anti-HBc IgG Research Articles

Direct role of antibody-secreting B cells in the severity of chronic hepatitis B.

Chronic hepatitis B involves different immune cells. The direct role of antibody-secreting B cells in the severity of chronic hepatitis B unclear. In this study, the number of plaque forming cells [PFC-(IgG, IgM, anti-HBc IgG, and anti-HBc IgM)], liver function tests (LFT) [alkaline phosphatase (ALP), alanine aminotransferase (ALT), and total serum bilirubin (TSB)], the levels of IL-10 in sera and in lymphocyte cultures, the number of CD4(+) and CD8(+) cells were measured in the peripheral blood of patients and in the controls. In addition, the hepatocytotoxic effect of anti-HBc and anti-HBe in vitro was studied. The largest number of PFCs was observed in the peripheral blood of patients with chronic hepatitis B. This was concomitant with a decrease in CD4(+) /CD8(+) ratio versus this ratio in asymptomatic HBV carriers and in healthy volunteers (P < 0.05). An increase in immunoglobulin (IgG and IgM) levels, anti-HBc IgG, and anti-HBc IgM levels and LFTs in peripheral blood of patients with chronic hepatitis B was seen. Anti-HBc induced hepatocytotoxicity in vitro. The expression of mRNA and protein for IL-10 production was observed at a significant level in culture of lymphocytes isolated from patients with chronic hepatitis B. In addition, a high level of IL-10 was found only in the sera of patients with chronic hepatitis B. It is concluded that the antibody-secreting B cells and the antibodies, which are produced, play an important role in the severity of chronic hepatitis B, which was related negatively with CD4(+) /CD8(+) ratio and positively with IL-10 expression.

The Prevalance of HBV, HCV and HIV Among Healthcare Workers in a Dental Hospital

OZET Objective: As healthcare professionals are exposed to infected blood samples, they are at increased risks of exposure to many infectious agents. The aim of the study was to investigate the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections among healthcare professionals and hospital staff at a dental hospital. Materials and Methods: A face to face questionnaire was carried out and HBsAg, anti-HBs, anti-HCV, and HIV antibody (anti-HIV) markers were analyzed from blood samples of 174 healthcare professionals at a dental hospital in Izmir via ELISA (Abbott, Wiesbaden, Germany) test. Results: None of the participants was positive for HBsAg, and 136 participants (78.1%) had positive anti-HBs. Of the anti-HBs-positive participants, 12 (8.8%) were positive for anti-HBc IgG. Anti-HCV positivity was detected in two participants, and the test results were confirmed with HCV RNA assay. HBV vaccination was recommended for participants unexposed to hepatitis B. Anti-HIV 1-2 was negative in all participants. Conclusion: In our study, immunity rates against HBV was high. This high rate was the result of high vaccination rates among the healthcare professionals. HCV prevalence among the healthcare professionals was similar to that in the general population. Hospital workers should be screened for HBV, HCV and HIV; individuals without HBV vaccination should be vaccinated, and all hospital personnel should receive training programs about the transmission of blood-borne infections. Training programs may prevent the possible infections. (Viral Hepatitis Journal 2014; 20(2): 75-77)

Detection of Hepatitis C virus RNA in peripheral blood mononuclear cells of patients with abnormal alanine transaminase in Ahvaz.

Hepatitis C virus (HCV) is an important agent for chronic and acute hepatitis. Occult hepatitis C remains a major health problem worldwide. Patients with chronic occult HCV may progress to cirrhosis and hepatocellular carcinoma. The aim of this study was to determine prevalence of occult hepatitis C by IS-PCR-ISH (in situ PCR in situ hybridisation) in the patients with abnormal ALT. The blood samples were taken from 53 patients including 17 females (32.1%) and 36 (67.9%) males who had abnormal alanine transaminase (ALT) for more than 1 year. The mean ALT and aspartate transaminase (AST) level were 41.02±9.3 and 24.17±7.3, respectively. The patients' age were between 4 and 70-years old with mean age 38±13. All the patients were negative for HCV antibody, HCV RNA and HBs Ag. The peripheral blood mononuclear cells (PBMC) were separated with ficoll gradient from each blood sample, then the cells were fixed on slides by cold acetone and followed by IS-PCR-ISH for HCV RNA detection. Seventeen (32%) patients including 6 (11.3%) females and 11 (20.7%) males showed positive results for HCV RNA by in situ-PCR in situ hybridisation. Ten (18.8%) positive cases were between 20 and 40-years old and 6 (11.3%) positive patients were between 40 and 60 years old. Ten (19.6%) patients who were positive for IS-PCR-ISH also had positive anti-HBc IgG and 7 (13.2%) patients were negative for HBc-IgG. In the present study high rate of 32% occult hepatitis C were found among the patients with elevated ALT.

