HBeAg Positivity Research Articles

Factors associated with access to antiviral treatment in a multicentre cross‐sectional study of patients with chronic hepatitis B in Italy

A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1-1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1-2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2-6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02-2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4-10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5-0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5-0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5-0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3-0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.

Relationship of HLA-DRB1 Alleles With Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients

We intended to analyze the relationship between specific human leukocyte antigen (HLA)-DRB1 alleles and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. A database of 468 consecutive CHB patients who received lamivudine for more than 12 months between July 1996 and February 2011 was retrospectively analyzed. Sera and buffy coats samples were obtained between April 2008 and April 2010. Six-digit HLA-DRB1 genotyping was performed with sequence-based typing. Serum α fetoprotein levels and ultrasonography or computed tomography image studies were assessed every 3 to 6 months for surveillance of HCC. At baseline, median age was 43 years (range, 16 to 71) [male: 359 (76.7%); HBeAg positivity: 385 (82.3%)]. Among the 27 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent (>10%). HCC was diagnosed in 36 (7.7%) patients during the median follow-up of 69 months. The frequency of the HLA-DRB1*140101 allele was 9.0% and significantly higher in patients of the HCC group than those of the non-HCC group (19.4 vs. 8.1%, P=0.014). The 2-year, 4-year, and 6-year cumulative rates of HCC development were markedly higher in patients with HLA-DRB1*140101 than those without HLA-DRB1*140101 (2.4, 8.2, and 25.1% vs. 1.9, 4.7, and 7.4%, respectively, P=0.011). No other HLA-DRB1 alleles were associated with HCC development. Baseline clinical characteristics did not differ between patients with and without HLA-DRB1*140101. The HLA-DRB1*140101 allele may be potentially associated with increased risk of HCC development in CHB patients, irrespective of the replicative activity of hepatitis B virus and antiviral responsiveness.

Entecavir as specific antiviral therapy in selected cases of severe acute hepatitis B

The role of specific antiviral treatment in severe acute hepatitis B has been subject to debate during the past few years. We present clinical findings in a series of three cases of severe acute hepatitis B and one case of acute hepatitis B treated with entecavir during 2007-2009, with interesting evolution. Entecavir appeared to improve the clinical evolution in the reported cases. Two of the patients displayed HBsAg to HBsAb seroconversion while another patient went into an inactive HBsAg carrier state. In the case of mild acute hepatitis B, the liver enzymes had returned to normal, symptomatology had receded but HBsAg had remained positive. Without data on viral load, we were unable to determine whether the patient had entered an inactive HBsAg carrier state or had continued into the services of another medical unit, for treatment of chronic HBV infection. We also discuss into detail a case which displayed transient initial HBe seroconversion at 1 week, followed by seroreversion to positive HBeAg and negative HBeAb at week 3, and a new seroconversion at week 7. We assess the possible roles of precore mutations, antibody-dependent cellular cytotoxicity, coinfection with Epstein Barr virus and the function of Kupffer cells.

Changes in the serum level of hepatitis B virus (HBV) surface antigen over the natural course of HBV infection

Despite its status as a potential biomarker of hepatitis B virus (HBV) response to interferon treatment, the changes in hepatitis B surface antigen (HBsAg) levels over the natural course of HBV carriers have not been analyzed sufficiently. A total of 101 HBV carriers were followed prospectively from 1999 to 2009. HBsAg level was measured yearly during the followed period. HBsAg levels at baseline ranged from -1.4 to 5.32 log IU/ml, with a median value of 3.2 log IU/ml. Lower HBsAg levels were significantly associated with higher age and lower HBV replication status. The rate of change of HBsAg levels showed two peaks, with a cut-off value of -0.4 log IU/year. Based on this, patients were tentatively classified into rapid decrease (rate of change <-0.4 log IU/year) and non-rapid decrease groups. All baseline levels of HBsAg, HB core-related Ag, and HBV DNA were lower in the rapid decrease group than in the non-rapid decrease group. Patients with persistently positive HBeAg were all classified into the non-rapid decrease group. In patients with persistently negative HBeAg, HBV DNA levels were significantly (P = 0.028) lower in the rapid decrease group than in the non-rapid decrease group. Lower baseline HBsAg levels were significantly associated with older age and lower viral activity. Both a loss of HBeAg detection as well as inactive replication of HBV are suggested to be fundamental factors contributing to a rapid decrease in HBsAg over the natural course of HBV infection.

