Significance of "anti HBC alone" serological profile in 284 patients suspicious of being infected with hepatitis B virus

The "anti-HBc alone" serological profile is a frequent finding in hepatitis B virus infections, but little is known about its clinical significance. The aim of this study was to explore the 'anti-HBc alone' serological profile obtained by immunosorbent assay (ELISA) in 284 patients suspicious of being infected with hepatitis B virus. Sera were screened for following serological markers: HBs Ag, anti-HBc and anti-HBs antibodies using immunoradiometric assay (IRMA) and for HBV DNA using polymerase chain reaction. Among 284 studied sera with 'anti-HBc alone' serological profile, 124 were positives for anti-HBs antibodies by IRMA and corresponding to a recovered form of hepatitis B. Nineteen sera were negatives for anti-HBc antibodies, suggesting false positive results by ELISA. Two sera were found positives for HBs Ag by IRMA, which are related to authentic hepatitis B. HBV DNA was positive in 4 sera, suggesting occult hepatitis B. This study indicates that "anti-HBc alone" serological profile is most often correlates with recovered hepatitis B infection, but it can mask an occult hepatitis B.     

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction

Serum hepatitis B virus (HBV) DNA was assayed using polymerase chain reaction, in 107 HBsAg-negative normal Chinese subjects. The results showed that eight subjects (7.5%) had HBV DNA. In the subgroup with antibody to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), 7.3% (5/68) were positive for HBV DNA; HBV DNA was not detected in six individuals with anti-HBs only and in nine with anti-HBc only. In four persons with anti-HBc and anti-HBe, one had HBV DNA. In 20 subjects negative for all hepatitis B serological markers, two (10%) were found to have HBV DNA. This study indicates that serological markers are not adequate to rule out HBV infection, and it further implies that present blood donor screening methods may need improving.     

Vaccination against hepatitis B virus at the Lyon Pasteur Institute. A seven-year evaluation]

Results of immunization against hepatitis B among Pasteur Institute staff members are reported. Prior to immunization, 439 subjects were tested for hepatitis B virus (HBV) markers, including HBs antigen, anti-HBs antibody, and anti-HBc antibody (Ausria, Ausab, Corab assays; Abbott). Forty-seven subjects tested positive for anti-HBs antibody. 317 subjects negative for all the HBs markers studied were given three intramuscular doses of Hevac B (Pasteur vaccins) at one-month intervals. Anti-HBs antibodies were assayed after the third injection with the following results: mean titer, 1,454 mIU/ml, standard deviation, 5,349 mIU/ml, and range, 4 to 41,100 mIU/ml. Anti-HBs titers above 10 mIU/ml were found in 879.4% of subjects. Non-responders and weak responders (anti-HBs titer under 10 mIU/ml) were given a fourth dose of vaccine. Ultimately, after the last (third of fourth) injection 97.6% of subjects had protective antibody titers. No case of HBV infection was seen during the seven-year follow-up period.     

Significance of isolated anti-HBc seropositivity by ELISA: implications and the role of radioimmunoassay.

Hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) are excellent markers for HBV infection and its immunity. The significance of isolated antibody to HBV core antigen (anti-HBc) seropositivity is not certain. To elucidate this, sera from 638 Chinese adult subjects, aged 18-52 years, seronegative for both HBsAg and anti-HBs, were tested for anti-HBc. Fifty-one (8%) were found to have an isolated anti-HBc seropositivity by ELISA, and all were negative for IgM-anti-HBc. The anti-HBc persisted in all subjects who attended follow-up for hepatitis B vaccination (n = 48) for a period of 8 months. These 48 subjects received 3 doses of hepatitis B vaccine (HB-VAX, 10 micrograms or 20 micrograms) at 0, 1, and 6 months: 72.9% developed a primary anti-HBs response (suggestive of a false-positive anti-HBc seropositivity), 4.2% developed an anamnestic or secondary anti-HBs response, and 22.9% did not develop an anti-HBs response. Increasing the cutoff point of the ELISA or reconfirmation with radioimmunoassay (RIA) reduced only a minor half of the false positives. This low specificity of anti-HBc ELISA/RIA, together with the high rate of anti-HBs response to hepatitis B vaccine, indicates that subjects with isolated anti-HBc seropositivity should be included in vaccination programs.     