High hepatitis B and low hepatitis C prevalence in Roma population in eastern Slovakia.

Viral hepatitis B and C prevalence in the Roma population of eastern Slovakia is largely unknown. This study aimed to explore the prevalence and associated risk factors of chronic viral hepatitis B and C among Roma living in segregated communities in eastern Slovakia. Data from the cross-sectional HepaMeta study conducted in Slovakia in 2011 among Roma living in rural communities were used. Participants were tested for the presence of HBsAg, anti-HBc IgG and anti-HCV. The risk factors were assessed mainly via a structured questionnaire/interview. Altogether 452 Roma were screened, and 11 were excluded due to missing data. A total of 441 patients were included (mean age 34.7 +/- 9.14 years; 35.2% men). 12.5% of participants were HBsAg positive, 40.4% anti-HBc IgG positive while negative for HBsAg and 47.2% of participants were negative for all serological markers of hepatitis B. Hepatitis C prevalence was very low (0.7%), while 2 out of 3 anti-HCV positive participants were coinfected with hepatitis B. Risk factors for hepatitis B infection were male sex, higher age, tattoo, and previous imprisonment. No difference was found in intravenous drug use, blood transfusions and sexual behaviour. More than half of the Roma residing in eastern Slovakia have been infected at one point in life with the hepatitis B virus, and 12.5% are HBsAg positive. Hepatitis C prevalence is very low, which is probably due to very low intravenous drug use.

Association between metabolic syndrome and hepatitis B virus infection in the Roma population in eastern Slovakia: a population-based study.

The simultaneous presence of chronic hepatitis B (CHB) and metabolic syndrome (MS) in the high-risk Roma community constitutes a high risk for liver cirrhosis and potentially hepatocellular carcinoma. This study aims to explore the relationship between MS and CHB. Data from the cross-sectional HepaMeta Study conducted in Slovakia in 2011 among Roma living in rural communities were used. Participants were tested for the presence of MS, and lipid levels--total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (TG), apolipoprotein B100, and CHB HBsAg and anti-HBc IgG were also monitored. Viral load was measured in HBsAg-positive patients. A total of 452 patients were screened; MS was diagnosed in 29.6% of patients, and 12.5% had CHB. Anti-HBc IgG antibodies were present in 52.8% of patients. CHB patients had lower levels of total cholesterol (5.45 +/-1.21 vs. 4.71 +/- 1.23 mmol/l; p = 0.035), LDL cholesterol (median 2.2 mmol/l, interquartile range 0.88 mmol/l vs. 2.5 mmol/l, interquartile range 0.9 mmol/l; p = 0.01) and apolipoprotein B100 (median 0.66 mmol/l, interquartile range 0.26 mmol/l vs. 0.74 mmol/l, interquartile range 0.29 mmol/l; p = 0.025). Patients diagnosed with MS had a higher HBV DNA load than patients without MS (1,728.2 +/- 14.33 IU/ml vs. 12,779.1 +/- 20.9 IU/ml; p = 0.037). CHB patients with TC and apolipoprotein B100 within the reference range had a lower hepatitis B DNA (HBV DNA) load than patients with high or low values of TC or apolipoprotein B100. The prevalence of chronic hepatitis B and simultaneous presence of MS was high among Roma. HBsAg-positive patients had lower levels of total and LDL cholesterol along with decreased apolipoprotein B100. The viral load of chronic hepatitis B patients with MS was higher than in patients without MS.

Prevalence of genotype D in chronic liver disease patients with occult HBV infection in northern region of India.