Detection of HBV-DNA and Its Correlation with the HBeAg/Anti-HBe Serological Status in HBsAg-positive Patients

Background : In the past years, HBeAg and anti-HBe status in individuals with positive HBsAg were often correlated to viral replication. This study was aimed to find correlation between the HBV viremia and HBeAg/anti-HBe serological status in HBsAg-positive individuals. Method : An observational-analytic design was performed in this study. The sera of all positive HBsAg patients at Biomedika Hospital Laboratory were collected and examined for HBeAg and anti-HBe using immunochromatography technique between January and April 2012. The sampling method was purposive sampling. Afterwards, the sera were examined for HBV-DNA by polymerase chain reaction (PCR). Results: Sufficient amount of sera were collected from 44 patients consisting of 33 males and 11 females. The mean age was 15-68 years. Positive HBeAg and negative anti-HBe status was found in 11 (42%) patients. Negative HBeAg and positive anti-HBe was found in 26 (59.1%) patients. Both HBeAg and anti-HBe were negative in 7 (16.3%) patients. HBV-DNA was detected in all 11 (100%) patients with positive HBeAg and negative anti-HBe. HBV-DNA was also detected in 11 (42%) patients with negative HBeAg and positive anti-HBe. However, there was only one patient (14.3%) with both negative HBeAg and anti-HBe status, who had detectable HBV-DNA. Conclusion: Positive HBeAg can be used as an indicator of viremia, but negative HBeAg cannot be used as an indicator of the absence of viremia without further HBV-DNA testing. Patients with negative HBeAg and positive HBV-DNA were suspected for having pre-core mutant. Keywords : HBV-DNA, positive HBsAg, HBeAg, anti-HBe, pre-core mutant

Diagnostic incidence of the presence of positive HBsAg: epidemiologic, clinical, and virological characteristics

To analyze the epidemiological, clinical, and virological characteristics of patients newly diagnosed with active hepatitis B virus (HBV) infection based on the presence of positive hepatitis B surface antigen (HBsAg) in the digestive diseases department of a district hospital. We performed a 3-year prospective study in patients newly diagnosed with HBV infection. We analyzed epidemiological, clinical, and virological characteristics, complete HBV markers, quantification of HBV DNA, and infection by hepatitis delta virus. We performed genotyping and resistance testing in patients with a high viral load. Results were obtained for patientswho required liver biopsy. We diagnosed 213 patients (18.8/10,000 inhabitants/year). Men accounted for 61%, and 59% were aged 20 to 40 years. Immigrants accounted for 53% of the population: 46% were from Rumania and 37% from Sub-Saharan African countries. At diagnosis, 2.3% had acute hepatitis (all with jaundice) and 3.3% had cirrhosis with portal hypertension. With the exception of cases of acute hepatitis, positive HBeAg was observed in 9%. Serum transaminase levels were normal in 62.2% of patients, HBV DNA was > 2,000 IU/mL in 33.8%, and delta virus was present in 3.3%. Genotyping and resistance testing were performed in 70 patients: the most common genotype was D, followed by A. Resistance was detected at baseline in only 2 cases: to adefovir in one case and to entecavir in another. Among the 36 biopsies performed, 32.4% showed inflammatory activity > or = 2, and 23.5% had fibrosis > or = 2 according to the METAVIR scoring system. According to clinical practice, specific treatment for HBV infection was necessary (any reason) in 17.4% of those diagnosed (3 patients per 100,000 inhabitants/year). Despite prevention and vaccination, HBV infection is a health problem that most commonly affects the immigrant population and men. Serum transaminase levels are normal in 62.2% of patients. The most frequent genotype is D, followed by A, and baseline resistance is scarce.

Detection of core antigen of hepatitis virus C in patients infected with hepatitis virus C and B

To observe the effect of hepatitis virus B on the detection rate of core antigen of hepatitis virus C in sera of chronic hepatitis C patients. HCVcAg and HCV RNA in sera were detected in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV. At the same time, HBV DNA and HBeAg in sera were detected in 62 patients infected with HCV and HBV. Then we analyzed the correlation between HCVcAg and HBeAg/HBV DNA. The detection rates of HCVcAg in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV were 72.7% (64/88) and 38.7% (24/62), respectively (x2 = 17.358, P less than 0.01). The detection rates of HCV RNA in 88 patients with chronic hepatitis C and 62 patients co-infected with HCV and HBV was 81.8% (72/88) and 53.2% (33/62)respectively (x2=20.110, P less than 0.01). In 62 patients infected with HCV and HBV, the detection rate of HCVcAg in HBeAg positive patients and HBeAg negative patients were 28.6% (12/42) and 60% (12/20), respectively (x2 = 7.547, P = 0.011). Moreover, the positive rates of HBV DNA in HBeAg positive patients and HBeAg negative patients were 42.9% (18/42) and 80% (16/20), respectively (P more than 0.05). The detection rates of HCVcAg in HBV DNA positive patients and HBV DNA negative patients were 39.1% (18/46) and 37.5% (6/16), respectively (x2 = 0.013, P = 0.908). Compared with the detection rates of HCVcAg in patients only infected with HCV, the detection rate of HCVcAg in HBeAg or HBV DNA negative patients infected with HCV and HBV were 60% (12/20) (x2 = 1.266, P = 0.261) and 37.5% (6/16) (x2 =7.635, P less than 0.01), respectively. The detection rate of HCVcAg in patients infected with HCV and HBV is relatively low. The reason is possibly that HBeAg inhibits duplication of HCV and decreases the expression of HCVcAg.

