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PubMed1975

5'-nucleotide phosphodiesterase isoenzyme in patients with hepatitis B infection.

The hypothesis that hepatitis B infection is etiologically related to hepatoma has been investigated by studying the interrelationships between hepatitis B surface antigen (HBsAg, Australia antigen) and the fast-moving 5'-nucleotide phosphodiesterase Band V isoenzyme (5'-NPDase-V). Sera from 58 patients with viral hepatitis were tested for 5'-NPDase-V and HBsAg. The isoenzyme was found in 34 of 37 patients who were also positive for HBsAg but in only 4 of 21 hepatitis patients who were HBsAg negative. Five patients convalescing from hepatitis were negative for both HBsAg and the isoenzyme. Preparative gel electrophoresis showed that these 2 markers were different proteins. Of 34 hepatoma patients, 29 were positive for 5'-NPDase-V. Only 1 isoenzyme-positive patient was positive for HBsAg by counterimmunoelectrophoresis. However, of 16 isoenzyme-positive hepatoma patients available for radioimmunoassay, 8 were NBsAg positive (50%). None of 21 hepatoma samples tested for antibody to NBsAg was positive. Of 21 "normal" carriers of HBsAg and 10 carriers with Down's syndrome, 4 persons were detected with the isoenzyme. The results suggest that HBsAg and 5'-NPDase-V in the presence of liver damage are associated and thus provide a new marker enzyme between hepatitis B infection and hepatoma.

Carcinoma, Hepatocellular↗

PubMed2004

Hepatitis C infection in children with haemophilia: a pilot study.

Many haemophilia patients were infected with hepatitis C virus (HCV) in childhood after transfusion with inadequately or non-virus inactivated clotting factor products. Limited information is available on the clinical course of HCV infection in children. To assess the clinical consequences of hepatitis C in these young patients we performed a pilot study of 31 patients with haemophilia, infected with HCV before the age of 13. Current median age was 20 years. Nineteen (61%) patients had chronic hepatitis C, whereas the remaining 12 patients spontaneously cleared HCV. The median duration of infection was 17 years. Among patients chronically infected with HCV, an enlarged liver and/or spleen on ultrasound was present in 59%, whereas 63% had abnormal aminotransferases and/or gamma-GT values. In conclusion, 39% of the patients infected in childhood cleared HCV spontaneously. The majority of the patients with chronic hepatitis C had ultrasound and/or laboratory abnormalities and these findings may be associated with the presence of chronic liver disease.

Adolescent↗

PubMed2001

A study of autoimmune markers in hepatitis C infection.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) infection is associated with several autoimmune markers. Despite HCV being common in India, no information on this aspect is available. This study was undertaken to ascertain the frequency and clinical significance of autoimmune markers like rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and to determine the effect of treatment on these markers. METHODS: Twenty five patients with chronic hepatitis C and 25 healthy controls were studied. Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all other autoantibodies. RESULTS: Eighteen patients (72%) demonstrated autoimmune markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were detected in healthy controls. Sixty per cent of the patients had rheumatological symptoms. Of the seven patients followed up after treatment with alpha interferon, only two exhibited persistence of RF, while symptoms and other markers disappeared. INTERPRETATION & CONCLUSION: Rheumatological symptoms and autoimmune markers are common in HCV infection and are usually overlooked. Patients with unexplained joint pains and/or palpable purpura should be screened for HCV. Further studies are needed to delineate fully the link between infection and autoimmunity.

Adult↗

PubMed1993

The serology of chronic hepatitis B infection revisited.

The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays.

Antibody Formation↗

PubMed2003

Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies of HCV replication and pathogenesis have so far been hampered by the lack of an efficient tissue culture system for propagating HCV in vitro. Although HCV is primarily a hepatotropic virus, an increasing body of evidence suggests that HCV also replicates in extrahepatic tissues in natural infection. In this study, we established a B-cell line (SB) from an HCV-infected non-Hodgkin's B-cell lymphoma. HCV RNA and proteins were detectable by RNase protection assay and immunoblotting. The cell line continuously produces infectious HCV virions in culture. The virus particles produced from the culture had a buoyant density of 1.13 to 1.15 g/ml in sucrose and could infect primary human hepatocytes, peripheral blood mononuclear cells (PBMCs), and an established B-cell line (Raji cells) in vitro. The virus from SB cells belongs to genotype 2b. Single-stranded conformational polymorphism and sequence analysis of the viral RNA quasispecies indicated that the virus present in SB cells most likely originated from the patient's spleen and had an HCV RNA quasispecies pattern distinct from that in the serum. The virus production from the infected primary hepatocytes showed cyclic variations. In addition, we have succeeded in establishing several Epstein-Barr virus-immortalized B-cell lines from PBMCs of HCV-positive patients. Two of these cell lines are positive for HCV RNA as detected by reverse transcriptase PCR and for the nonstructural protein NS3 by immunofluorescence staining. These observations unequivocally establish that HCV infects B cells in vivo and in vitro. HCV-infected cell lines show significantly enhanced apoptosis. These B-cell lines provide a reproducible cell culture system for studying the complete replication cycle and biology of HCV infections.