Etiology of nearly 30% cases of chronic viral hepatitis remains undetected. Occult HBV infection (OBI) has emerged as an important clinical entity in this scenario. Apart from prevalence and clinical outcome of OBI patients genotype was determined in northern region of India. A total of 847 patients with chronic liver disease (CLD) were screened for common viral etiologies and others serological markers of HBV. Amplification of surface, precore and polymerase genes of HBV was performed in patients negative for other etiologies. Genotyping and sequencing of the precore region was performed for OBI cases. Twenty-nine (7.61%) cases of OBI were identifiedof which 9 had chronic liver disease (CHD), 11 liver cirrhosis (LC) and 9 hepatocellular carcinoma (HCC). Majority of OBI cases were detected by amplification of surface gene 26 (89.6%), followed by pre-core gene 12 (41.3%). Their liver functions tests were significantly deranged in comparison to overt HBV cases. IgG anti HBc was present in 8 (27.6%) OBI cases. Mutation was observed in 8 (32%) in pre-core region at nt. 1896 of overt HBV cases. Genotype D was the predominant genotype. OBI in our study was characterized by predominance of genotype D and more severe clinical and biochemical profile in comparison to overt HBV. IgG anti HBc positivity could be utilized as a marker of OBI. We recommend use of sensitive nested PCR for diagnosis of OBI, amplifying at least surface and precore gene.

Elazığ Harput Devlet Hastanesi Çalışanlarında Hepatit B ve C Seroprevalansı

Aim: To evaluate the seroprevalence of hepatitis B and C infections among health-care workers in Elazig Harput State Hospital. Methods: Hepatitis B and C virus markers (HBsAg, Anti-HBs, AntiHBc IgM, Anti-HBc IgG, Anti-HCV) of 498 health-care persons were retrospectively investigated in this study between July-August 2007 in Elazig Harput State Hospital. Results: A total 20 (4%) health-care workers were positive for HBsAg, 174 (34.9%) for anti-HBs, 4 (0.8%) for anti-HBs as well as anti-HBc IgG, and 2 (0.4%) for anti-HCV. There were no statistical significant differences in point of HBsAg positivity among health-care workers (p>0.05). Anti-HBs positivity was statistically significant high among nurses compared to the others health-care workers (p=0.001). A total 308 (61.8%) health-care workers were seronegative against hepatitis B. Conclusion: The high seronegativity rate against hepatitis B among health-care workers has shown to need to vaccination and education for hepatitis B infection

Hepatitis B Related Serological Events In Hematopoietic Stem Cell Transplant Patients and Efficacy Of Lamivudine Prophylaxis Against Reactivation