Epidemiological analysis of the significance of low-positive test results for antibody to hepatitis B surface and core antigens

To determine the significance of certain serological test results commonly encountered in hepatitis B virus testing, we reviewed serological test data from nine studies of hepatitis B conducted between 1980 and 1982. Three tests, for hepatitis B surface antigen and for antibodies to hepatitis B surface antigen and hepatitis B core antigen (anti-HBs and anti-HBc), were used to measure hepatitis B virus infection risk in various populations. Two results, low levels of anti-HBs alone and low levels of anti-HBc alone, occurred at constant frequencies (2.72 and 0.4%, respectively), regardless of the prevalence of HBV infection in the population. Positivity for low levels of anti-HBs alone persisted for 1 year in less than one-half of those studied; in addition, response to hepatitis B virus vaccine was augmented in only one-third of this group. Positivity for low levels of anti-HBc alone did not persist in any of 11 persons studied. These findings indicate that presently available tests for anti-HBs and anti-HBc at low levels are often nonspecific and should be interpreted with caution.     

Isolated core antibody hepatitis B in sub-Saharan African immigrants

Chronic hepatitis B virus (HBV) infection is a major health problem in sub-Saharan Africa, where prevalence is > or =8%, and is increasingly seen in African immigrants to developed countries. A retrospective audit of the medical records of 383 immigrants from sub-Saharan Africa attending the infectious diseases clinics at the Royal Melbourne Hospital was performed from 2003 to 2006. The HBV, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) serological results are reported, with a focus on the isolated core antibody HBV pattern (detection of anti-HBc without detection of HBsAg or anti-HBs). Two-thirds (118/174, 68%) of those tested had evidence of HBV infection with detectable anti-HBc. Chronic HBV infection (serum HBsAg detected) was identified in 38/174 (22%) and resolved HBV infection (both serum anti-HBs and anti-HBc detected) in 45/174 (26%). The isolated core antibody pattern was identified in 35/174 (20%), of whom only 1/35 (3%) had detectable serum HBV DNA on PCR testing, indicating occult chronic HBV (OCHB). Only 8/56 (14%) patients with negative anti-HBc had serological evidence of vaccination (serum anti-HBs detected). HIV infection was detected in 26/223 (12%). HCV antibodies were detected in 10/241 (4%), of whom 8 (80%) had detectable HCV RNA. Viral co-infection was detected in only 2/131 (1.5%) patients tested for all three viruses. The isolated core antibody HBV pattern was common among sub-Saharan African patients in our study. These patients require assessment for OCHB infection and monitoring for complications of HBV.     

Seroepidemiological studies on hepatitis B and D viruses infection among five ethnic groups in southern Taiwan

In order to compare the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection among five ethnic groups in Pingtung County of southern Taiwan, a total of 240 serum samples were collected from September to October, 1985, from the following five ethnic groups: Taiwanese, Hakka, Mainland Chinese, aboriginal Paiwanese, and aboriginal Rukaiese. Ages of subjects ranged from 5 to 69 years. All sera were tested for hepatitis B surface antigen (HBsAg), surface antibody (anti-HBs), and core antibody (anti-HBc) by radioimmunoassay (RIA). Hepatitis B e antigen (HBeAg) and antibody to hepatitis D antigen (anti-HDV) were also tested for those with HBsAg-positive sera. Results showed that 44.1% of all sera examined were negative for HBsAG but positive for both anti-HBs and anti-HBc; additionally, 24.6% were negative for both HBsAg and anti-HBs but positive for anti-HBc. Only 134 serum samples showed negative results for HBV markers, indicating an HBV infection rate of 88.8%. The anti-HDV positive rate was estimated to be 2.7% among HBsAg-positive subjects. The HBsAg-positive rates among Rukaiese, Paiwanese, Hakka, Taiwanese, and Mainland Chinese were 25.8, 22.5, 16.7, 12.9, and 10.0%, respectively; while the prevalence rates of HBV infection among the above five groups were 94.2, 94.6, 85.4, 87.5, and 82.5%, respectively. Differences in the HBsAg-positive rate and HBV infection rate among these ethnic groups were statistically significant. We conclude that people living in Pingtung County are more frequently infected with HBV when compared with inhabitants in northern Taiwan.     