Fulminant Hepatic Failure Due to Hepatitis B Seroconversion Requiring Orthotopic Liver Transplantation

Purpose: Spontaneous Hepatitis Be antigen seroconversion (development of hepatitis Be antibody) can be associated with acute exacerbation of chronic hepatitis B virus (HBV)infection. The clinical spectrum of this exacerbation can vary from completely asymptomatic to typical symptoms of acute hepatitis to hepatic decompensation. We present a patient who developed fulminant hepatic failure (FHF)at the time of HBeAg seroconversion successfully treated with orthotopic liver transplantation (OLT). A 52 year old Caucasian female with PMH of HTN, ruptured cerebral aneurysm with right-sided hemiparesis and rheumatoid arthritis, but no known history of liver disease, presented with a 3-week history of abdominal pain, nausea, vomiting, and jaundice. Physical exam was remarkable for only jaundice, scleral icterus, diffuse abdominal tenderness, and lower extremities edema. Her labs showed ALT 304 U/L, AST 462 U/L, Alkaline phosphatase 209 U/L, bilirubin 6.1 mg/dl, (conjugated 3.6 mg/dl), and INR 2.4. The work up for the etiology of her liver disease was negative, except for hepatitis B. The HBV serology showed positive HBsAg, HBcIgM, HBeAb and negative HBeAg and HBsAb. Abdominal CT scan showed 15.2 cm liver without arterially enhancing lesions or biliary dilatation, patent hepatic vasculature and no ascites. Transjugular liver biopsy revealed extensive hepatic parenchymal extinction, severe activity (grade 4)and periportal fibrosis (stage 2). The stains for HBsAg and HBcAb were positive. The patient was started on Entecavir but developed hepatic encephalopathy in 2 days. At that point her total bilirubin was 10.1 mg/dl, INR 4.5, creatinine 0.6 mg/dl and MELD score 32. The patient was rapidly evaluated and listed as status 1 for OLT. She was transplanted 2 days later. After the OLT she was started on Tacrolimus, Mycophenolate mofetil, Hepatitis B immunoglobulin and continued on Entecavir. She had uncomplicated postoperative course and was discharged in 1 week. Her most recent HBV serology (4 months post OLT) showed HBsAb 682IU/L and HBV DNA less than 20 IU/ml. Most patients with chronic HBV infection eventually transition (either spontaneously or as a result of treatment)from immune-active phase to an inactive carrier state as they clear HBeAg and develop HBeAb (seroconversion). About 2/3 of the spontaneous seroconversions are preceded by hepatitis flare due to more robust immune clearance of the hepatocytes containing replicating HBV. In extreme cases this vigorous immune response can result in FHF. Even though HBV is the most common viral cause of FHF, it is not clear how often FHF is due to seroconversion and also what percentage of OLTs are done because of HBV seroconversion.

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

BackgroundHBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort.MethodsA retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression.ResultsA total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (p = 0. 038).ConclusionProlonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.

Long‐term effect of maternal HBeAg on delayed HBeAg seroconversion in offspring with chronic hepatitis B infection