IntroductionRemote Hepatitis B Infection (RHBI) is an immunological stage in the life cycle of Hepatitis B virus (HBV). It is characterized by the persistence of HBV DNA at low level within the liver or blood of people infected in past. As a result HBsAg, HBeAg and HBV DNA in serum are negative while Anti-HBs and/or Anti-HBc IgG are positive with normal liver enzymes. In Hematopoietic stem cell transplant (HSCT) patients, reactivation of RHBI leads to increased HBV replication and increased HBV DNA titres in blood and/or HBsAg or HBeAg positivity. There may be loss or gain of Anti-HBs and/or Anti-HBc IgG. The importance of recognizing this stage with a potential for reactivation is highlighted by the fact that: 1) HBV reactivation can lead to fulminant hepatitis & 2) Anti-HBV therapy such as lamivudine can prevent HBV reactivation. In this study we have aimed to determine the incidence of RHBI and HBV reactivation in our patients, the role of lamivudine in preventing HBV reactivation and the pattern of change in serological markers after reactivation. MethodsAll patients undergoing HSCT from March 2010 to May 2013 were included. Pre transplant, all patients were tested by ELISA for HBsAg, Anti-HBs, Anti-HBc IgM and Anti-HBc IgG. Post transplant, at the time of deranged liver function, all patients were tested for HBsAg, Anti-HBs, Anti-HBc IgM, Anti-HBc IgG, Anti-HCV, Anti-HEV and Anti-HAV. HBV DNA and HCV RNA were tested by polymerase chain reaction. RHBI was defined as positive Anti-HBc IgG and/or Anti-HBs (without history of HBV vaccination) with negative HBsAg and Anti-HBc IgM and normal liver function. HBV reactivation was defined as increase in transaminases to more than 3 times the upper limit of normal with HBV DNA and/or Anti-HBs and/or Anti-HBc IgG positivity (HBsAg and Anti-Hbc IgM being negative) at the time of deranged liver function. Lamivudine at a dose of 100 mg/d or 3 mg/kg/d (children <12 years) was given to all but one patient with Anti-HBc IgG positivity pre transplant irrespective of Anti-HBs positivity (Prophylaxis Group). Patients who had only Anti-HBs positivity did not receive prophylaxis (No Prophylaxis Group). Data was analyzed to explore the role of prophylactic lamivudine in preventing HBV reactivation and to determine the pattern of change of HBV serological markers at the time of reactivation. The time to respond to lamivudine was calculated as the interval from start of prophylaxis to normalization of liver enzymes. ResultsTwo hundred five patients underwent HSCT (autologous - 103 and allogeneic - 102) from March 2010 to May 2013. Twenty-eight (14%) patients were diagnosed to have RHBI (autologous-9, allogeneic-19). Thirteen patients did not receive prophylactic lamivudine (No-Prophylaxis Group) while 15 patients received prophylactic lamivudine (Prophylaxis Group). Twelve (92%) patients in No-Prophylaxis Group developed HBV reactivation while none (0%) in the Prophylaxis Group (P<0.001). The incidence of HBV reactivation was 10% (21 of 205 patients) which included 11 (52%) with only Anti-HBs positive, 1 with only Anti-HBc IgG positive and nine (43%) with all HBV serological markers negative (i.e. no evidence of RHBI) pre transplant. Six of these 9 patients sero-converted (5 - Anti-HBc IgG and 1 - Anti-HBs positive) at the time of reactivation. Seven (33%) developed HBV viremia at the time of HBV reactivation, of which 6 were Anti-HBs negative pre transplant. In contrast, of the patients with undetectable HBV DNA at the time of reactivation (14 patients), only 4(29%) were Anti-HBs negative pre transplant (P=0.0237). Seven (33%) patients were on steroids and 9(43%) were on cyclosporine at the time of reactivation. All patients responded to lamivudine within a median time of 17 days. ConclusionsIncidence of RHBI in patients undergoing HSCT is high in our setting.Lamivudine prophylaxis protects against HBV reactivation post transplant. We would recommend lamivudine prophylaxis in patients with RHBI with isolated Anti-HBs positivity in addition to those with Anti-HBc IgG positivity given the high rate of HBV reactivation in these patients.All serological markers for Hepatitis B being negative pre transplant does not preclude HBV reactivation post transplant. Therefore, all serological markers for HBV should be repeated at the time of deranged liver functions post transplant.Anti-HBs positivity pre transplant decreases the risk of HBV viremia at the time of reactivation. Disclosures:No relevant conflicts of interest to declare.

Seroprevalence of hepatitis B in two period birth cohorts of Bolivian children: effect of universal vaccination

Since 2000 universal routine immunization against the hepatitis B virus (HBV) was implemented in Bolivia. This study aimed to assess the seroprevalence of markers against HBV in two different birth cohorts (pre-universal vaccine cohort and post-universal vaccine cohort) from Cochabamba, Bolivia. We performed a school-based seroepidemiological survey (n = 424) of HBV in 2010 in the Cochabamba region. An ELISA test was used to measure antibodies to the hepatitis B surface antigen (anti-HBs IgG) and to the hepatitis B core antigen (anti-HBc IgG). The prevalence of anti-HBs IgG in the pre-universal vaccine cohort was 5.8% (95% CI: 3.3-8.3%); it was higher in boys (9.1%), and those living in suburbs (9.7%). The anti-HBs IgG prevalence among post-universal vaccine cohort was 37.9% (95% CI: 28.5-48.1%), and was higher in children who spoke Quechua at home (51.0%), those living in suburbs (53.9%), and those born in 2005 (72.7%). Neither cohort showed differences relating to parental education. The prevalence of anti-HBc IgG was 1.1% among post-universal vaccine cohort and 1.2% among pre-universal vaccine cohort (p > 0.05). This study identified a persistent low seroprevalence of hepatitis B infection in spite of a decade of universal immunization, and low long-term humoral immunity against HBV infection in vaccinated children in Cochabamba.

FRI0190 Safety of certolizumab pegol in rheumatoid arthritis patients with previous hepatitis b virus exposure.

ObjectivesTNFα is a key cytokine in the integrated host defence system against infectious diseases, acting on both the innate and the adaptive immune system. Anti-TNF agents may elicit Hepatitis B...

AB0740 The frequency of occult hepatitis b infection in rheumatic diseases and the role of anti-hbc test in routine practice

BackgroundMost of the drugs used in rheumatic diseases suppress the immune system, especially corticosteroids and anti-TNF agents, therefore may cause reactivation in patients with hepatitis B virus (HBV). Studies have...

