HBsAg Titer Research Articles

Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs

Background and objectiveThe aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. Study designWe analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. ResultsHBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. ConclusionsIn HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12–18 months of follow up. HBs seroconversion was observed in two patients.

Viral factors and outcome of chronic hepatitis B revisited.

Virus-host interactions during chronic hepatitis B virus (HBV) infection allow the distinction of several phases, defined according to virological, biochemical and histological profiles: immune-tolerant (IT) [HBeAg-positive, very high serum level of HBV DNA, normal serum alanine aminotransferase (ALT) level without significant liver necroinflammation activity and fibrosis], immune-reactive (HBeAg-positive, high HBV DNA and ALT levels with moderate to severe liver activity and fibrosis) and the inactive carrier state, which follows HBeAg seroconversion and reflects host immune control of the HBV infection (HBeAg-negative, low HBV DNA level, normal ALT level without liver damage in most cases). An HBeAg-negative chronic hepatitis B (CHB) phase (HBeAg-negative, HBV DNA level above 2,000–20,000 IU/mL, normal/high ALT level and histological signs of CHB) occurs in patients who have achieved HBeAg seroconversion or in inactive carriers due to HBV reactivation [1]. Basal core promoter (BCP) mutations have been reported to possibly modulate HBV replication [2–4] and could thus impact the natural course of CHB. In addition, BCP mutations (the more common are the BCP A1762T/G1764A dual mutations) and precore G1896A mutation lead to the impairment and abolishment, respectively, of HBeAg production [5], and they have been reported in patients with HBeAg-negative CHB occurring under immune pressure to control HBV infection. Importantly, the more common BCP dual mutations have been shown to increase the risk of developing hepatocellular carcinoma (HCC) [6, 7]. Turyadi et al. [8] carried out a cross-sectional study to characterize the relationships between viral factors and the natural history of CHB within the Indonesian population. In their study, Turyadi et al. assessed the correlations between viral parameters [serum HBsAg, HBeAg and HBV DNA levels, HBV genotype and BCP (A1762T/G1764A)/ precore (G1896A) mutations] in different stages of HBV infection within a cohort of 152 treatment-naive Indonesian patients. Patients were categorized into the four phases of CHB, denoted IT, immune-clearance (IC, i.e, immunereactive phase), low/non-replicative (LR, i.e., inactive carrier state) and HBeAg-negative CHB (ENH). The authors showed that HBsAg and HBV DNA serum levels were both at a high level and strongly correlated in the early phases of CHB (i.e., IT and IC), but a tendency to separate from one another occurred after HBeAg seroconversion. A moderate correlation between serum HBV DNA and serum HBsAg titers was found in the ENH phase, and no correlation was observed in the LR phase. These important results are consistent with previous studies [9, 10] and suggest that the control of HBV replication by the immune system does not hamper HBsAg production. In this study, a temporal relationship between HBeAg seroconversion and an increase of prevalence of patients with This is an editorial to the article available at doi:10.1007/s12072-0139438-z

433 QUANTIFICATION OF LARGE, MIDDLE AND SMALL HEPATITIS B VIRUS (HBV) SURFACE PROTEIN (HBsAg) FRACTIONS IN PATIENTS WITH ACUTE HEPATITIS B

Methods: 315 HBsAg positive mothers and their offspring received combined immunoprophylaxis (hepatitis B immune globulin and hepatitis B vaccine) were recruited in this study. The venous blood of 315 mothers and infants (315 at birth, 262 at 1-month-old and 251 at 7-month-old) was collected for tests of HBVDNA load and HBV markers titer. Result: The positive rates of HBVDNA, HBsAg and HBeAg in the newborns at birth were 17.8% (56/315), 25.1% (79/315) and 25.4% (80/315), respectively. Maternal HBVDNA load, HBsAg and HBeAg titer were associated with neonatal HBVDNA load, HBsAg and HBeAg titer at birth respectively. In the neonatus born to the pregnant mothers with HBVDNA>10 IU/ml, HBsAg>10 IU/ml and HBeAg>1 s/co, the probability of HBVDNA-, HBsAgand HBeAgpositive at birth significantly increased (areas under ORC curve were the largest, 0.770, 0.697 and 0.944, respectively). During the follow-up, the positive rates of HBVDNA, HBsAg and HBeAg in infants reduced gradually and HBVDNA (83.9%), HBsAg (87.3%) and HBeAg (87.5%) in the majority of infants turned to be negative at 7 months after birth, while 3.6% (9/251) infants became chronic HBV carriers (HBVDNAand HBsAg-positive from birth to 7-monthold) and 8.6% (18/242) were non-responders (anti-HBs <10mIU/ml at 7-month-old). High levels of HBsAg titer and HBVDNA load of newborns at birth were associated with chronic HBV infection, while the relevance between HBsAg, HBeAg and HBVDNA from mother to infant and the non-response to HB vaccination was uncertain. Conclusion: HBsAg and HBVDNA, as HBeAg, could cross the human placenta from mother to infant and lead to short-term antigenemia or virusemia in newborns, while HBsAgand HBVDNA-positive at birth may not be indication for HBV infection of infants. HBVDNA, HBsAg and HBeAg from mother to infant did not contribute to the non-response to HB vaccination, while further follow-up was still in need.