Amino Acid Sequence↗

PubMed2005

Complete genome sequence and phylogenetic analysis of hepatitis B virus isolated from Turkish patients with chronic HBV infection.

Hepatitis viruses are the leading causes of chronic liver disease resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world and also in Turkey. Although Turkey has an intermediate rate of hepatitis B virus (HBV) infection with a prevalence reported as 5%, a complete HBV genome sequence has not been published. In this study, the molecular characterization and phylogenetic analysis are described of 11 complete HBV genomes isolated from 11 naïve patients (5 male, 6 female; ages: 18--54 years old, median 35 years old) with chronic HBV infection. Of 11 patients, 7 and 4 were HBeAg positive/anti-HBe negative and HBeAg negative/anti-HBe positive, respectively. All patients had no co-infection with HCV, HDV, or HIV. HBV DNA was extracted from the sera of the patients. The complete genome was amplified by PCR and cloned into a TA vector. The PCR products were sequenced directly and the complete HBV genome sequences were determined. Ten HBV genomes were 3182 base pairs in length. There was a 183 bp deletion (between nucleotides 2987--3169) in pre-S region in one HBeAg positive patient. There were two pre-core stop codons (G1896A) in two HBeAg negative and three core promoter dual mutations (T1762/A1764) in one HBeAg positive and two HBeAg negative patients' HBV genomes. Phylogenetic analysis of all complete genomes yielded that all Turkish sequences were clustered in genotype D branch (ten in subgenotype D1 and one in subgenotype D2). The analysis of S gene amino acid sequences revealed that surface gene subtypes of one and ten HBV strains were subtype ayw3 and ayw2, respectively. This study indicates that Turkish patients with chronic hepatitis B infection show very little genotypic heterogeneity. Genotype D of HBV DNA and subtype ayw2 of surface gene represent almost the whole Turkish patient population infected with HBV.

Adult↗

PubMed1995

Hepatitis E virus infection in acute hepatitis in Spain.

In order to study the prevalence of hepatitis E virus (HEV) infection in developed countries, IgG and IgM anti-HEV were determined in serum samples from 382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and/or D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected and confirmed by a synthetic peptide-based EIA in 5 (5.6%) non-A, non-B, non-C acute hepatitis, in 3 (6.5%) B and D acute hepatitis, in 10 (4%) acute A hepatitis, in 3 (5.5%) of 54 healthy adults in none of the hemophiliacs and in 3 (6%) patients on hemodialysis. IgM anti-HEV antibodies were only detected in two cases of acute hepatitis B and/or D. Analysis of serial serum samples demonstrated IgG anti-HEV seroconversion in 3 of the 18 confirmed cases; one of them was also positive for IgM anti-HEV. All 3 acute anti-HEV-positive hepatitis cases occurred in adults, were community-acquired (two of them were intravenous drug addicts) and had a self-limited course. These results demonstrate that HEV is a minor cause of acute hepatitis in Spain. A similar low rate of IgG anti-HEV antibodies was detected in patients with different diseases, suggesting that HEV has a very low epidemiological impact. An apparent association of HEV infection with hepatitis B and D suggests a possible parenteral transmission of a mainly enteral pathogen.

Acute Disease↗

PubMed2000

Serum cytokine values and fatigue in chronic hepatitis C infection.

Patients with chronic hepatitis C infection often experience fatigue. In many clinical situations, an association between fatigue and altered serum cytokine levels has been found. Altered cytokine levels in patients with hepatitis C have not shown a correlation with the degree of serum transaminase elevation or pathological change on liver biopsy. The aim of our study was to examine whether there was an association between abnormal serum cytokine levels and fatigue in patients with compensated chronic hepatitis C. Patients referred to a tertiary care hepatology clinic who were hepatitis C antibody positive and who had elevated alanine aminotransferase (ALT) levels were eligible for entry into the study. A control group was also included. Subjects in both groups who had characteristics other than hepatitis C that were known to alter cytokine values and/or cause fatigue were excluded. Patients completed a validated questionnaire to determine their fatigue severity score (FSS). Bioassays were used to measure interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) levels in early morning serum samples taken from patients and controls. Altered cytokine values were defined as those more than two standard deviations above the mean control value. Data was analysed using SPSS, version 8.01. Of the 78 patients with chronic hepatitis C who participated in the study, 19 (24%), 24 (30%) and 45 (56%) had elevated levels of IL-1, IL-6 and TNF-alpha, respectively, compared with only two (6%) of the control group who had elevation of any of the three cytokines. No correlation was found between the FSS and serum cytokine levels, when analysed singly or in combination, in patients with chronic hepatitis C. Hence, alteration in early morning serum levels of IL-1, IL-6 and TNF-alpha in patients with chronic hepatitis C infection and elevated ALT levels bear no correlation with the symptom of fatigue.