Prevalence of Pretransplant Infections among South East Asian Kidney Transplant Recipients

Introduction: Although a number of solid organ transplantation has been rising in South East Asia, data on the prevalence and type of pretransplant infections is small. Methods: Between January 2006 and December 2011, we prospectively screened adult (age ≥18 years old) kidney transplant (KT) candidates from South East Asian Countries who underwent kidney transplantation at our center for pretransplant latent infections. We performed serological testing for viruses (HIV, HBV, HCV, CMV, VZV, HSV, EBV), strongyloides and syphillis, CBC with differential, and chest radiography. In addition, endemic parasites were tested by serology and stool examination among the candidates with peripheral eosinophila. During the same study period, pretransplant screening of the donors (anti-HIV, HBsAg, anti-HCV, anti-HBs antibody, VDRL) was done according to the standard protocol of the Thai red cross. Since 2009, thick smear and/rapid test for malaria were done among non-Thai living donors and candidates from endemic area following our first case of malaria infection early post transplantation. Results: Of the 181 KT recipients, 61.9% were Thais, 32.6% were Myanmars and 5.5% were Cambodians. The recipients, median age was 53 (15-75) years old. Majority (63%) were male. None were anti-HIV positive. Among the recipients, high rate of latent infections included varicella zoster virus (99.4%), herpes simplex virus (98.8%), cytomegalovirus (97.2%), and epstein-barr virus (95.3%). Majority (74%) of the recipients and 47.2 % of the donors had protective immunity to hepatitis B, respectively. Positive antiHBc IgG, HBsAg, and anti-HCV was noted in 57.1%, 5% and none of the donors, and 57.7%, 10.5%, and 2.2% of the recipients, respectively. Abnormal chest radiography suspicious for remote pulmonary infection was noted in 7.2%. None of the patients had an evidence of malaria infection. Only one (0.6%) patient was tested positive for strongyloides latent infection without clinical symptoms and negative stool examination. One (0.6%) patient had peripheral eosinophilia and were tested positive for gnathosomiasis by serology without clinical symptoms/signs. Both of the patients subsequently received anti-helminthic agent as treatment pretransplantation, as well as the repeated course of treatment post transplantation. No relapse of the infections was noted after 6 months follow up. Conclusions: The prevalence of latent herpes viral infections among South East Asian transplant candidates was high but the overall prevalence of parasitic infections was low. Nevertheless, pre-transplant infectious disease screening remains a critical step in preventing post transplant related-complication from donor-derived and reactivation of latent infection.

Hepatitis B and C Virus Infection and Cholangiocarcinoma: A Case-Control Study in Turkey

Hepatitis B and C virus (HBV and HCV) infection have been proposed as risk factors for cholangiocarcinoma, but the results are in- consistent through different reports. This study is to carry out a hospital-based case-control study to investigate the association bet- ween HBV and HCV infection and cholangiocarcinoma in Turkey. A total of 127 cases and 48 matched controls were included in the study. There were 89 cases with extrahepatic cholangiocarcinoma, 10 cases with intrahepatic cholangiocarcinoma and 28 ca- ses with gallbladder cancer. The patients and controls were questioned on smoking, alcohol drinking, history of cholecystolithiasis, choledocholithiasis and hepatolithiasis. Blood from all participants were tested for HBsAg, Anti-HBs, Anti-HBc IgG and Anti-HCV. The prevalence of smoking, alcohol drinking, cholecystolithiasis, choledocolithiasis, hepatolithiasis, anti-HCV, HBsAg and anti- HBs/anti-HbcIgG did not differ significantly between the patients and controls (p>0.05). In the subgroup analysis there was no sig- nificantly more prevalent risk factor except smoking in intrahepatic cholangiocarcinoma (p= 0.019). In conclusion, HBV or HCV in- fection were not found to be risk factors for development of CC in this study.

