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PubMed1985

Factors influencing postexposure immunoprophylaxis of hepatitis B virus infection with hepatitis B immune globulin. High deoxyribonucleic acid polymerase activity in the inocula of unsuccessful cases.

Hepatitis B immune globulin was given intramuscularly to 102 staff members of a dialysis unit within 48 h after the accidental needlestick exposure to blood containing hepatitis B surface antigen (HBsAg). Hepatitis B virus (HBV) infection developed in 11 of 56 persons (20%) who had been exposed to blood containing hepatitis B e antigen (HBeAg). Among 56 HBeAg-positive inocula, HBsAg-associated deoxyribonucleic acid polymerase activity in the 11 inocula that transmitted HBV infection was significantly higher than that in the remaining 45 inocula that did not (log counts per minute 3.27 +/- 0.57 vs. 2.09 +/- 1.19, p less than 0.001). These 11 HBeAg-positive inocula revealed higher hemagglutination titers of HBsAg (geometric mean 13.5 +/- 1.4 vs. 11.2 +/- 3.2, p less than 0.001). The receptor for polymerized human serum albumin was detected significantly more often in the inocula that transmitted HBV infection than those that did not (10/11 vs. 24/45, p less than 0.05). Based on the results obtained, the failure in protecting all of those exposed to HBeAg-positive blood would be attributable to a high concentration of HBV in some HBeAg-positive inocula and the inability of intramuscular injection to raise a protective level of antibody in the circulation immediately.

DNA-Directed DNA Polymerase↗
PubMed2004

Hepatitis B virus infection: co-infection with hepatitis C virus, hepatitis D virus, and human immunodeficiency virus.

Hepatitis B virus (HBV) shares routes of transmission, namely exchange of infected body fluids, sharing of contaminated needles, and blood transfusion, with other hepatotropic viruses, such as hepatitis C virus (HCV) and hepatitis D virus (HDV) and with systemic retroviral infections, such as the human immunodeficiency virus (HIV). Thus, many HBV infected patients are co-infected with other viral pathogens. Co-infection appears to increase the risk of progression of liver disease and may have important ramifications on choice of antiviral medication and treatment regimen. This article reviews the current knowledge of co-infection of HBV with HCV, HDV, and HIV.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.

BACKGROUND: Liver transplantation from hepatitis B core-antibody (HBcAb)-positive donors to hepatitis B surface-antigen (HBsAg)-negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long-term lamivudine monotherapy to prevent development of HBV infection in HBsAg-negative recipients of liver allografts from HBcAb-positive donors. METHODS: From 315 cadaveric adult liver transplantations performed at our unit between July 1999 and March 2005, 18 recipients (5.7%) received liver allografts from HBcAb-positive donors, 13 of whom were HBsAg-negative pre-transplantation. The recipients consisted of four females and 14 males, age range 28-65 yr (median 49.5 yr). Post-transplantation, HBsAg-negative recipients were administered lamivudine 100 mg daily long term. HBsAg-positive recipients were administered low-dose hepatitis B immunoglobulin (HBIg) and lamivudine according to our usual protocol. Standard post-transplantation immunosuppression was given. Recipients were followed up regularly (range 2-69 months, median 21 months) for development of de novo HBV infection. RESULTS: Ten HBsAg-negative recipients received long-term lamivudine. One patient (HBcAb and HBsAb positive pre-transplant) did not receive lamivudine and, in two patients, lamivudine was discontinued following urgent re-transplantation for primary graft non-function. All 13 of the HBsAg-negative recipients were still alive, with no evidence of HBV infection at the end of follow-up. CONCLUSION: Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients from HBcAb-positive donors.

Adult↗
PubMed1991

High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection.