Seroepidemiology of hepatitis A, B, and D viruses and human T-lymphocyte tropic viruses in Japanese drug abusers

To evaluate the prevalence of hepatitis virus markers and human T-cell lymphotropic virus infections among drug abusers in Japan, serum samples were collected from 91 male drug abusers at the Shinshu University Hospital and the rehabilitation facility in Matsumoto and from 519 healthy male blood donors as controls. Sera were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), immunoglobulin M anti-HBc (IgM anti-HBc), antibody to hepatitis D virus (anti-HDV), antibody to HTLV type 1 (anti-HTLV 1), and antibody to human immunodeficiency virus (anti-HIV). The prevalence of anti-HAV was 13.2% in drug abusers and 10.8% in controls (not significant). The prevalences of HBsAg, anti-HBs, anti-HBc and exposure rate to hepatitis B virus (HBV) were 4.4%, 24.2%, 31.9%, and 35.2%, respectively, in drug abusers and 0.8%, 6.7%, 9.6%, and 9.6% in controls. The exposure rate to HBV was significantly different (P less than 0.001). IgM anti-HBc and anti-HDV were not detected in any sera. Anti-HTLV I was detected in three drug abusers (3.3%) and in one (0.2%) of the controls (P less than 0.01). All sera were negative for anti-HIV in all subjects. Infection with HBV and HTLV I is more common among drug abusers than in the general population of blood donors in Japan.     

HBV and HCV infection in Japanese dental care workers

Protective measures against occupational exposure to the hepatitis B virus (HBV) and hepatitis C virus (HCV) must be taken in order to prevent infection in dental care workers. To determine the best way to protect these workers, our study examined viral hepatitis infection in dental care workers in regions with a high prevalence of HCV infections in Japan. In total, 141 dental care workers (including dentists, dental hygienists and dental assistants) were enrolled. After a questionnaire to elicit demographic information was administered by an oral surgeon, hepatitis B surface antigen (HBsAg), antibody to HBs (anti-HBs), antibody to hepatitis B core antigen (anti-HBc) and antibody to HCV (anti-HCV) were measured. When necessary, HBeAg, anti-HBe, levels of HBV DNA, anti-HBc IgM and HCV RNA in serum were measured. Of the dental care workers included, 68 (48.2%) had been immunized with a HBV vaccine. Only 9 wore a new pair of gloves for each new patient being treated, 36 changed to a new pair only after the old gloves were torn and 24 did not wear any gloves at all. No one was positive for HBsAg or anti-HCV, though 73 (51.8%) and 17 (12.1%) workers were respectively positive for anti-HBs and anti-HBc. The positive rate of anti-HBc varied directly with worker age and experience. Of the 68 workers immunized with HBV vaccine, 51 (75%) were positive for anti-HBs. Of the 63 workers who were not so immunized, 17 (27%) were positive for anti-HBs and 15 of these were also positive for anti-HBc. Immunized workers were more protected against HBV infection than non-immunized workers, indicating that HBV vaccine was a useful measure for protection against the infection. The anti-HBc positive rate was significantly higher among dental care workers than general blood donors, suggesting that frequency of exposure to HBV was greater in dental care workers. HBV vaccination should be made compulsory for all dental care workers who handle sharp instruments.     