Alanine Transaminase↗

PubMed1981

Delayed development of antibody to hepatitis B surface antigen after symptomatic infection with hepatitis B virus.

During a 2-year period, 38 patients with clinical hepatitis B virus infection were seen at the Public Health Service Alaska Native Hospital in Bethel. This hospital serves an area in southwest Alaska that is hyperendemic for hepatitis B virus. The patients came to the hospital at various times from 15 scattered villages, and 92% were Eskimo. None of the patients had a recent history of hypodermic injection or blood transfusions. Twenty-five patients, all originally positive for hepatitis B surface antigen (HBsAg), were followed for up to 5 years after onset of illness, and 15 were either slow to develop, or never developed, antibody to HBsAg (anti-HBs), although only one patient became a chronic carrier of HBsAg. Six patients had a prolonged "window phase" between the disappearance of HBsAg and the appearance of anti-HBs which lasted for more than 1 year. Three patients had only transient anti-HBs after HBsAg disappeared, and five never developed measurable anti-HBs at all. All patients had antibody to hepatitis B core when both HBsAg and anti-HBs were absent. In contrast to studies in other populations, only 42% had anti-HBs 1 year after onset of illness, 63% had it at 18 months, 70% had it at 2 years, and 80% had it at 5 years. Factors related to ethnicity might account for the differences in the development of anti-HBs after acute symptomatic hepatitis B virus infection seen in Eskimos when compared with whites.

Adolescent↗

PubMed1995

Ribavirin therapy for hepatitis C infection following liver transplantation.

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.

Female↗

PubMed1981

The prevalence of hepatitis B infection amongst urban and rural populations in Western Samoa.

A group of 240 urban and 200 rural dwellers in Western Samoa over the age of 20 years was studied for serological evidence of current or past infection with hepatitis B virus (HBV). Overall, 5.5% of subjects were found to be currently infected with HBV and a further 74.5% showed detectable levels of antibody. Antibody to the hepatitis B core antigen was found to be a better marker of past infection than antibody to the surface antigen of the virus. Both the infection rate and carrier rate were higher in males than females and subjects living in rural areas were more likely to be infected than those living in urban areas.

Adult↗

PubMed1999

Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial.

BACKGROUND: Hepatitis A vaccination stops outbreaks of hepatitis A infection, but its efficacy against infection after exposure has not been proven. We investigated the use of hepatitis A vaccine to prevent secondary infections with hepatitis A virus (HAV). METHODS: We did a randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection (index cases). Households (index cases and contacts) were randomly assigned to the vaccine group or unvaccinated group, according to the study week in which they were enrolled. All household contacts in the vaccine group received vaccination at the time of entry to the study. FINDINGS: During 45 days of follow-up, secondary infection had occurred in ten (13.3%) of 75 households (two families had two cases each) in the untreated group and in two (2.8%) of 71 households in the vaccine group. The protective efficacy of the vaccine was 79% (95% CI 7-95). The number of secondary infections among household contacts was 12 (5.8%) of 207 in the unvaccinated group and two (1.0%) of 197 in the vaccinated group. Therefore, 18 individuals needed to be vaccinated to prevent one secondary infection. INTERPRETATION: Hepatitis A vaccine is effective in the prevention of secondary infection of HAV and should be recommended for household contacts of primary cases of HAV infection.

Acute Disease↗

PubMed2003

Prevalence of hepatitis viral infection in dental patients with impacted teeth or jaw deformities.

OBJECTIVE: The prevalence of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis G virus (HGV), and transfusion-transmitted viruses (TTV) was evaluated in patients with impacted teeth or jaw deformities. STUDY DESIGN: Of 486 patients, 268 had serum samples available for retrospective TTV DNA and HGV RNA assays. In addition, the sera of 404 patients were assayed for HB surface antigen and the sera of 340 were assayed for HCV antibody. RESULTS: HGV RNA was detected in 3 of 268 patients (1.1%), and TTV DNA was detected in 60 of 268 (22.4%). Of 404 patients, 3 had HB surface antigens (0.7%). Furthermore, 13 of 340 were HCV-seropositive (3.8%). The rate of infection was similar between patients with impacted teeth and those with jaw deformities, respectively, as follows: 1.1% versus 0%, respectively, for HBV prevalence; 4.1% versus 3.2% for HCV prevalence; 1.8% versus 0% for HGV prevalence; and 22.9% versus 21.4% for TTV prevalence. CONCLUSIONS: Universal precautions to prevent hepatitis and TTV infection during oral surgical procedures are important.