This cohort study investigated the long-term effect of maternal hepatitis B virus (HBV) sero-status on the spontaneous HBeAg seroconversion in offspring with chronic HBV infection. A total of 185 HBeAg-positive chronic HBV-infected children, with maternal HBV seromarkers checked, were enrolled. The median age at enrolment and follow-up duration was 5.7 years (range, neonate to 16.5 years) and 20.2 years (range, 4.2-31.0 years) respectively. These children were grouped according to the initial maternal HBsAg and HBeAg status: (i) children of non-carrier mothers (n=48); (ii) children of HBeAg-negative chronic HBV-infected mothers (n=57); (iii) children of HBeAg-positive chronic HBV-infected mothers (n=80). HBV seromarkers and liver function profiles of these children were performed at 6-month intervals. One hundred and twenty-one (65.4%) subjects had achieved spontaneous HBeAg seroconversion at the end of this follow-up study. Spontaneous HBeAg seroconversion was achieved in 83.3% of children with non-carrier mothers, 73.7% of children with HBeAg-negative chronic HBV-infected mothers and 48.8% of children with HBeAg-positive mothers during similar duration (P<0.001). Positive maternal HBeAg and genotype C were associated with delayed spontaneous HBeAg seroconversion in multivariate analysis (P=0.01 and P=0.002 respectively). In children of HBeAg-positive chronic HBV-infected mothers, persistent presence of maternal HBeAg showed a trend of association with delayed HBeAg seroconversion in their offspring (P=0.06). Children of late maternal HBeAg seroconversion (>40 years old) had delayed HBeAg seroconversion compared with those of early HBeAg seroconversion mothers (P=0.06). Persistence of maternal HBeAg is an important risk factor for delayed spontaneous HBeAg seroconversion in children with chronic HBV infection.

Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B

Serum alanine transaminase (ALT), hepatitis B virus (HBV) DNA level and age are used in the evaluation of chronic hepatitis B (CHB). We designed this study to evaluate liver histology with ALT and its relation with age and HBV DNA. During the period of October 2006 to July 2009, 499 CHB patients were included in this study with detectable HBV DNA at PCR. Of these, 181 had normal ALT, 200 had ALT [>(1 × ULN) < (2 ULN)] and 118 had ALT ≥ 2 ULN and were labelled as Group 1, 2 and 3 respectively. A strong positive correlation was found between ALT and histological activity index (HAI) and fibrosis. However, 29 (52.7%) and five (9.1%) in Group 1 with positive HBeAg status had HAI ≥4 and fibrosis ≥2 respectively. Among those with HBeAg-negative status, 66 (23.1%) had HAI >4 and 31 (10.8%) had fibrosis ≥2. In Group 2, 14 (15.7%) had moderate-to-severe HAI and 19 (21.2%) had fibrosis ≥2 when HBeAg was positive, in those with HBeAg negative 34 (30.6%) had moderate-to-severe HAI and 38 (34.2%) had fibrosis ≥2. An ALT value of ≥58.5 U/l had higher sensitivity than that of 80 U/l in predicting significant histological changes. Further, HAI and fibrosis were significantly greater in the age of >30 years. We recommend liver biopsy in HBeAg-negative CHB over 30 years of age regardless of ALT level and starting treatment at ALT 1.5 × ULN instead of 2 × ULN.

HBc binds to the CpG islands of HBV cccDNA and promotes an epigenetic permissive state

HBV covalently closed circular DNA (cccDNA) is the template for the transcription of HBV. HBV core protein (HBc) is a main component of the HBV cccDNA minichromosome. However, the function of HBc in cccDNA is not fully understood. In light of recent findings that HBV cccDNA may be regulated epigenetically, we analyzed the binding of HBc to cccDNA and the impact of HBc on cccDNA epigenetic profile in the liver biopsy samples of 22 patients with chronic Hepatitis B (CHB). We found that HBc binding to HBV cccDNA occurred preferentially at CpG island 2, an important region for the regulation of HBV transcription. Furthermore, the relative abundances of HBc binding to CpG island 2 were positively correlated with the ratios of relaxed circular DNA to cccDNA and the levels of serum HBV DNA in those patients. Interestingly, the relative abundances of HBc binding to CpG island 2 were associated with the binding of CREB binding protein (CBP) and with hypomethylation in CpG island 2 of HBV cccDNA minichromosomes. However, relatively higher amounts of HBc binding to CpG island 2 of cccDNA were accompanied by lower amounts of HDAC1 binding. Multivariate analysis revealed that the abundances of HBc binding to CpG island 2 of cccDNA and positive HBeAg were independent factors associated with the replication of HBV (p = 0.001 for both). Apparently, HBc is a positive regulator of HBV transcription and replication, maintaining the permissive epigenetic state in the critical region of the HBV cccDNA minichromosomes.

A STUDY OF HEPATITIS B VIRUS GENOTYPES IN CHRONIC HEPATITIS B PATIENTS

Aims: To measure the prevalence of HBV genotypes in chronic hepatitis B patients and their relation to HBeAg and HBV DNA level. Methods: 81 patients were enrolled in this study from January 2009 to December 2010. Clinical, laboratory data were collected during the patient’s hospitalization. Sera were quantitatively tested for HBeAg and HBV DNA. HBV genotyping was made by real-time PCR. Results: Among the 81 patients, 60.5% had genotype B, 26.7% had genotype C and 8.6% had mixed genotype B-C. Prevalence of symptoms (fatigue, anorexia, insomnia...) was higher in genotype C than in genotype B. Genotype C patients had positivity higher HBeAg than genotype B patients (56% vs. 38,8%, p &lt;0.05). The rate of HBV DNA &gt; 107 copies/mL was higher in genotype C group than in genotype B group (36% vs. 28,6%, p &gt; 0.05). Conclusions: Most of the patients had genotypes B or C. Patients with genotype C had positive HBeAg and may be related to higher serological HBV DNA level than in genotype B.

HBV Surface Ag mutations in chronic carriers are rare in Baloochstan provinces of Iran: a community with a low rate of HBV-related cirrhosis and HCC

Background and Aims: The aim of this study was to determine the correlation between the hepatitis B virus surface Ag (HBsAg) genotypes and variations in the clinical/serological pictures among HBsAg positive chronic patients from South Khorasan province of Iran. Methods: Twenty-five patients were enrolled in this study. The HBs Ag gene was amplified and was directly sequenced. Genotypes and nucleotide/amino acid substitutions were characterized comparing with sequences obtained from the database. Results: All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Eight samples (group I) contained at least one mutation at the single amino acid level. Five out of 8 samples showed ALT levels above the normal range of which only one sample was anti-HBe positive. Group II (17 samples) did not contain any mutation, 4 were anti-HBe positive and 9 had increased ALT levels. In both groups, in anti-HBe positive patients who showed high levels of ALT, only one sample had amino acid mutations. Conversely, 7 of 20 samples with HBeAg positivity had mutations. In both groups, from a total of 18 amino acid mutations, 5 (27.5%) and 13 (72.5%) occurred in anti-HBe and HBeAg positive groups respectively. In general, there was no correlation between the occurrence of mutations and HBeAg status/ALT levels of the patients. Conclusion: The relatively small number of nucleotide/amino acid mutations might belong to either the initial phase (tolerant phase) of chronicity in our patients, regardless of being anti-HBe positive; or that even in anti-HBe positive phase in Iranian genotype D-infected patients, a somehow tolerant pattern due to the host genetic factors may be responsible.

Role of Serum Interleukin-10 Levels in Patients with Chronic Hepatitis B Virus Infection from India

© 2011, INASL 6 Intrafamilial Occurrence of Hepatitis B Virus Infection and the Profile of Liver Disease in Close Relatives of Patients with HBV Infection R Kavitha, TM Ramachandran, T Varghese DM Trainee and Presenting Author, Additional Professor, Professor, Department of Gastroenterology, Government Medical College, Calicut, Kerala Aim: To evaluate the occurrence of HBsAg positivity in family members of HBsAg positive patients and to evaluate the burden of liver disease in these family members. Materials and Methods: All HBsAg positive patients who attended Gastroenterology Department, Calicut Medical College from January 2009 to December 2010 were studied. They were evaluated with HBeAg, anti-HBeAb, HBV DNA, LFT and USG abdomen. All first-degree relatives and relatives staying in the same house were screened for HBsAg. The relatives who tested positive were evaluated for disease activity. Results: There were 376 index cases in total: 230 males and 146 females, M:F = 1.57:1. Mean age – 32.8 years (6–76 years). Ninety six (25.53%) patients did not turn up after the initial visit. Among the remaining 280 patients, 48 (17.14%) were HBeAg positive. 60.27% of females were detected during antenatal screening. One hundred and fifty three patients (54.64%) had abnormal LFT, 21 (7.5%) had acute hepatitis, 46 (16.43%) had cirrhosis and 10 (3.57%) had HCC. Complete family screening was done for 173 cases (61.8%). Among the cases whose family members were screened, 95 (54.91%) had at least one family member seropositive. A total of 1115 family members were screened of which 162 (14.53%) were HBsAg positive. The relatives affected were brothers (26.01%) and sisters (19.08%); mothers in 10.40%, fathers in 10.98%, sons in 6.08%, daughters in 1.35%, second-degree relatives in 5.78% and 4.72% of spouses. Affected family members had LFT abnormality in 31/43 (72.09%), cirrhosis in 9.3% (4/43), and HCC in 1 patient. 27.9% (12/43) cases were HBeAg positive. Forty seven (16.79%) index cases were reluctant for family screening. Conclusion: The occurrence of hepatitis B positivity in family members of HBsAg positive patients was 14.53% which is 28-fold more than the community prevalence of HBV infection in our population which was only 0.52%. Brothers and sisters were more affected. Hence the infection among siblings and parents may be due to horizontal transmission. Conflict of Interest: None Role of Serum Interleukin-10 Levels in Patients with Chronic Hepatitis B Virus Infection from India R Ruttalla, PK Gumma, SK Polipalli, VK Karra, P Kar Department of Medicine, Maulana Azad Medical College, University of Delhi, India Background/Aims: Cytokines play a significant role in immune defense and may play an important role in the pathogenesis of chronic hepatitis B. Patients with chronic hepatitis B infection were evaluated to determine whether serum interleukin-10 (IL-10) levels were changed and whether the degree of these changes in serum levels correlated with HBV DNA levels. Methodology: Twenty nine patients diagnosed with chronic hepatitis B, 20 inactive HBsAg carriers, 20 liver cirrhosis and 18 healthy controls without any hepatitis marker positivity were included in the study. Serum IL-10 levels were measured by using commercially available ELISA kits as per the manufacturer instruction [Ray Biotech, Norcross]. The associations between liver pathology and HBV DNA levels were assessed. Result: IL-10 is elevated more in liver cirrhosis with positive HBeAg in comparison to asymptomatic carrier and control. The IL-10 levels calculated were: cirrhosis (53.60 ± 52.10), CHB (51.90 ± 37.1), HbsAg carrier (32.27 ± 22.10) and healthy (50.01 ± 43.03) pg/mL. Conclusion: IL-10 production is increased in liver cirrhosis patients with HBeAg positivity as compared to other groups (p < 0.05). However, as IL-10 is increased in liver cirrhosis with HBeAg positivity, the HBe antigen may be responsible for the raised IL-10 levels. Conflict of Interest: None Oral Plenary Session Expression Analysis of Proteins Inducing Interferon in Chronic Hepatitis C Patients P Kar, PK Gumma, S Medhi PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India Background: In virus-infected cells, pattern recognition receptors (PRRs) like toll-like receptor (TLR)-3 and RIG-I recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β (TRIF) which through TRAF6 induce the interferon. 03_JCEH-Abstract.indd 6 3/18/2011 11:13:03 AM

