeks and 91/98 (93%) versus 84/97 (87%) (P=0.43) at 4 weeks, and 100% at 26 weeks. Geometric mean concentrations (GMC) of total antibody to hepatitis A virus (anti-HAV) for Vaqta and Havrix were 189 and 114 mIU/ml (P=0.011) at 4 weeks and 234 and 136 mIU/ml (P<0.001) at 26 weeks. At 30 weeks, the GMC after two doses of Havrix was 2612 mIU/ml compared with 5497 after two doses of Vaqta (P<0.001). The GMC in the Havrix-Vaqta group was 5672 mIU/ml compared with 3077 mIU/ml in the Vaqta-Havrix group (P<0.001). Less than half of vaccine recipients reported tenderness or pain. In this study, seroconversion rates of the two vaccines were similar. Vaqta produces significantly higher anti-HAV antibody than Havrix. Crossover immunization is well tolerated and results in high antibody concentrations, especially when Vaqta is the booster dose. The significance of higher anti-HAV antibody concentrations in terms of long-term protection is unknown.

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group.

BACKGROUND AND AIMS: Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including procollogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. METHODS AND RESULTS: Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382+/-31 vs 110+/-9 microg/L respectively, P< 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179+/-11 microg/L) compared with patients without fibrosis (62+/-20 microg/L; P< 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R=0.5421, P<0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 microg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. CONCLUSIONS: Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis.