Hepatitis B and C coinfection is commonly seen in clinical practice. In coinfected individuals, high levels of hepatitis C viremia are often associated with low levels of serum hepatitis B DNA. Hepatitis B reactivation in hepatitis C-infected patients treated with pegylated interferon and ribavirin has been reported, but severe or fulminant reactivation is uncommon. Hepatitis C treatment-associated hepatitis B reactivation in patients with chronic hepatitis C and isolated core antibody has not been reported previously.
A 59-year-old white woman with chronic hepatitis C genotype 1B and isolated hepatitis B core antibody initiated treatment with simeprevir, sofosbuvir, and ribavirin for treatment of chronic hepatitis C. She responded very well to treatment initially with near normalization of aminotransferases and hepatitis C viral load suppressed to below the level of quantification after 4 weeks of treatment. At week 11 of a planned 12-week course, she developed fulminant hepatic failure due to hepatitis B reactivation and ultimately required liver transplantation. Fortunately, her posttransplant clinical course was unremarkable.
This is the first report of hepatitis B reactivation in a patient with isolated hepatitis B core antibody leading to fulminant hepatic failure and liver transplantation after initiation of treatment with sofosbuvir, simeprevir, and ribavirin for hepatitis C. This case raises the concern for the risk of severe hepatitis B reactivation in hepatitis B and C-coinfected patients or chronic hepatitis C-infected patients with isolated hepatitis B core antibody treated with direct-acting antiviral drugs for hepatitis C.
Hepatitis B; Hepatitis C; Simeprevir; Sofosbuvir; Fulminant liver failure; Liver transplant; Hepatitis B reactivation
Since the introduction of Highly Active Anti-Retroviral Therapy and the dramatic improvement in the prognosis of individuals with Human Immunodeficiency Virus, liver disease due to chronic viral hepatitis has become as important cause of morbidity and mortality in co-infected individuals. The objective of the study was to determine the Sero-prevalence of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus and the association of the virus with Hepatitis B Virus and Hepatitis C Virus infection. As Human Immunodeficiency Virus and Hepatitis B Virus infections are highly prevalent and they are among the major public health concern in developing countries including Ethiopia investigating this problem is of paramount benefit. Although studies on co-infection of Hepatitis C Virus and Human Immunodeficiency Virus have clearly identified adverse effects of co-infection, the prevalence of Hepatitis C Virus infection and the association with Human Immunodeficiency Virus in developing countries including Ethiopia has not been know for sure.
A cross sectional study was conducted from January 1 to 31, 2010, in Jimma University specialized hospital Blood Bank. The inclusion criteria of the study was adult who donated blood to Jimma University specialized hospital blood bank any time from establishment of the unit until January 2010 and whose record was retrieved. Accordingly 9,204 adults were included of which 6,063 were selected by lottery method. Data on socio-demographic variables (age and sex), laboratory test result for Hepatitis B surface Antigen, anti-Hepatitis C Virus antibody, anti-Human Immunodeficiency Virus 1 antibody, and Rapid Plasma Reagin tests were collected using structured questionnaire. After the data were collected, they were entered into a computer and analyzed using SPSS -16 for windows. P-Value of < 0.05 was taken to be statistically significant.
The prevalence rate of Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus and syphilis infection were 2.1%, 0.2%, 2.1% and 0.7%, respectively. Sex and age had statistically significant association with Human Immunodeficiency and Hepatitis B virus infections where females were less likely to be infected. As age increases above 20 years, the risk of infection with Human Immunodeficiency Virus or Hepatitis B Virus increases. There was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus.
the prevalence rate of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus infections among blood donors in Jimma University specialized hospital were lower as compared to previous studies, in addition there was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus. Thus, community based study should be conducted to confirm the relationship of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus.
Hepatitis B; Hepatitis C; HIV; blood donors; Southwest Ethiopia
OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.
The understanding of the distribution of hepatitis B virus genotypes and the occult hepatitis B virus infection in hepatocellular carcinoma may shed light into the prevention and treatment of hepatocellular carcinoma. The purpose of the study is to investigate hepatitis B virus genotypes distribution, the high-risk genotypes and the occult infection in north-western China's hepatocellular carcinoma patients.
Hepatitis B virus genotypes A-D of hepatocellular carcinoma tumor tissues and serum samples in 268 north-western China hepatocellular carcinoma patients were detected by fluorescence polarization assay. The hepatitis B virus genotypes in serum and matched primary tumor tissue samples were compared. Hepatitis B surface antigen and α-fetoprotein in serum were detected. Occult hepatitis B virus infections were analyzed. The relationship between hepatitis B virus genotypes and clinicopathologic characteristics were analyzed statistically using SPSS v.10.0.
Intrahepatic hepatitis B virus DNA was detected in 83.6% of 268 patients, whereas serum hepatitis B virus DNA was detected in 78.7%. The hepatitis B virus genotypes in serum were consistent with the results in matched tumor tissue. Intrahepatic hepatitis B virus genotype B and C were detected respectively in 11.6% and 54.5% of the patients. Mixed intrahepatic hepatitis B virus genotypes were detected in 13.4% of 268 patients. There was not mixed hepatitis B virus infection in Edmondonson grade I. The patients with mixed HBV genotypes exhibited statistically significant different Edmondson grade than the patients with single type HBV infection (p < 0.05). Hepatitis B surface antigens were positive in 77.2% of 268 patients. Hepatitis B virus genotype C was detected in 64.7% of occult infected patients. There was no significant differences of patients' ages and α-fetoprotein level in different groups of intrahepatic hepatitis B virus genotypes (p > 0.05).
Hepatitis B virus genotype C was associated closely with the development of hepatocellular carcinoma and the occult hepatitis B virus infection in patients in north-western China. There was a relatively high prevalence of mixed hepatitis B virus infection in Edmondonson grade III-IV.
hepatitis B virus genotype; hepatocellular carcinoma; fluorescence polarization; north-western China
Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content.
RESEARCH DESIGN AND METHODS
Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%.
Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = −0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = −0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = −0.329, P = 0.004).
In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology.
Background: Endoplasmic reticulum (ER) stress has been implicated in causing hepatic insulin resistance.
Results: Fructose-fed XBP1 knock-out mice were protected from hepatic insulin resistance despite increased hepatic ER stress and JNK activation.
Conclusion: ER stress and hepatic JNK activation can be disassociated from hepatic insulin resistance.
Significance: Hepatic ER stress is not a direct causal factor in hepatic insulin resistance.
Hepatic insulin resistance has been attributed to both increased endoplasmic reticulum (ER) stress and accumulation of intracellular lipids, specifically diacylglycerol (DAG). The ER stress response protein, X-box-binding protein-1 (XBP1), was recently shown to regulate hepatic lipogenesis, suggesting that hepatic insulin resistance in models of ER stress may result from defective lipid storage, as opposed to ER-specific stress signals. Studies were designed to dissociate liver lipid accumulation and activation of ER stress signaling pathways, which would allow us to delineate the individual contributions of ER stress and hepatic lipid content to the pathogenesis of hepatic insulin resistance. Conditional XBP1 knock-out (XBP1Δ) and control mice were fed fructose chow for 1 week. Determinants of whole-body energy balance, weight, and composition were determined. Hepatic lipids including triglyceride, DAGs, and ceramide were measured, alongside markers of ER stress. Whole-body and tissue-specific insulin sensitivity were determined by hyperinsulinemic-euglycemic clamp studies. Hepatic ER stress signaling was increased in fructose chow-fed XBP1Δ mice as reflected by increased phosphorylated eIF2α, HSPA5 mRNA, and a 2-fold increase in hepatic JNK activity. Despite JNK activation, XBP1Δ displayed increased hepatic insulin sensitivity during hyperinsulinemic-euglycemic clamp studies, which was associated with increased insulin-stimulated IRS2 tyrosine phosphorylation, reduced hepatic DAG content, and reduced PKCϵ activity. These studies demonstrate that ER stress and IRE1α-mediated JNK activation can be disassociated from hepatic insulin resistance and support the hypothesis that hepatic insulin resistance in models of ER stress may be secondary to ER stress modulation of hepatic lipogenesis.
Ceramide; Diacylglycerol; ER Stress; Gluconeogenesis; Glucose Metabolism; Insulin Resistance; Lipid Metabolism; Liver Metabolism; Protein Kinase C (PKC)
BACKGROUND/AIMS—The role of hepatitis C virus (HCV) in fulminant hepatitis remains controversial. This study was conducted to investigate the risk of fulminant hepatitis C in relation to HCV genotypes and concurrent infection of other viruses.
PATIENTS—109 HCV RNA positive patients from 334 consecutive cases hospitalised to a medical centre in northern Taiwan for overt acute viral hepatitis were prospectively evaluated.
METHODS—HCV RNA was detected by a combined reverse transcription-polymerase chain reaction assay. HCV genotypes were analysed using a genotype specific probe based assay in the 5' untranslated region.
RESULTS—39 patients tested positive for hepatitis B surface antigen but negative for IgM antibody to hepatitis B core antigen, indicating concurrent chronic hepatitis B virus (HBV) infection. Twelve patients were hepatitis G virus (HGV) RNA positive. Genotyping of HCV disclosed 1b in 93, 1b mixed with 2a/2c or 1b mixed with 2b in 11, and not classified in five. Serum titres of HCV RNA were <105 copies/ml in 77, 105-107 copies/ml in 25, and >107 copies/ml in seven. Eleven patients (10.1%) had fulminant hepatitis as a complication. Development of fulminant hepatitis did not correlate with age and gender of the patients, concurrent HGV infection, HCV genotypes, or serum titre of HCV RNA. However, the incidence (95% confidence interval) of fulminant hepatitis in patients with underlying chronic HBV infection was 23.1% (9.9 to 36.3%), which is significantly higher than in those without (2.9% (−1.0 to 6.8%)). In 39 patients with concurrent chronic HBV infection, the clinical and virological characteristics showed no significant difference between those with fulminant hepatitis and those without.
CONCLUSIONS—Acute hepatitis C in patients with concurrent chronic HBV infection is associated with a substantial risk of fulminant hepatitis.
Keywords: acute hepatitis C; fulminant hepatitis; hepatitis B virus; hepatitis C virus; hepatitis G virus
Recent reports suggest an increase in sexually-transmitted hepatitis C infection among HIV-infected men who have sex with men (MSM) in European cities. We investigated whether current national surveillance systems in England and Wales (E&W) are able to monitor sexual transmission of hepatitis C infection among HIV-infected MSM.
Routine laboratory reports of hepatitis C diagnoses and data from sentinel hepatitis C testing surveillance were matched to HIV diagnosis reports to determine: (i) the number of MSM diagnosed with HIV and hepatitis C (1996–2003); (ii) the number of HIV-diagnosed MSM tested for hepatitis C and found to be positive at sentinel sites (2003).
(i) Between 1996–2003, 38,027 hepatitis C diagnoses were reported; 25,938 (68%) were eligible for matching with HIV diagnoses. Thirty-one men (four in London) had both a HIV and hepatitis C diagnosis where the only risk was sex with another man. Numbers of "co-diagnosed" MSM increased from 0 in 1996 to 14 in 2003. The majority of MSM (22/31) tested hepatitis C positive after HIV diagnosis. (ii) Of 78,058 test results from sentinel hepatitis C testing sites in 2003, 67,712 (87%) were eligible for matching with HIV diagnoses. We identified 242 HIV-diagnosed MSM who did not inject drugs who tested for hepatitis C in 2003; 11 (4.5%) tested hepatitis C positive (95%CI: 2.3%–8.0%). Applying this percentage to all MSM seen for HIV-related care in E&W in 2003, an estimated 680 MSM living with diagnosed HIV would have tested positive for sexually-transmitted hepatitis C (95%CI: 346–1208).
Matching routine laboratory reports of hepatitis C diagnoses with HIV diagnoses only identified 31 HIV infected MSM with sexually-transmitted hepatitis C infection. Clinical studies suggest that this is an underestimate. On the other hand, matching sentinel surveillance reports with HIV diagnoses revealed that in E&W in 2003 nearly 5% of HIV-diagnosed MSM tested hepatitis C positive where the only risk was sex with another man. Reports of sexually-transmitted hepatitis C infection were not confined to London. Enhanced surveillance is needed to monitor sexually-transmitted hepatitis C among HIV-infected MSM in E&W.
Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.
Viral hepatitis may be classified into three or more forms including type A hepatitis, type B hepatitis, and a group denoted as non-A non-B hepatitis which may represent viral hepatitis of one or more causes. The differentiation of these forms of hepatitis is primarily serologic. The development of antibody to hepatitis A virus can be detected by radioimmunoassay as well as by other test systems. The serologic diagnosis of type B hepatitis rests on the detection of hepatitis B surface antigen or on the development of antibody to hepatitis B core antigen or hepatitis B surface antigen. The serologic diagnosis of non-A non-B hepatitis is a diagnosis of exclusion for assay systems for this form of disease are not yet available.
A prototype hepatitis B vaccine has been prepared and is currently undergoing clinical trials. Gamma globulin is now available that contains high titered antibody against hepatitis B virus. Normal immune globulin contains high titers directed against hepatitis A virus. Therefore, for documented exposure, effective prophylaxis is available for both of these forms of acute liver disease. The past decade has resulted in rapid advances in our understanding of the pathogenesis of acute hepatitis and its extrahepatic manifestations. However, it is clear that specific treatment for acute hepatitis and the accurate description of the etiologic agents of non-A non-B hepatitis require exploration.
Objective To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen.
Design Systematic review and meta-analysis of randomised clinical trials.
Data sources Electronic databases and hand searches.
Review methods Randomised clinical trials were assessed for methodological quality. Meta-analysis was undertaken on three outcomes: the relative risks of hepatitis B occurrence, antibody levels to hepatitis B surface antigen, and adverse events.
Results 29 randomised clinical trials were identified, five of which were considered high quality. Only three trials reported inclusion of mothers negative for hepatitis B e antigen. Compared with placebo or no intervention, vaccination reduced the occurrence of hepatitis B (relative risk 0.28, 95% confidence interval 0.20 to 0.40; four trials). No significant difference in hepatitis B occurrence was found between recombinant vaccine and plasma derived vaccine (1.00, 0.71 to 1.42; four trials) and between high dose versus low dose vaccine (plasma derived vaccine 0.97, 0.55 to 1.68, three trials; recombinant vaccine 0.78, 0.31 to 1.94, one trial). Compared with placebo or no intervention, hepatitis B immunoglobulin or the combination of plasma derived vaccine and hepatitis B immunoglobulin reduced hepatitis B occurrence (immunoglobulin 0.50, 0.41 to 0.60, one trial; vaccine and immunoglobulin 0.08, 0.03 to 0.17, three trials). Compared with vaccine alone, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (0.54, 0.41 to 0.73; 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported adverse events.
Conclusion Hepatitis B vaccine, hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B occurrence in newborn infants of mothers positive for hepatitis B surface antigen.
There is evidence that patients suffering from chronic hepatic diseases, including chronic hepatitis B and chronic hepatitis C, have a reduced health-related quality of life. The aim of this study was to evaluate the impact of the notification of test results for hepatitis B and hepatitis C on the quality of life of blood donors.
Over a 29-month period, this study assessed the quality of life of 105 blood donors with positive serological screening tests for hepatitis B and hepatitis C and donors who presented false-positive test results. The Medical Outcome Study 36-Item Short Form Health Survey Questionnaire was applied at three time points: (1) when an additional blood sample was collected for confirmatory tests; (2) when donors were notified about their serological status; and (3) when donors, positive for hepatitis B and hepatitis C, started clinical follow-up. Quality of life scores for the confirmed hepatitis B and hepatitis C groups were compared to the false-positive control group.
The domains bodily pain, general health perception, social function, and mental health and the physical component improved significantly in donors with hepatitis C from Time Point 1 to Time Point 3. Health-related quality of life scores of donors diagnosed with hepatitis B and hepatitis C were significantly lower in six and four of the eight domains, respectively, compared to the false-positive control group.
A decreased quality of life was detected before and after diagnosis in blood donors with hepatitis B and hepatitis C. Contrary to hepatitis B positive donors, the possibility of medical care may have improved the quality of life among hepatitis C positive donors.
Hepatitis B; Hepatitis C; Quality of life
The uptake of 125I albumin microaggregates (U-125I-AMA) from portal blood, during a single passage through the hepatic reticuloendothelial system, has been found to be generally decreased in cirrhosis. To investigate if a similar phenomenon occurs for the colloid flowing through the hepatic artery, the U-125I-AMA was first calculated in normal dogs after injection of a mixture of 51Cr red blood cells (51Cr-RBC) and 125I-AMA into the hepatic artery by comparing hepatic indicator dilution curves (IDC) obtained with both indicators. In nine dogs, the U-125I-AMA from hepatic artery blood was generally over 90%, as previously reported for the same colloid flowing through the portal vein in another group of normal dogs. This approach was then applied in nine patients with alcoholic cirrhosis who underwent combined umbilicoportal vein, hepatic vein, and hepatic artery catheterisation because of severe portal hypertension. Hepatic indicator dilution curves were obtained in the nine patients after injection of a mixture of 51Cr-RBC and 125I-AMA into the portal vein and the hepatic artery. The U-125I-AMA from portal and hepatic artery blood was measured by comparing 51Cr-RBC and 125I-AMA hepatic IDC. U-125I-AMA varied between 5·2 and 90·5% after portal vein injection and between 13·7 and 90·1% after hepatic artery injection; not difference was found between paired values. In all patients the extraction of indocyanine green (E-ICG) was calculated during a continuous infusion and significant correlations were found between E-ICG and U-125I-AMA from portal blood (r=0·931; p <0·001) or from hepatic artery blood (r=0·861; p <0·005). The decreased uptakes can be related to intrahepatic shunts or sinusoidal changes responsible for ineffective phagocytosis and restricted access of dye to parenchymal cells. These data indicate that in cirrhosis the hepatic artery and portal vein blood is cleared of colloid and ICG in a similar fashion and suggest nearly identical blood supply to the regenerative nodules by the hepatic artery and portal vein. Thus U-125I-AMA from hepatic artery or portal vein blood, as well as the E-ICG, may be used to estimate the functional hepatic blood supply in cirrhosis; this may prove to be useful in the prognosis of patients before portacaval shunts.
Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A.
We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups.
The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers.
While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection.
Hepatitis A; Severity; Liver failure; Fulminant
Objective: This study aimed to explore clinical and virological characteristics of chronic hepatitis B (CHB) patients with hepatic steatosis in order to provide a theoretical basis for the prevention and control of hepatic steatosis.
Methods: A total of 360 CHB inpatients were recruited from Affiliated Dongnan Hospital of Xiamen University and divided into hepatic steatosis group and non- hepatic steatosis group. The body mass index (BMI), waist-to-hip ratio (WHR), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), hepatitis B e antigen (HBeAg), hepatitis B virus DNA (HBV DNA) and hepatic histological changes were detected and compared between the two groups. The association of these factors with hepatic steatosis was evaluated in CHB patients.
Results: BMI, FPG, TG, TC, GGT, AST and HBV DNA showed statistically significant differences between two groups (P<0.01). The patients with hepatic steatosis had markedly higher BMI, FBG, TG and TC than those without steatosis did. No significant differences were found in ALT and HBeAg between two groups (P>0.05). In male patients, there was marked difference in the WHR between two groups (P < 0.01), which was not found in female patients (P > 0.05). The severity of hepatic steatosis increased in patients with hepatic steatosis, compared to those without steatosis (P < 0. 01), but the severities of inflammation and fibrosis in the non-hepatic steatosis group were dramatically higher than those in the hepatic steatosis group (P < 0. 01).
Conclusions: BMI, WHR, FBG, TG and TC appeared to be influencing factors of CHB combined with hepatic steatosis. Hepatic steatosis in CHB patients was closely related to changes in anthropometric indices and metabolic factors but not HBV. It is necessary to improve these factors to effectively prevent hepatic steatosis in CHB patients.
Chronic hepatitis B; Hepatic steatosis; anthropometric index; Metabolic factor.
AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression.
METHODS: Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively.
RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells. HBV DNA replication intermediates were also observed at 72 h after transfection, including relaxed circular DNA, double-stranded DNA and single-stranded DNA. Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles with a spherical or filamentous shape, were detected in the supernatant.
CONCLUSION: SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3-transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell model.
SV40 T-antigen; Mouse hepatic cell; Hepatitis B virus 1.3-fold genome plasmids; Immortalized; Liposomes; Transfection
Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful pharmacotherapy for opioid addiction stabilizes patients and improves patient compliance to care and treatment regimens as well as promotes good patient outcomes. Implementation and integration of effective hepatitis prevention programs, care programs, and treatment regimens in concert with the pharmacological therapy of opioid addiction can reduce the public health burdens of hepatitis and injection drug use.
hepatitis; methadone; substance abuse treatment; medication assisted treatment
1. Hepatic volume was recorded by a plethysmographic technique in cats anaesthetized with pentobarbitone; the hepatic artery and portal vein remained intact. Dose-response curves were obtained for intravenous infusions of adrenaline, noradrenaline, angiotensin, vasopressin and histamine.
2. Adrenaline and noradrenaline decreased hepatic blood volume and did not differ significantly in potency. Up to 40% of the hepatic blood volume was expelled by doses within the range secreted by the adrenal medullae.
3. Isoprenaline, infused into the hepatic artery, had no significant effect on hepatic blood volume in doses which caused maximal vasodilatation of the hepatic arterial bed. Relaxation of hepatic capacitance vessels mediated by β-adrenoceptors did not occur.
4. Angiotensin infusions in doses previously shown to cause intestinal and splenic vasoconstriction, decreased hepatic blood volume and on a molar or microgramme basis, angiotensin was the most potent of the agents tested. Doses within the probable physiological range of endogenous production decreased hepatic blood volume by up to 20%. The responses were not significantly different when the hepatic nerves were intact or sectioned.
5. Vasopressin infusions produced only small decreases in hepatic blood volume. Doses within the range secreted by the posterior pituitary which constrict the intestinal and splenic resistance vessels, did not decrease hepatic blood volume by more than 10%.
6. Histamine produced no change in hepatic blood volume in doses which readily produce outflow block in dogs. Either the specific hepatic venous smooth muscle involved in outflow block is absent in the cat or it has no histamine receptors.
7. After the rapid change in hepatic blood volume at the onset of the infusion, hepatic volume remained steady for the duration of each infusion. There was no evidence that these agents caused net transsinusoidal fluid movements.
The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and emtricitabine) in the prevention of human immunodeficiency virus infection. Because Truvada can suppress hepatitis B virus replication, and withdrawal of Truvada can cause hepatic flares in patients with chronic hepatitis B, pre-enrollment screening included serological screening for hepatitis B virus markers. Women with chronic infections were not enrolled in the trial. Women found to be unprotected against hepatitis B were enrolled and offered three doses of hepatitis B vaccine. Reinfection and reactivation of previously resolved hepatitis B virus infections have been documented in immunosuppressed individuals but not in healthy individuals. We present the case of a participant enrolled in the FEM-PrEP clinical trial with baseline evidence of immunity against hepatitis B virus who subsequently developed acute hepatitis B.
A 21-year-old Black non-pregnant woman was enrolled in the FEM-PrEP trial. She was human immunodeficiency virus-negative and a serological test for hepatitis B virus was negative. She had evidence of low levels of protection against hepatitis B virus and normal liver function. She had no hepatitis B vaccination history, thus it was concluded that she had post-infection immunity. At week 36 she presented with severely elevated liver enzyme levels that, upon further investigation, were a result of acute hepatitis B virus infection. The infection followed an asymptomatic course until full recovery of her liver enzymes a few weeks later. At study unblinding, the participant was found to be on the Truvada arm. Retrospective plasma drug level testing found low levels of study drugs from week 4. The participant remained human immunodeficiency virus-negative throughout the study.
Hepatitis B virus infection reactivation or reinfection is a rare phenomenon in healthy individuals. However, reactivations have been reported in patients being treated for chronic hepatitis B with the drugs contained in Truvada, after treatment had been withdrawn. This participant may have reactivated after stopping Truvada, or she may have reactivated spontaneously owing to relatively low levels of protective antibodies against hepatitis B. Alternatively, she may have been reinfected. Clinicians should be aware that hepatitis B virus reactivation or reinfection may cause elevated transaminases even in the presence of low baseline immunity.
FEM-PrEP; Hepatitis B virus; Reactivation; Reinfection
Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D, as evidenced by the decline of hepatitis D in recent years. Since the presence of hepatitis D is associated with suppressed HBV replication and possibly infectivity, it is reasonable to speculate that hepatitis D may facilitate the control of HBV.
Methodology and Principal Findings
We introduced a mathematical model for the transmission of HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection transmit both viruses. We calculated the reproduction numbers of single HBV infections and dual HBV and hepatitis D infections and examined the endemic prevalences of the two viruses. The results show that hepatitis D virus modulates not only the severity of the HBV epidemic, but also the impact of interventions for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper the eradication of HBV. Interventions that aim to reduce the basic reproduction number of HBV below one may not be sufficient to eradicate the virus, as control of HBV depends also on the reproduction numbers of dual infections.
Conclusions and Significance
For populations where hepatitis D is endemic, plans for control programs ignoring the presence of hepatitis D may underestimate the HBV epidemic and produce overoptimistic results. The current HBV surveillance should be augmented with monitoring of hepatitis D, in order to improve accuracy of the monitoring and the efficacy of control measures.
Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p < 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p < 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.
Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were positive for both serology and serum hepatitis C virus RNA. Serum hepatitis C virus RNA detection occurred five to 33 months before hepatitis C virus antibodies. Liver tissue hepatitis C virus RNA and hepatitis C virus core antigen were detected in five. In one patient, tissue hepatitis C virus core antigen was detected when other tests for hepatitis C were negative. Two patients had positive human cytomegalovirus serum antibodies and RNA before transplantation. Although serum hepatitis C virus RNA was not detected after transplantation, serum enzyme immunosorbent assay and tissue core antigen were still detectable in both patients. In another child, serum hepatitis C virus RNA was positive and hepatitis C virus core antigen was found on a liver biopsy specimen but antihepatitis C virus antibodies were negative as well as liver hepatitis C virus RNA. No patient developed severe liver disease or cirrhosis during a follow up of up to 72 months. It is concluded that hepatitis C virus is a significant cause of morbidity after paediatric orthotopic liver transplantation. Diagnosis cannot rely on serological testing only. The patients remained stable on follow up, but longer prospective histological studies remain necessary to establish prognosis.
OBJECTIVE--To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN--Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING--Four major medical centres in the United States. PATIENTS--12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES--In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS--Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS--Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.
To determine the prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in entrants to Irish prisons and to examine risk factors for infection.
Cross sectional, anonymous survey, with self completed risk factor questionnaire and oral fluid specimen for antibody testing.
Five of seven committal prisons in the Republic of Ireland.
607 of the 718 consecutive prison entrants from 6 April to 1 May 1999.
Main outcome measures
Prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in prison entrants, and self reported risk factor status.
Prevalence of antibodies to hepatitis B core antigen was 37/596 (6%; 95% confidence interval 4% to 9%), to hepatitis C virus was 130/596 (22%; 19% to 25%), and to HIV was 12/596 (2%; 1% to 4%). A third of the respondents had never previously been in prison; these had the lowest prevalence of antibodies to hepatitis B core antigen (4/197, 2%), to hepatitis C (6/197, 3%), and to HIV (0/197). In total 29% of respondents (173/593) reported ever injecting drugs, but only 7% (14/197) of those entering prison for the first time reported doing so compared with 40% (157/394) of those previously in prison. Use of injected drugs was the most important predictor of antibodies to hepatitis B core antigen and hepatitis C virus.
Use of injected drugs and infection with hepatitis C virus are endemic in Irish prisons. A third of prison entrants were committed to prison for the first time. Only a small number of first time entrants were infected with one or more of the viruses. These findings confirm the need for increased infection control and harm reduction measures in Irish prisons.
What is already known on this topicHigh rates of using injected drugs, initiation of use of injected drugs, and sharing injecting equipment occur in Irish prisonsInjecting drug users have high rates of infection with hepatitis B and C viruses, and hepatitis C is endemic in injecting drug users and in Irish prisonersWhat this study addsThe prevalence of antibodies to hepatitis B core antigen, to hepatitis C, and to HIV in prison entrants who had previously been imprisoned was similar to that found in the recent national survey of Irish prisoners, but the prevalence of these antibodies was much lower in the third of prison entrants who had never previously been in prisonTattooing in prison is an independent risk factor for hepatitis C infection in prisoners who have never used injected drugs
Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7–14% and an incidence rate for liver cancer six times that of non-Latino whites.
Describe factors associated with hepatitis B testing among Vietnamese Americans.
A population-based telephone survey conducted in 2007–2008.
Vietnamese Americans age 18–64 and living in the Northern California and Washington, DC areas (N = 1,704).
Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing.
The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30–49 years, US residence for >10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt.
Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education.
hepatitis B; Vietnamese Americans; testing