Prevalence and clinical significance of occult hepatitis B virus infection among renal transplant recipients in Korea

Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in serum or hepatic tissue without detectable hepatitis B surface antigen (HBsAg) in serum. Kidney disease patients in the post-renal transplantation period are in a specific situation as a result of the high pre-transplantational risk of HBV infection and post-transplantational immunosuppression. We studied the pre-transplantational prevalence and post-transplantational influence of OBI on kidney transplantation patients. We investigated pre-transplantational serum samples of 217 HBsAg-negative patients of post-renal transplant status for the presence of HBV DNA by real-time quantitative polymerase chain reaction. Serologic markers for HBV and hepatitis C virus (HCV) infection as well as liver enzymes were analyzed. We detected HBV DNA in 2.3% (5/217) of HBsAg-negative patients, and the median HBV DNA titer was 33.15 copies/ml (range 30.6-144.6 copies/ml). Among the 5 OBI patients, 2 had hepatitis B surface antibodies (anti-HBs) and 1 had hepatitis B core antibodies (anti-HBc IgG). None of the patients with OBI were co-infected with HCV. There was no evidence of reactivation of OBI during the 36-month (range 27-63 months) follow-up monitoring period after transplantation, in spite of immune suppression to prevent rejection. The prevalence of occult HBV in the setting of renal transplantation was higher than that in the general population of Korea, and no reactivation of hepatitis B was observed in patients with OBI in the post-renal transplantation period.

Drohendes Leberversagen nach Chemoimmuntherapie-induzierter Reaktivierung einer Hepatitis B - erfolgreiche Therapie mit Entecavir

An 83-year old woman had been treated with bendamustin and rituximab for prolymphocytic leukemia. Two weeks after cycle 6 of chemotherapy, signs and symptoms of a severe hepatitis occurred. Highly elevated values for AST (1353 U/l) and bilirubin (27.8 mg/dl), impaired coagulation parameters (INR 1,68) and the detection of ascites led to the diagnosis of an impending liver failure induced by reactivation of a hitherto unknown hepatitis B (HBs antigen pos., HBe antigen pos., anti HBc IgG pos., HBV DNA 1,65 Mio copies/ml). After an immediately started treatment with entecavir (0.5 mg/d po), symptoms and laboratory parameters rapidly improved. 4 months later liver chemistry was completely normal and HBV DNA was negative. After 8 months, a seroconversion to anti HBs was noted. In single cases, life threatening complications of chemotherapy induced reactivation of hepatitis B may be successfully treated by potent and stabile nucleosidanalogs.

21 PREVALENCE OF OCCULT HEPATITIS B INFECTION IN PATIENTS WITH DECOMPENSATED CIRRHOSIS IN A TERTIARY CARE TEACHING HOSPITAL IN SOUTH INDIA

Background: Occult hepatitis B infection (OBI) is detection of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in persons who are hepatitis B surface antigen (HBsAg) negative. It is classified into seropositive and seronegative infection depending on the positivity for anti-HBc and anti-HBs titer. In majority cases of decompensated cirrhosis, particularly those patients who are referred to tertiary care hospital as cryptogenic cirrhosis, OBI infection forms an important treatable etiology, so also in patients anticipating organ transplantation, blood transfusion, surgery, hemodialysis and immunosuppressive drugs. Testing the patient for OBI may minimize many sophisticated investigations. Aim: To study the prevalence of OBI in adult patients presenting with decompensated cirrhosis. Method: Hospital based descriptive study. Adult patients admitted with decompensated cirrhosis as a part of evaluation IgG anti-HBc (hepatitis B core), HBV-DNA, antiHBs titer and other relevant parameters were analyzed. Study Period: July to December 2011. Result: Total number of patients (n) were 45, with males 34 (75.6%) and females 11 (24.4%). Among these, 39 (86.7%) were positive and 6 (13.3%) were negative for IgG anti-HBc. Three among the positive group (6.66%) and two among the negative group (4.44%) were positive for HBV-DNA with total five patients (11.1%). Patients among negative group (seronegative OBI) were presented with very high DNA level. Anti-HBs titers were not correlated with HBVDNA or IgG anti-HBc. Conclusion: The prevalence of OBI is 11.1%. Seronegative OBI was presented with very high DNA levels. No correlation of anti-HBs titer with OBI was observed. control group. The prevalence of gallstone was higher in the CC group (57.4% vs 10.8%; P < 0.05) of which four (8.69%) were symptomatic. Conclusion: Our study showed that there is an undue preponderance of components of metabolic syndrome in patients with CC when compared with cirrhosis of other etiology. Metabolic syndrome and its components may be considered an important cause or risk factors for CC.

Spectrum of hepatitis B infection in Southern India: A cross-sectional analysis

Background and Aim: Hepatitis B virus (HBV)-related liver disease is not an uncommon problem in India. There are very few reports on pattern of chronic HBV infection from South India. The aim of the present study was to determine the spectrum of chronic HBV infection among patients attending the liver clinic in a tertiary referral center. Materials and Methods: Hepatitis B surface antigen (HBsAg) positive patients registered in the liver clinic between July 2010 and March 2011 were included in the study. All patients had baseline liver function tests, serological markers for HBV infection (hepatitis B e antigen [HBeAg], anti-HBe, anti-HBc total, and anti-HBc IgG, and HBV DNA quantification), serum alpha-fetoprotein, and ultrasound. Based on the viral profile and transaminase levels and ultrasound findings, patients were categorized as immunotolerant, inactive carriers, immune clearance and reactivation phase, and chronic liver disease with or without hepatocellular carcinoma. Results: Majority of the patients were asymptomatic and incidentally detected during blood donation camps, master health checkup (MHC), or during initial screening. Almost 40% of patients were either in immune inactive phase or had features of chronic liver disease. In the immunotolerant phase (24 patients), women were a decade younger than their male counterparts. Alanine aminotransferase (ALT) levels were similar in both HBeAg-positive and negative patients. The mean HBV DNA values were significantly high in HBeAg-positive men and women. In the immune inactive phase (58 patients), there were only three patients who were HBeAg positive. The ALT levels were in the normal range. HBV DNA values were low or not detectable. Among patients with elevated ALT and HBV DNA levels (immune clearance/immune reactive) (fifty patients), the mean ALT levels were higher in HBeAg-negative patients. HBV DNA quantity was significantly high in patients who were HBeAg positive. Conclusion: A significant proportion of HBsAg-positive patients is in inactive or in immunotolerant phase and do not require treatment. Patients with elevated ALT and HBV DNA levels need further evaluation to categorize them into immune clearance or immune reactive phase.

Methylprednisolone and Hepatotoxicity in Graves' Ophthalmopathy

Immunosuppressive therapy with glucocorticoids alone or in combination with radiotherapy is first-choice treatment for the active phase of Graves' ophthalmopathy (GO). Intravenous methylprednisolone (mPRED) pulse therapy is much more effective, safer, and better tolerated than steroids orally administered. There have been some reports, however, of unfavorable reactions to mPRED pulse therapy on liver function. Here, we report laboratory test results in patients with GO before and after intravenous mPRED therapy. Thirty patients (24 women and 6 men) whose mean age was ± standard error of the mean 53±1.3 participated in the study. All patients were treated with mPRED for their history of GO. None had received radiotherapy before mPRED. There was no history of liver disease including viral hepatitis in any of the patients. A battery of tests including general serum chemistries and liver function tests as well as those relating to clotting parameters and viral forms of hepatitis were performed a week before and 2 days after mPRED therapy. mPRED pulse therapy caused a significant, below reference range, decrease in alkaline phosphatase activity from 119.43±14.98 to 105.53±13.98 IU/L and an increase in gamma-glutamyltranspeptidase activity (above reference range, but not statistically significant) from 23.76±2.93 to 25.3±1.52 IU/L. No significant changes were noted in other liver enzymes activities. We also observed a significant, below reference range, decrease in serum total protein as well as a significant, above reference range, increase of alpha-1 globulins, and low-density lipoproteins cholesterol levels. Pulse therapy also resulted in a significant, but still within reference range, decreases in activated partial thromboplastin time (APTT) from 29.03±0.86 to 26.13±1.16 s, fibrinogen from 3.85±0.2 to 3.05±0.13 g/L, and increase of International Normalized Ratio (INR) from 1.06±1.06 to 1.11±0.06. Despite a lack of a history of viral hepatitis, six patients had positive tests for anti-Hepatitis B e (HBe) antibodies before mPRED administration. In two of these patients, anti-HBe antibody tests became negative after mPRED treatment. In two of the six patients who had positive anti-HBe antibodies, anti-HBc antibodies in the IgG class were also present before and after mPRED treatment. Another patient was found to have anti-HBc IgG both before and after mPRED treatment. Other markers of A and C viral hepatitis were negative in all patients. Patients who are on anticoagulents need careful monitoring of their INR, APTT, and fibrinogen while on mPRED therapy. We recommend at least once a week. In patients without evidence for active viral replicating disease, but with past hepatitis B, as judged by the presence of pertinent markers, mPRED pulse therapy for GO does not appear to reactivate hepatitis B.