The underlying mechanisms for the ‘anti-HBc alone’ serological profile

The serological pattern, “anti-HBc alone”, characterized by the presence of antibodies against the core antigen of hepatitis B virus (anti-HBc) as the only marker of hepatitis B, is not rare in a diagnostic setting. Depending on the prevalence of HBV infection and the patient group investigated, 1–31% of positive anti-HBc results are isolated positive findings. Anti-HBc alone is frequently observed in intravenous drug addicts, HIV-infected individuals, patients who are coinfected with HBV and hepatitis C virus, and pregnant women. However, it is not clear how this profile should be interpreted. Several studies have shown that anti-HBc alone is not only compatible with acute and resolved HBV infection but also with chronic infection. The reasons for the lack of HBsAg and anti-HBs in anti-HBc-alone individuals are not clear, but several mechanisms and possibilities have been suggested that could explain this phenomenon, some of which are delineated in this article.     

Atypical serological profiles in hepatitis B virus infection

During hepatitis B virus (HBV) infection, at least four antigen–antibody systems are observed: HBsAg and anti-HBs; preS antigen and anti-preS antibody; HBcAg and anti-HBc; and HBeAg and anti-HBe. Through the examination of these antigen–antibody systems, hepatitis B infection is diagnosed and the course of the disorder may be observed. Although the serologic findings that allow both the diagnosis of HBV infection as well as assessing of its clinical course are already well established, the dynamics of viral proteins expression and of the antibodies production may vary during the infection natural course. This causes the HBV infection to be occasionally associated with the presence of uncommon serological profiles, which could lead to doubts in the interpretation of results or suspicion of a serological result being incorrect. This paper is dedicated to the discussion of some of these profiles and their significance.     

Antibody detection and kinetics of antibody production during early stages of immunization with hepatitis B virus vaccine

Antibodies to influenza virus and human immunodeficiency virus are detectable in B cells during the early stages of the immune response, prior to their occurrence in plasma. To investigate similar phenomena in a model of immunization against hepatitis B virus (HBV) infection, medical students in Ghana were screened for HBV markers, HBV surface (HBs) antigen (HBsAg), and HBV core antibodies (anti-HBc). Consenting volunteers, 24 of whom were seronegative (susceptible) and 2 of whom were positive for anti-HBc (prior infection), were vaccinated on day 0, day 40, and 6 months. Two sets of 10 blood samples, sequentially collected at intervals of 2 days following each immunization on days 0 and 40, were processed into B-cell lysates and plasma. Solid-phase HBsAg coated on microtiter plates for enzyme immunoassay or nitrocellulose membranes for dot blot assay was used to detect anti-HBs activity by an indirect antiglobulin assay. A commercially procured sandwich immunoassay was used, along with an enzyme-linked immunosorbent assay and a dot blot assay, for the detection of anti-HBs in B-cell lysates and plasma. Following the first injection of vaccine, a single sample of B-cell lysate collected between 5 and 21 days revealed anti-HBs in 18/21 subjects with no plasma antibodies detectable by sandwich immunoassay. After the booster dose was injected on day 40, a single sample of B-cell lysate collected between 44 and 49 days showed anti-HBs in 16/19 subjects, and this was accompanied by plasma antibodies in 8 subjects. In contrast, between 8 and 13 days, both subjects with prior HBV infection showed anti-HBs in B-cell lysates and plasma. Thus, primary immunization with the HBV vaccine appears to transiently elicit low-affinity anti-HBs in B-cell lysates into plasma.     

Acute hepatitis B viral infection in a patient with anti-HBs.

We report a patient with antibody to hepatitis B surface antigen (anti-HBs) but no antibodies to other hepatitis B virus components, who developed acute symptomatic type B hepatitis. The possible explanations for this unusual serological pattern are 1) the antibody-positive status, which developed against only a subdeterminant of hepatitis B surface antigen (HBsAg), arose naturally or as the result of cross-reaction with a variety of antigens; and 2) seroconversion to anti-HBs occurred in response to surface antigen of a mutant strain of hepatitis B virus (HBV). This anti-HBs positivity, in the absence of antibody to hepatitis B core antigen, does not provide natural immunization against HBV infection, and so is not protective. Individuals who are positive to anti-HBs antibody alone which is not elicited by HBV vaccine, should be vaccinated against possible HBV infection.     