Adult↗

PubMed1995

Correlation of in vivo infectivity of hepatitis C virus to in vitro infectivity and to virion properties.

Serum from an individual who was chronically infected with hepatitis C virus (HCV) was inoculated into chimpanzees and a human T cell line. The serum contained a quasispecies population of HCV consisting of at least six genetic sequences. However, only two sequences (the same two sequences) were recovered both in chimpanzees and in cultured human T cell line, indicating that infection of the culture system reflects infection in vivo.

Amino Acid Sequence↗

PubMed1996

Hepatitis A infection in aircrews: risk of infection and cost-benefit analysis of hepatitis A vaccination.

BACKGROUND: Since a hepatitis A vaccine (HAV) with long-lasting efficacy has become available, its indication in airline crews needs to be determined. HYPOTHESIS: Destinations in developing countries are a risk factor for hepatitis A infection in airline crews, and vaccination is cost-beneficial. METHODS: Retrospective analysis was performed for all Swissair medical files for the period 1987-91. Denominator and cost data were obtained by the personnel department, and a cross-sectional seroepidemiological survey was performed in 734 Sabena staff. RESULTS: Among 3,322 Swissair crewmembers who spent an average of 45 nights in developing countries, 22 hepatitis A infections occurred. For the non-immune crewmembers, the overall annual incidence rate was 1.53 per 1000, whereas the incidence rate while staying in a high risk country was 12.2 per 1000. Cockpit crews with destinations limited to Europe had a rate of zero. Male flight attendants had a threefold higher rate as compared to female flight attendants or pilots. In Sabena, anti-HAV seroprevalence was 33.3%. Increased rates were observed in male as compared to female flying crews and in employees stationed abroad, whereas flying personnel had no higher rate than ground personnel. Simplified comparison of cost of infection and cost of vaccination indicates that vaccination may be cost-saving to the airline company for both male flight-attendants and pilots. CONCLUSIONS: Hepatitis A vaccination may be recommended to staff stationed in high risk countries and to flying crews with such destinations.

Adult↗

PubMedDate not supplied

Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs.

Of 1,801 Chinese subjects, age 1 to 90 years, screened for hepatitis B surface antigen and antibody (HBsAg, anti-HBs) and antibody to hepatitis B core antigen (anti-HBc), 214 (11.9%) had an isolated, positive anti-HBc result; anti-HBc was reproducibly present in the initial sera in only 66% and persisted after an interval of 2 weeks to 3 months in only 73%. There was a strong correlation between the rates of reproducibility and persistence of isolated anti-HBc and the initial anti-HBc titers. Thirty-two subjects with persistent, isolated anti-HBc received four doses of hepatitis B vaccine (5 micrograms, HEVAC B) at 0, 1, 2 and 12 months: 56% developed a primary anti-HBs response in response to hepatitis B vaccine, 16% developed an anamnestic or secondary anti-HBs response, and 28% were undetectable for anti-HBs even after four doses of vaccine. The low rates of reproducibility and persistence of anti-HBc together with the high rate of primary anti-HBs response to hepatitis B vaccine in subjects with isolated anti-HBc raise doubts as to the reliability of anti-HBc (Corzyme, Abbott Laboratories, North Chicago, Ill.) as a single screening test for hepatitis B infection prior to vaccination and suggests that subjects with isolated anti-HBc, in particular those with low anti-HBc titers, be included in vaccination programs.

Adolescent↗

PubMed1993

Progress on the control of hepatitis B infection through immunisation.

Hepatitis B virus (HBV) infection and its sequelae, one of the major diseases of mankind, is now a disease preventable by vaccine. During the last few years, the price of these vaccines has fallen to the point where widespread use in infant immunisation programmes is feasible. This paper reports the great progress that has been made in the control of HBV infection and describes the targets that must be met if HBV control on a global basis is to be achieved.

Cost-Benefit Analysis↗

PubMed1991

[Incidence of so-called hepatic failure syndrome in relation to infection with hepatitis B virus (HBV) in epidemiological and environmental studies of the rural population in the Suwałki and Białystok regions 1978-1990].

In years 1979-1991 has been analysed the selected health epidemiological indices is related with liver pathology and viral hepatitis B infections in rural population of Białystok region. In 11,086 analysed persons of an agricultural sector the frequency of antigenemia HBs (0.25-2.5%) was higher that in control groups of urban populations (0.3-0.6%). In 12 years time period observation of chronic hepatopathy syndrome, demonstrated the increased tendency with parallel pathologic increased values of serum A1AT activity and with increased tendency of HBs antigenemia.

Adolescent↗