Serum Neopterin Levels and Viral Load Among Hepatitis C Positive Recipients of Living Donor Renal Transplants

© 2011, INASL 4 Results: Of 74 patients screened, 48 patients included. (M:F = 22:26), mean age: 16–52 years median; 22 ± 9 years). Mean documented duration of viremia was 6 months to 12.5 years (median 6.23 ± 2 years). No correlation was observed between serum HBV DNA viral load and HBsAg titers (r = 0.32, p = 0.04) HBeAg positivity correlated with high viral load p = 0.03, r = 0.64), but not with HBsAg titers (p = 0.03, r = 0.34). SGPT has no correlation either with HBsAg titers (p = 0.02, r = 0.31) or viral load. Conclusion: There is no correlation between HBsAg titers and HBV DNA viral load in treatment naive chronic hepatitis B infection without cirrhosis. The contradiction of pretreatment absence of correlation between HBsAg titers and viral load and on treatment projected HBsAg titer correlation to treatment response needs to be addressed by further studies. Conflict of Interest: None Serum Neopterin Levels and Viral Load Among Hepatitis C Positive Recipients of Living Donor Renal Transplants S Justa, RW Minz, M Minz, S Anand, A Sharma Department of Immunopathology; Department of Renal Transplant Surgery; Post Graduate Institute of Medical Education and Research, Chandigarh, India Background and Aim: Neopterin belongs to the group of compounds known as pteridines. Increased concentration of neopterin has been reported in conditions causing stimulation of cellular immunity, such as viral infections and allograft rejection. The aim of this study was to assess the dynamics of serum neopterin during the first 6 months post transplantation among HCV-positive (group I) and negative (group II) recipients of living donor renal transplantation (LDRT). Methods: Twenty two group I and 10 group II patients were serially monitored for serum neopterin levels by ELISA. Group I patients were monitored at three time points i.e. pre-transplantation, day 10 and 6 months post-transplantation. Group II patients were monitored at two time points i.e. day 10 and 6 months post-transplantation. HCV serum viral load was monitored among group I patients by quantitative real time PCR. The histological changes occurring within the first 6 months post transplantation among the study groups were evaluated using Banff classification. Results: There was a significant increase in serum neopterin as well as neopterin to creatinine ratio on day 10 as well as 6-month posttransplantation in comparison to pre-transplantation levels among group I patients. Serum neopterin levels failed to show any association with either HCV viral load or allograft rejection. Conclusion: We did not find any association between neopterin and rejection episodes during the first 6 months post transplantation. Serum neopterin thus failed to delineate a low-risk population which might be spared invasive diagnostic procedures such as protocol biopsy. Nonetheless, our data suggests the use of serum neopterin levels as a possible, surrogate marker of cellular immune response to viral infection after transplantation. Conflict of Interest: None IL28b Genotype in HCV Infected Indian Subjects—A Preliminary Study SS Prasad*, PN Rao**, RM Mukherjee*, K Ashwini*, P Balkumar Reddy*, DN Reddy** *Asian Healthcare Foundation, **Asian Institute of Gastroenterology, Somajiguda, Hyderabad Introduction: It is well known that many patients will not be cured by standard treatment for HCV. A recent study reported that host IL28β polymorphism plays a significant role in clearance of HCV. Thus the present study is aimed to determine an association between host genotype and SVR in HCV patients. Materials and Methods: The study includes 38 patients, who are under standard treatment for HCV. A 3 mL of peripheral blood sample was processed for DNA isolation. PCR-direct sequencing method is employed for genotyping of IL28β polymorphism. The genotyping of HCV is done by reverse hybridization and quantification by RT-PCR. The project is approved by Institutional Ethics Committee and an informed consent was obtained from all the study patients. Results: The average age of patients was 51.6 years. Among them, 8 patients were females. A 21% (n = 8) of them are genotype 1, 42% (n = 16) genotype 2, 11% (n = 4) genotype 3 and for remaining viral genotype has not been done. The distribution of host genotype of IL28β polymorphism (rs129798760) as follows: CC genotype is observed in 74%, CT genotype is observed in 21%, TT genotype is observed in 5% of study patients. A total of 11 cases were discontinued for the treatment due to personal reasons and in 15 cases SVR results are awaited. However, 12 patients have completed the treatment and they were analyzed for the role of host genotype (IL28β) with SVR. Among these 03_JCEH-Abstract.indd 4 3/18/2011 11:13:03 AM

Correlates of poor perceived health among individuals living with HIV and HBV chronic infections: a longitudinal assessment

Chronic hepatitis B virus (HBV) infection affects up to 14% of people living with HIV and AIDS (PLWHA) and is associated with a higher risk of non-AIDS death. While great advances have been made in the therapeutic management of co-infection with HIV and HBV, nothing is known about perceived health in people living with HIV and HBV. This study aimed at characterizing individuals with poor perceived overall health among 308 HIV–HBV co-infected individuals enrolled between May 2002 and May 2003 in a three-year French cohort. A binary score for perceived overall health (good vs. poor) was calculated from individuals’ responses to the COOP-WONCA charts at cohort enrolment and at quarterly visits throughout the follow-up. Mixed models were used to explore factors associated with this score. At enrolment, 190 individuals (62%) reported poor overall health. In the multivariate analysis, low CD4 percentage, co-infection with hepatitis C or D viruses, HIV diagnosis before 1996 and HBeAg positivity were independently associated with poor perceived overall health. Poor perceived health concerns a considerable portion of individuals living with HIV and HBV. Individuals with wild-type HBV and multiple hepatitis infection require better clinical management. Further research is needed for hepatitis D virus infection, for which treatment options are currently very limited.

Management and treatment of chronic hepatitis B virus infection in HIV positive and negative patients: The EPIB 2008 study

To compare the management and the virological and serological efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative patients. Two hundred and forty-six HIV positive and 205 HIV negative consecutive patients with past or present CHB, seen in October 2008 in participating departments, were included in a multicenter study. All the data were retrospectively collected from the first visit to October 2008 through a standardized questionnaire. Compared to HIV negative patients, HIV positive patients more often presented positive HBeAg (46.4% vs. 32.8%, p=0.01), HBV genotype A (54.8% vs. 17.1%, p<0.0001), co-infection with HCV (12.4% vs. 5.9%, p=0.0002) or HDV (12.6% vs. 2.9%, p=0.04). HIV positive patients were more often on HBV therapy (92.7% vs. 57.1%, p<0.0001), leading to undetectable serum HBV DNA levels (71.0% vs. 44.1%, p<0.0001). In HIV positive patients, multivariate analysis showed that older age, lower initial HBV DNA levels, and longer time on HBV therapy significantly correlated with undetectable HBV DNA. No difference in efficacy was observed between tenofovir used alone or in combination. HBsAg (but not HBe) loss was more often observed in HIV positive patients, sometimes followed by HBsAg re-appearance after withdrawal of HBV treatment. Excluding the 37 HBV-HCV-co-infected patients, the last clinical presentation and liver fibrosis scores were similar in HIV positive and negative patients. The assessment of CHB and the efficacy of HBV therapy have improved in HIV positive patients. HIV infection did not have a negative impact on the likelihood of HBV therapeutic success.

Reactivation of latent viral hepatitis infection in patients of chronic myeloid leukemia treated with imatinib mesylate: Experience from a tertiary cancer center in India.

6593 Background: Imatinib mesylate (IM) is considered standard first-line therapy for patients with chronic myeloid leukemia (CML). Reactivation of hepatitis B virus (HBV) and hepatitis C (HCV) virus infection is a well known complication for patients with latent infection who are being treated with cytotoxic or immunosuppressive therapy. However, it is still unclear whether IM induces the reactivation of HBV and HCV in patients with a latent infection. Methods: We analyzed 1,100 patients of CML treated with IM. All patients were screened at the start of therapy by Enzyme linked Immuno Sorbent Assay (ELISA) for hepatitis B and C virus. These patients were prospectively followed up for viral reactivation. Results: Twenty-five patients were found to be positive for latent HBV (16 patients: 13 males, 3 females) and HCV (9 patients: 6 males, 3 females) infection at baseline evaluation (prevalence of 2.54%). No patient confirmed past history of jaundice or blood transfusion. All patients had normal liver function tests (LFTs) at baseline. Median follow-up of these patients was 33 months (range 6-67 months). None of these patients developed altered LFTs on follow-up while IM was continued. Importantly, no viral reactivation was seen in any of these patients. However, 3 patients who were initially negative for viral hepatitis markers, had seroconversion for hepatitis B virus (mean time 10 months). Out of these, LFTs were deranged in two patients, of which 1 patient developed acute hepatitis B. (Patient was symptomatic with raised viral DNA copies by PCR and positive HBe antigen by ELISA).This patient was treated with lamivudine following which patient had complete recovery and LFTs gradually normalized. This patient did not have subsequent flare of viral hepatitis on IM. Conclusions: Though the prevalence of viral hepatitis in CML in this study is same as seen in general population in India, the reactivation of this infection is not a common phenomenon. Imatinib can be safely continued in these CML patients without concern of increased risk of viral reactivation or alteration of liver functions. No significant financial relationships to disclose.

636 High Rate of Complete Viral Suppression With Combination Therapy With Tenofovir Using Entecavir or Lamivudine/Emtricitabine in Patients With Chronic Hepatitis B and Prior Monotherapy Failure

PURPOSE: Combination therapy for chronic hepatitis B (CHB) is recommended for patients with antiviral resistance or partial response to prior monotherapy, but outcomes of combination therapy in this setting is limited. Our goal was to examine the complete viral suppression (CVS) rate for combination therapy with tenofovir+entecavir (TDF+ETV) or TDF+lamivudine or emtricitabine (TDF+LAM/FTC) in patients with CHB who failed prior monotherapy. METHODS: We retrospectively studied 27 consecutive patients with either viral resistance or partial response to CHB monotherapy who were evaluated at 3 gastroenterology and liver clinics in the U.S. and began treatment with combination therapy as follows: TDF+ETV (n= 16) and TDF+LAM/FTC (n=11). CVS was defined as undetectable HBV DNA PCR (<100160 copies/mL). RESULTS: All patients were Asian and most were male (67%) with a median age of 48 (26-75). All patients had genotypes B or C and 56% had positive HBeAg. Median HBV DNA at the time of initiation of combination therapy was 3.8 (1.4-7.2) log10IU/mL. Indications for TDF-based combination therapy were antiviral resistance (52%) and partial response (48%) with monotherapy. Antiviral resistance included resistance to LAM (64%), adefovir (ADV) (21%), and LAM and ETV (14%). Immediate monotherapy prior to combination therapy were LAM (4%), ADV (26%), and ETV (70%). Median duration of monotherapy was 20 (1-84) months. The majority (22 of 27 patients or 78%) of the total cohort achieved CVS by 6 months and maintained CVS for a median follow-up of 20 months. More patients in the TDF+ETV group achieved CVS at 6 months (86% vs. 67%), but all 3 TDF+LAM/ FTC patients who were still viremic at 6 months achieved CVS at 12 months. The 12-month follow-up of the other 2 patients who were viremic at 6 months and on TDF+ETV is still pending. There were no significant differences in CVS rate between the antiviral resistance and partial responder groups at 6 or 12 months. No HBeAg seroconversion or development of new antiviral resistance was observed. CONCLUSION: Most patients with CHB who had antiviral resistance or partial response to monotherapy achieved CVS by 6 months using TDF-based combination therapy. CVS rate appears higher at 6 months in TDF+ETV compared to TDF+LAM/FTC, but this difference did not persist as all patients on TDF+LAM/FTC achieved CVS at 12-month follow-up.