Evaluation of hepatitis B virus markers for surrogate testing of hepatitis C]

To evaluate the surrogate markers of non-A, non-B hepatitis virus (es) carriage state, the relationship between antibody to hepatitis C virus (HCV) and antibody to HBc/HBs and liver enzyme (ALT) was sought in Saitama prefecture. Out of 36,642 blood donor samples, 410 (1.1%) samples were positive for anti-HCV. Anti-HCV was found in 1.79% of donors with anti-HBs and/or anti-HBc, which is 1.7 fold of the frequency found in donors (1.04%) negative for anti-HBc/HBs. In contrast to the reports from Europe or USA, a poor correlation of anti-HCV with the serological history of hepatitis B infection was observed. These results indicate that hepatitis B and hepatitis C were transmitted independently in the Japanese, which is more homogeneous socioeconomically than the European or American populations. On the other hand, anti-HCV prevalence was in close correlation to ALT level as observed in the USA and in Europe. As we predicted previously, ALT can be expected to reduce the incidence of post-transfusion non-A, non-B hepatitis, however, anti-HBc can not.     

Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: a multicenter study

Occult hepatitis B virus (HBV) infection in patients with chronic hepatitis C has been found associated with severe liver damage, low response to interferon treatment and increased risk of developing HCC. However, doubts remain on its clinical impact and the sensitivity and specificity of its detection. HBV-DNA was sought by PCR in plasma, peripheral blood mononuclear cells (PBMCs) and liver compartments of 89 patients with biopsy proven chronic hepatitis C, using sets of primers for core ("c"), surface ("s"), and x ("x") regions of HBV genome. Occult HBV infection was defined by the presence of HBV-DNA in at least two different PCRs in at least one compartment. Occult HBV infection was detected in 37 (41.6%) of the 89 patients investigated. It was more frequent (80.8%) in 26 anti- HBs negative/anti-HBc positive patients than in 18 anti-HBs/anti-HBc positive (61.1%, P < 0.01) and 45 anti-HBs/anti-HBc negative (11.1%, P < 0.0001), and more frequently in liver (91.9%) than in PBMCs (62.2%) and plasma (32.4%). No association was found between occult HBV infection and the degree of liver necroinflammation and fibrosis. However, considering the 52 patients without occult HBV infection, 51.4% of 35 patients with genotype 1 and 5.9% of 17 with genotype non-1 showed severe fibrosis (P = 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti-HBs negative/anti-HBc positive and anti-HBs positive/anti-HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs.     

Occult hepatitis B virus infection in patients with leprosy

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.     

Frequent Occult Hepatitis B Virus Infection in Patients Infected with Human Immunodeficiency Virus Type 1

The presence of hepatitis B virus (HBV) serological markers was investigated in 170 patients (137 male, 33 female) infected with human immunodeficiency virus (HIV) type 1. Antibodies to the hepatitis B core antigen (anti-HBc antibodies) were detected in 115 (68%) patients. Of these 115, 14 (12%) were hepatitis B surface antigen (HBsAg) positive, 60 (52%) presented anti-HBs antibodies, and 41 (35%) were anti-HBc positive only. All 115 of the anti-HBc positive samples were tested for HBV DNA by using two polymerase chain reaction (PCR) assays that amplify the core and pre-S regions of the HBV genome, respectively. HBV DNA was detected in 23 samples: 7 of 14 (50%) HBsAg-positive samples, 12 of 60 (20%) anti-HBs-positive samples, and 4 of 41 (10%) samples positive for anti-HBc only. Six samples (all HBsAg positive) were positive in both PCR assays and 17 samples were HBV DNA positive in only one assay. The mean viral load in HBsAg-positive patients was higher than that observed in HBsAg-negative patients. A number of patients were receiving treatment with lamivudine, a drug that interferes with both HBV and HIV replication. However, neither the rate of HBV DNA positivity nor HBV load was significantly different between patients treated with lamivudine and those not treated with this drug. Electronic Publication     

Occult hepatitis B virus infection in Korean patients with isolated anti-HBc

Serological detection of isolated anti-hepatitis B core antibody (anti-HBc) can occur in various scenarios, but the most clinically relevant situation is occult hepatitis B virus (HBV) infection (OBI). The purpose of this study was to evaluate the prevalence and clinical relevance of isolated anti-HBc and of OBI with isolated anti-HBc from an unselected hospital population. A total of 14,253 patients referred for hepatitis B surface antigen (HBsAg)/anti-HBs testing were classified into either the Health Promotion Center (HPC) group or the patient group. For patients who were negative for both HBsAg and anti-HBs, an anti-HBc test was additionally performed. An HBV DNA real-time PCR test was performed on isolated anti-HBc patients, and their demographic and clinical data were reviewed. The measured prevalence of isolated anti-HBc and OBI in isolated anti-HBc patients was 5.9 % and 4.7 %, respectively. Prevalence was higher in males, elderly people, and the patient group than in females, the younger, and the HPC group, respectively. In most cases, the levels of HBV DNA load were very low (less than 200 IU/mL), and most cases of OBI presented without liver disease or history of HBV infection. The prevalence of isolated anti-HBc and OBI are affected by the methods of detection, subject population, and constituent factors such as sex and age. Although detection of HBV DNA does not always indicate infectivity, highly sensitive standardized HBV DNA tests are needed in clinical settings to exclude the possibility of OBI, especially in the advanced age group.     

High affinity human monoclonal antibodies directed against hepatitis B surface antigen

Peripheral blood mononuclear cells from donors immunized with hepatitis B vaccine (Pasteur Hevac B) were transformed with Epstein-Barr virus. Two polyclonal cell lines, producing antibodies to hepatitis B surface antigen were established and cloned. Seven clones were isolated; they secreted between 10 and 20 micrograms/ml of HBs specific IgG1 kappa or lambda antibody with anti-HBs titer of 300-800 IU/ml. These human antibodies expressed the anti 'a' specificities and had high affinity and avidity; their potential use as reagents for hepatitis B virus detection and for passive immunotherapy is under study.     

No evidence of hepatitis B virus activity in patients with anti-HBc antibody positivity with or without anti-hepatitis C virus antibody positivity.

BACKGROUND: The serological pattern of anti-HBc antibody positivity without both, HBsAg and anti-HBs antibody positivity may be present in up to 4% of the population of Europe and the United States. OBJECTIVES: The aim of the present study was to determine the hepatitis B virus (HBV) activity by detection of serum HBV DNA in patients with anti-HBc antibody positivity only and with confirmed anti-hepatitis C virus (anti-HCV) antibody positivity or without anti-HCV antibody positivity. STUDY DESIGN: A total of 141 patients positive for anti-HBc antibodies only, were investigated on serum HBV DNA load. Patients were classified into two groups: patients with confirmed positive anti-HCV antibodies (group 1) and patients without anti-HCV antibodies (group 2). RESULTS: Demographic data of patient groups were similar. In 66 of 70 patients with anti-HBc antibodies and anti-HCV antibodies (group 1), serum HCV RNA was detected; the remaining 4 patients were HCV RNA negative but the presence of anti-HCV antibodies was confirmed by the line probe assay. In none of the patients, with anti-HBc antibodies and without anti-HCV antibodies (group 2), serum HCV RNA was detected. In none of the patients, serum HBV DNA was detected. CONCLUSION: In this study, serum HBV DNA could not be detected in patients with anti-HBc antibodies only. There seems to be no need for determination of serum HBV DNA in patients without clinical evidence of chronic liver disease. Nevertheless, it would be useful to test patients with progressive liver disease and those, which belong to high-risk groups such as hemophiliacs, intravenous drug abusers, patients on hemodialysis, and immunocompromised patients.