Two hundred eleven HIV-seropositive patients with AIDS, AIDS-related complex, or a CD4+ cell count less than 200 x 10(6) were examined for the presence of hepatitis B virus markers during the course of their HIV infection (median follow-up of 18 months; range of 1 to 107 months). Anti-HBs was detected initially in 138 patients (65%). Sixteen patients (8%) were HBsAg positive at entry. Fourteen had chronic HBV infection of whom 12 initially were positive for HBeAg and HBV DNA; 11 remained positive during follow-up, whereas one seroconverted to anti-HBe and lost HBV DNA. Two patients with chronic HBV infection were initially negative for HBeAg and HBV DNA: one later had reactivated HBV replication and one cleared HBeAg following onset of hepatitis D infection. The last two HBsAg-positive patients had resolving acute HBV infection. Six of the 57 patients who initially were negative for HBV markers acquired HBV infection during follow-up. Four of these six patients developed chronic infection whereas two patients had acute subclinical resolving hepatitis. In addition, four patients became HBsAg positive with their last serum samples, possibly indicating reactivation of HBV infection following progressive immunological and clinical deterioration. None of the patients developed clinical symptoms that could be ascribed to HBV infection, and transaminase elevations were only sporadically recorded. It is concluded that acquisition of HBV infections is not infrequent in HIV-seropositive patients with immune deficiency. Furthermore, the course of both previously established chronic HBV infection and newly acquired HBV infection is modified in such patients, whereas reactivation of past HBV infection seems to be a rare event.

Adult↗
PubMed1995

[Significance of genotypes in chronic hepatitis C virus infection and hepatitis C virus induced liver cirrhosis in Germany].

INTRODUCTION AND OBJECTIVE: Hepatitis C virus (HCV) infection is characterized by a high chronicity rate. Several HCV genotypes have been described. As their distribution pattern in Germany had been unknown it was the aim of this study to determine it in a sizeable group of patients and to find out whether the genotypes differ in the severity of the disease caused by them. PATIENTS AND METHODS: 115 consecutive patients were studied prospectively, 62 (40 men, 22 women) with chronic HCV infection (group 1) and 53 (36 men, 17 women) with liver cirrhosis caused by HCV (group 2). The genotypes were determined by line probe assay. RESULTS: The mean age of the patients in group 1 was significantly lower than that in group 2 (40.4 +/- 13.7 vs 57.1 +/- 12.1 years; P < 0.0001). In group 1, genotype 1b was most frequent (53%; 1a: 21%, 3a: 21%, 2b: 3%, 2a: 2%). Genotype 1b also predominated in group 2 (78%; 1a: 17%, 2a: 4%, 3a: 2%). The differences in frequency between the two groups were significant regarding genotypes 1b (P = 0.01) and 3a (P = 0.005). Genotype 3a was found only in the younger patients. Mean age of patients with genotype 3a and chronic hepatitis C was significantly lower than that of the other patients in this group (34.2 +/- 4.6 vs 42.0 +/- 14.8 years; P < 0.002). CONCLUSIONS: The results show that in Germany genotype 1b predominates and seems to be associated more often with the advanced stages of liver disease. The fact that genotype 3a occurs exclusively in younger patients points to a change in genotype spectrum: infection with this genotype may take a less aggressive course since fewer cases of liver cirrhosis have been observed.

Adult↗
PubMed1997

Incidence of hepatitis C infection in a hepatitis C endemic township in southern Taiwan.

To realize the incidence of hepatitis C virus (HCV) infection in an HCV endemic township, Tzukuan, in Taiwan, we conducted a follow-up community-based survey. A total of 173 adults, 82 males and 91 females, with mean age of 55.5 +/- 9.9 years received initial and follow-up anti-HCV tests with one-year interval. One (1.2%, 95% CI: 0%-5.5%) of 84 anti-HCV-positive subjects was negative-seroconversion, and 4 (4.5%, 95% CI: 0.2%-8.8%) of 89 anti-HCV-negative subjects were positive-seroconversion. The results indicated that hepatitis C might be still spreading in the HCV-endemic area now.

Adult↗
PubMed2004

High prevalence of mixed genotype infections in hepatitis B virus infected intravenous drug users.

The clinical relevance of hepatitis B virus (HBV) genotypes has been documented; however, the prevalence of mixed HBV genotype infections in at-risk groups remains controversial. The HBV genotypes were determined in 325 HBV-infected intravenous drug users (IVDU) who were at a greater risk of multiple exposures to different HBV genotypes by using a newly developed line probe assay. The distribution of HBV genotype was as follows: genotype A alone in 2 (0.6%); genotype B alone in 256 (78.8%); genotype C alone in 10 (3.1%); mixed genotype A and B in 18 (5.5%); genotype B and C in 30 (9.2%); genotype B and D in 1 (0.3%); genotype A and C in 1 (0.3%); and mixed infections of genotype A, B, and C in 3 (0.9%). Clonal analysis confirmed further the existence of mixed genotype infection and recombination between different genotypes. Compared with our previous data, the line probe assay seemed more sensitive than polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in identifying HBV genotype (98.8% vs. 65.0%) and detecting mixed genotype infections (16.3% vs. 0%). In conclusion, the prevalence of mixed HBV infections is substantially higher in IVDU in endemic areas, and the line probe assay is a useful method for rapid genotyping of HBV, with particular reference to the detection of mixed genotype infections.

Adult↗
PubMed1995

Two dose regimens of recombinant interferon-alpha-2b in chronic hepatitis C virus infection. Biochemistry, hepatitis C virus RNA, and liver histology as response indices.

BACKGROUND: Recombinant interferon remains the cornerstone of treatment of chronic hepatitis C virus (HCV) infection. Still, evaluation of treatment on the basis of response indicators and long-term effect of the treatment raises several questions. METHODS: Seventy-four patients with chronic HCV infection were randomized to a high (3 MIU, 3/7 days) or low (1 MIU, 3/7 days) dose of recombinant interferon-alpha-2b for 48 weeks after a 4-week course of 3 MIU, 3/7 days. Response to treatment was assessed by means of liver enzymes (transaminases), HCV RNA, and liver histology. RESULTS: The higher maintenance dose was associated with a significantly higher rate of sustained alanine aminotransferase (ALAT) response (45% versus 19%) and with a significantly better chance of becoming HCV RNA-negative during therapy (47% versus 23%). In the high maintenance dose group 14 of the 29 (48%) patients with available HCV RNA data were negative at the 3-month follow-up, compared with 4 of 27 (15%) in the low maintenance dose group. Significantly more patients had improved liver biopsy findings after interferon in the high maintenance dose group (79%) than in the low maintenance dose group (36%). There was a close correlation between ALAT response and HCV RNA response. Of 17 patients who were HCV RNA-negative 3 months after the end of treatment, 10 remained HCV RNA-negative 2-4 years later. CONCLUSION: The study demonstrates a higher response rate as assessed by biochemistry, HCV RNA, and liver histology in the higher dose group.

Adult↗
PubMed1985

Serum hepatitis B virus-DNA in chronic hepatitis B and delta infection.

Hepatitis B-associated delta agent, a defective RNA virus requiring helper functions of hepatitis B virus (HBV), has been shown to interfere with HBV replication. Low titers of serum hepatitis B surface antigen, absence of hepatitis B e antigen, and low levels of stainable hepatitis B core antigen in liver cells usually seen in chronic delta infection are indirect evidences of such an interference. Measurement of serum HBV-DNA by hybridization with phosphorus 32-labeled HBV-clone DNA is the most sensitive method currently available to detect HBV replication. Using this method, we found that only two of 13 patients with chronic delta infection showed serum HBV-DNA positivity in comparison with seven of 14 patients who had chronic hepatitis B without delta infection. These two groups were matched for hepatitis B e antigen status and liver histopathology. Thus, we report direct evidence of delta agent interfering with the replication of the helper (HBV) virus.

Chronic Disease↗
PubMed1992

[Clinical significance of N-14 antibody (ELISA) in diagnosis of non-A, non-B liver disease].

In 1987 Chiron Co. in USA and Arima et al. in Japan reported successful isolation of clones coding peptides specific for non-A, non-B hepatitis infection. Hepatitis C virus (HCV) genome reported by the Chiron is supposed to have structural proteins of core, matrix, envelope and non-structural proteins of NS 1-5 from 5' to 3' end. C-100 antibody of which antigen is derived from the NS 3-4 region of the HCV genome is used generally, it is not sufficient to diagnose hepatitis C. On the other hand, the nucleotide and amino acid sequences in the epitope of N-14 clone established by Arima et al. have homology to those of core region of the HCV genome. Usually there are some mutation in sequences of HCV genome, but there is little mutation in 5' non-coding region and core protein area. Therefore we could diagnose hepatitis C more exactly by using N-14 antibody. In the present study N-14 antibody was determined in 871 healthy subjects and 285 cases with liver diseases by an ELISA. 1.6% of healthy subjects and 70-75% of cases with non-A, non-B chronic liver diseases are positive for N-14 antibody. In acute non-A, non-B hepatitis, 33.3% of sporadic cases and 75.0% of post-transfusion cases are positive for the test. As only 2 of 100 cases with other liver diseases are positive for the test, the N-14 antibody test seems to be highly sensitive and specific for the non-A, non-B hepatitis virus infection. These 1156 cases were tested for the C-100 antibody as well. No much difference between the results by using these tests, 15-20% of discrepancy between the tests, has been observed. In conclusion hepatitis C can be diagnosed exactly by using N-14 antibody as well as by C-100 antibody. In addition for more exact diagnosis of hepatitis C, tests by N-14 antibody in combination with C-100 antibody will be prefered to determine anti HCV.

Adolescent↗
PubMedDate not supplied

[Quantitative antibody analysis: use for the diagnosis of hepatitis C virus chronic infection].

Hepatitis C virus (HCV) infection has been estimated in 600,000 subjects in France, with about 80 % of chronic infection. In the latter, anti-HCV antibodies and viral RNA are found together in patients blood. Today, only the use of polymerase chain reaction (PCR) technology allows the diagnosis of HCV chronic infection, confirmed by a positive PCR. However, PCR is a laborious and cost effective method. The aim of this study was to distinguish HCV chronic infection to past-infection or false reactivity only using the serology testing. Therefore, we looked for a correlation between the results of PCR, using the HCV Cobas Amplicor 2.0 assay, and the level of anti-HCV antibodies, assessed by the AxSYM HCV v.3.0 and expressed in signal/cutoff (s/co) ratio. We found using a panel of 200 sera issued from 181 patients, a significant variation of s/co ratios between PCR positive and negative patients (respectively, 87.76 +/- 27.18 vs 10.13 +/- 13.68 s/co, p < 0.0001), only in non treated or previously treated patients, non HIV coinfected, non renal transplanted or haemodialysis patients. An anti-HCV cutoff value at 34 s/co allows a predictive PCR results with 100 % sensitivity and 93.3 % specificity. Thus, for patients having a s/co equal or over 34, a positive PCR was found in 98.1 % of cases, allowing the diagnosis of HCV chronic infection (positive predictive value). Conversely, in patients with less than 34, HCV chronic infection can be excluded in 100 % of cases (negative predictive value). In conclusion, in most cases, the use of anti-HCV quantitative analysis in the AxSYM HCV v.3.0 assay could avoid PCR testing and facilitate the diagnosis of HCV chronic infection.

Adolescent↗
PubMed2002

Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) infection has been found to be strikingly associated with autoimmune phenomena. The aim of the present study was to investigate the presence of various autoantibodies in patients with HCV infection. Anti-neutrophil cytoplamic antibody (ANCA), anti-dihydrolipoamide dehydrogenase (anti-E3), rheumatoid factor (RF), anti-dihydrolipoamide acetyltransferase (anti-E2), anti-SS-A/Ro (60 kD), anti-SS-A/Ro (52 kD), anti-SS-B/La, anti-topoisomerase II (anti-topo II), anti-cardiolipin (aCL), anti-dsDNA, anti-ssDNA, anti-nuclear antibodies (ANA), anti-proteinase 3 (anti-Pr3) and anti-myeloperoxidase (anti-MPO) were determined in sera from 516 patients with HCV infection, 11 with primary biliary cirrhosis (PBC) and 44 healthy controls. Assays employed were indirect immunofluoresence, the particle latex agglutination test, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. ANCA, anti-E3 antibody and RF were positive in 278/516 (55.6%), 276/516 (53.3%) and 288/516 (56%) patients with HCV infection, respectively. Positivity for ANA was present in 15.8%, anti-ssDNA in 15.6%, anti-dsDNA in 8.5%, aCL in 5%, anti-SS-B/La in 4.1%, anti-SS-A/Ro (60 kD) in 3.9%, anti-E2 in 3.3% and anti-SSA/Ro (52 kD) in 1.2%, anti-MPO in 4.8%, anti-Topo II and anti-actinin in 0%. All sera with ANCA showed c-ANCA patterns and contained anti-PR3 specificity. HCV patients with ANCA showed a higher prevalence of skin involvement, anaemia, abnormal liver function and alpha-Fetoprotein (alpha-FP). HCV patients with anti-E3 antibodies showed a higher prevalence of liver cirrhosis, arthritis, abnormal liver function and elevated alpha-FP levels. The prevalence of autoantibodies was not affected by treatment with interferon-alpha (IFN-alpha). In conclusion, autoantibodies are commonly found in patients with HCV infection. There is a high prevalence of anti-E3, ANCA and RF in these patients. Proteinase 3 and E3 are the major target antigens in HCV infection. HCV may be regarded as a possible causative factor in ANCA-related vasculitis.

Autoantibodies↗
PubMed2001

High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology.

BACKGROUND/AIMS: In approximately 5% of chronic liver disease cases, no aetiology can be identified. We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to define potential clinical outcomes. METHODS: Patients' sera were screened with highly sensitive polymerase chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus. Sera were also retested for antibodies against the core antigen of HBV. RESULTS: Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%) patients. Immunostaining for HBV antigens on biopsies from patients positive for HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples. Eleven of the fifteen patients were anti-HBc positive. With one exception, all patients carried HBV genomes at low levels (10(4) copies/ml or less). Histological signs of chronic liver disease were observed in all patients. CONCLUSION: Unrecognised HBV infections may account for a high proportion of chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which appear mandatory for the diagnosis and management of non-A non-E hepatitis as well as for improved safety of transfusions and transplantations are needed.

Adult↗
PubMed1995

Serological evidence of past hepatitis B infection in liver donor and hepatitis B infection in liver allograft.

The presence of hepatitis B surface and core antibodies (anti-HBs and anti-HBc) in a liver donor without hepatitis B surface antigen is taken to indicate resolution of hepatitis B and is not considered to contraindicate donation. We report a liver transplant recipient who developed hepatitis B after such a donation. It seems that hepatitis B virus can reside in the liver of a patient who has seemingly recovered from his disease. We recommend avoidance of liver transplants from donors who are positive for anti-HBs and anti-HBc.

Female↗
PubMed1985

Prevention of perinatally transmitted hepatitis B virus infection by hepatitis B immunoglobulin immunoprophylaxis: an account of 201 newborn babies of hepatitis Bs antigen carrier mothers.

Of 5,327 pregnant women who were screened between July 1981 and July 1983, 5.2% were found to be hepatitis Bs antigen (HBsAg) carriers. This high percentage of carriers accentuates the importance of vertical transmission of hepatitis B virus in our area. In view of this we sought to verify the effectiveness of hyperimmune immunoglobulins in the prevention of infection. We studied 201 babies born to HBsAg-positive mothers. These babies had regular checkups until 12 months of age. One hundred forty-nine received prophylactic hyperimmune globulin (two to seven doses according to risk ranking), while 52 did not. A higher percentage of infection was found in the babies who had no prophylaxis (25%) than in the babies who had prophylaxis (7.4%). Furthermore, hepatitis appeared earlier (from the 2nd to the 6th month) in the babies who had no prophylaxis than in the babies who had prophylaxis (from the 9th to the 12th month). No infection was observed during prophylaxis or up to 6 months.

Carrier State↗
PubMed1999

Membranoproliferative glomerulonephritis type I, mixed cryoglobulinemia and lymphoma in the absence of hepatitis C infection.

Chronic hepatitis C virus infection has been linked to cryoglobulinemia, membranoproliferative glomerulonephritis, and malignant B-cell lymphoproliferation, suggesting a possible pathogenetic link between these disorders. We report a patient with the latter clinical triad in the absence of hepatitis C infection. We postulate that the persistent and dysregulated immunologic activity associated with chronic antigen stimulation, inflammation and/or B-cell malignancy induces nephritogenic autoantibodies, including cryoglobulins, that produce a similar clinical syndrome in genetically susceptible individuals.

Biopsy, Needle↗
PubMedDate not supplied

Dane particle-associated hepatitis B e antigen in patients with chronic hepatitis B virus infection and hepatitis B e antibody.

A commercial radioimmunoassay was adapted to detect serum Dane particle-associated HBeAg in patients whose sera contained homologous antibody. HBeAg was released from Dane particles with guanidine HCl. Dane particles were separated from anti-HBe by gel-filtration (Sepharose 4B) and ultracentrifugation of the eluate. Dane particle-HBeAg was tested in 45 HBsAg carriers with anti-HBe and was present in 8 (18%) carriers, all of whom had chronic liver disease. By contrast, HBeAg was not found in 10 carriers with normal liver histology. Serum or liver HBcAg was found in 6 of 8 patients with Dane particle-HBeAg. None of the carriers without Dane particle-HBeAg had other markers of hepatitis B virion synthesis. We conclude that Dane particle-HBeAg provides a sensitive index of active hepatitis B virus replication, a guide to the presence of chronic hepatitis in HBsAg carriers with anti-HBe, and a noninvasive method to follow infection in these patients.

Antibodies, Viral↗