Prevalence of immunity to hepatitis viruses A and B in a large cohort of HIV/HCV-coinfected patients, and factors associated with HAV and HBV vaccination

Hepatitis A (HAV) and B (HBV) vaccination is strongly recommended for HIV-infected patients, especially those with hepatitis C coinfection. The aim of this study was to determine the prevalence of antibodies directed against HAV and HBV in a large cohort of HIV/HCV-coinfected patients, and to identify factors associated with HAV and HBV vaccination. We studied 1175 HIV/HCV-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort, whose HAV and HBV serostatus was known. 1056 patients (89.9%) have been tested for anti-HBc IgG, anti-HBs, and HbsAg. Only 10.9% of patients had received HBV vaccination and 70% of the patients with no HBV immunity (231/265) had never received HBV vaccination. In multivariate analysis, male sex (OR 2.0. 95% CI 1.1-3.8; p=0.02), a higher level of school education (OR 2.5, 95% CI 1.3-4.5; p=0.003), a higher CD4 cell nadir (OR 1.05, 95% CI 1.009-1.103; p=0.018) and no cirrhosis (OR 2.7, 95% CI 1.2-6.4; p=0.02) were associated with HBV vaccination. Only 368 patients (31.3%) were tested for immunity to HAV. Despite a frequent lack of HAV immunity (48.3%), a low rate of HAV vaccination (6%) was observed. In multivariate analysis, a higher level of school education (OR 3.6, 95% CI 1.03-12.4; p=0.045) was the only factor associated with HAV vaccination. HAV screening rates and HAV and HBV vaccination rates were low in this population of HIV/HCV-coinfected patients. The benefits of routine HAV and HBV screening, vaccination and post-vaccination testing should be emphasized.

Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice

: Background: Nearly 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory protein, ubiquitous in eukaryotes, that usually serves as a signal for the target protein that is recognised and degraded in proteasomes . The Ub-mediated processing of antigens is rapid and efficient and stimulates cell-mediated immune responses. Accordingly, Ub-mediated processing of antigens has been widely used in chronic-infection and cancer studies to improve immune response.Objectives: Many clinical trials have shown that DNA vaccine potency needs to be greatly enhanced. Here, we report a new strategy for designing an HBV DNA vaccine using the ubiquitin (Ub) sequence. The aim of this study was to investigate a novel DNA vaccination, based on the expression of HBV core antigen (HBcAg), fused to Ub to enhance DNA vaccine potency.Materials and Methods: Mouse ubiquitin fused to the HBcAg gene and cloned into the eukaryotic vector pcDNA3.1 (-). BALB/c mice were immunized with recombinant pUb-HBcAg or pHBcAg DNA vaccine. Lymphocyte proliferation assay, intracellular IFN-γ assay, CTL cytotoxicity assay, and antibody assay were performed to analyze the cellular and humoral immune responses to our DNA constructs.Results: HBcAg was expressed effectively in the COS-7 cells that were transiently transfected with pUb-HBcAg. Strong anti-HBc IgG responses were elicited in mice that were immunized with pUb-HBcAg. The endpoint titers of anti-HBc peaked at 1:656100 on the 42nd day after the third immunization. pUb-HBcAg stimulated greater lymphocyte proliferation and induced higher levels of IL-2 and IFN-γ and a greater percentage of HBcAg-specific CD8+ T cells in mice than pHBcAg. In the CTL assay, the specific lysis rate reached 56.5% at an effector:target ratio of 50:1 in mice that were immunized with pUb-HBcAg.Conclusions: pUb-HBcAg elicits specific anti-HBc responses and induces HBc-specific CTL responses in immunized BALB/c mice. Our results imply that Ub can be used as a molecular adjuvant that enhances the potency of DNA vaccines.Keywords: DNA vaccine; Ubiquitin; Hepatitis B core antigen Implication for health policy/practice/research/medical education:This strategy may have therapeutic value that can be applied to the treatment of infectious diseases. Please cite this paper as:Chen JH, Yu YS, Liu HH, Chen XH, Xi M, Zang GQ, et al. Ubiquitin Conjugation of Hepatitis B Virus Core Antigen DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response in BALB/c Mice. Hepat Mon. 2011;11(8):620-8. [DOI: 10.5812/kowsar.1735143X.689] ©2011 Kowsar M.P.Co. All rights reserved.