Correlation Between Quantitative HBsAg and HBV-DNA in Chronic Hepatitis B Infection

Background : Methods used to diagnose and monitor chronic hepatitis B (CHB) by quantitation of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) levels is expensive. Cheaper laboratory test as an additional marker is needed, thus we studied serum quantitative HBsAg to be used as surrogate marker in CHB patients. This study was aimed to investigate correlation between serum quantitative HBsAg and HBV-DNA in CHB patients. Method : In this cross-sectional study, we enrolled 62 CHB patients between January 2010 and December 2012 who had quantitative HBsAg and HBV-DNA assays in a private laboratory at Denpasar. HBV-DNA was measured by real-time polymerase chain reaction and quantitative serum HBsAg was measured by chemiluminescent microparticle immunoassay (CMIA). Stastistical analysis was performed by Mann-Whitney and Spearman’s correlation. Results : Of 62 patients, most subjects were males (82.26%). Mean HBsAg titer of CHB in HBeAg positive and negative patients were 281,000 and 4,900 IU/mL, respectively; while mean HBV-DNA in HBeAg positive and negative patients were 59,000,000 and 7,530,000 IU/mL, respectively. We found that quantitative HBsAg and HBV-DNA in HBeAg positive and HBeAg negative patients were statistically signi cant (p = 0.0001, p = 0.0001, respectively). Signi cant correlation was found between serum quantitative HBsAg and HBV-DNA (r = 0.737; p= 0.000). Quantitative HBsAg was signi cantly correlated with HBV-DNA in HBeAg-positive subgroup (r = 0.717; p = 0.0001); and signi cant correlation was also found in HBeAg-negative subgroup (r = 0.443; p = 0.006) although the correlation was weak. Conclusion : Quantitative HBsAg has signi cant correlation with HBV-DNA in CHB patients. Keywords : quantitative HBsAg Assay, HBV-DNA, HBeAg, chronic hepatitis B infection

Kinetics and prediction of HBsAg loss during therapy with analogues in patients affected by chronic hepatitis B HBeAg negative and genotype D

In patients affected by chronic hepatitis because of HBV infection, long-term suppressive therapy with nucleos(t)ides analogues in the HBeAg- patients has shown low effects on HBsAg titre (qHBsAg) decrease, and HBsAg loss is difficult to achieve. Thus, in this type of patients the main goals of antiviral therapy is the suppression of HBV-DNA and ALT normalization. We retrospectively evaluated different qHBsAg kinetics in 134 treatment-naïve patients having the same characteristics: HBeAg-, infection sustained by HBV genotype D and persistently undetectable HBV-DNA. Patients were treated with NAs therapy (lamivudine, adefovir, telbivudine, entecavir and tenofovir) for at least 2years. qHBsAg was performed every 6months. Our results showed a significantly greater qHBsAg decline after 2years in patients treated with tenofovir (0.45 logIU/ml) than in patients treated with telbivudine (0.12 logIU/ml; P<0.001). The calculated expected time to HBsAg loss was shorter in the tenofovir group than in the telbivudine group (nearly 17 vs 63years, P<0.001). HBeAg negative patients infected by HBV genotype D should be treated with more potent NAs such as entecavir or tenofovir to obtain a significant qHBsAg decrease, but the achievement of HBsAg loss seems to require almost two decades of therapy.

Correlation between Hepatitis B surface antigen titers and HBV DNA levels

Background/Aim:To assess the correlation between serum HBsAg titers and hepatitis B virus (HBV) DNA levels in patients with hepatitis B envelop antigen-negative (HBeAg −ve) HBV genotype-D (HBV/D) infection.Patients and Methods:A total of 106 treatment- naïve, HBeAg −ve HBV/D patients were included; 78 in the inactive carrier (IC) state and 28 in the active hepatitis (AH) stage. HBV DNA load and HBsAg titers were tested using TaqMan real-time polymerase chain reaction (PCR) and automated chemiluminescent microparticle immunoassay, respectively.Results:The median (range) log10 HBsAg titer was significantly lower in the IC group compared with AH group, 3.09 (−1 to –4.4) versus 3.68 (−0.77 to 5.09) IU/mL, respectively; P < 0.001. The suggested cutoff value of HBsAg titer to differentiate between the two groups was 3.79 log10 IU/mL. In addition, there was a significant positive correlation between HBsAg and HBV DNA levels in the whole cohort, AH, and IC groups (r = 0.6, P < 0.0001; r = 0.591, P = 0.001; and r = 0.243, P = 0.032, respectively).Conclusion:Serum HBsAg titers may correlate with HBV DNA in treatment-naïve HBeAg –ve HBV/D patients, and supports the use of HBsAg levels in clinical practice as a predictor of serum HBV DNA levels.

Hepatitis viral load testing: what does it all mean?

The availability of assays for quantification of HBV DNA and HBsAg has resulted in a surge of research redefining the natural history of chronic hepatitis B (CHB) and the effects of specific antiviral therapy on levels of these viral markers. Assessment of on-treatment changes in HBsAg titre has provided new management algorithms to achieve the endpoint of HBsAg seroconversion. As with chronic hepatitis C management, response guided therapy (RGT) has arrived for hepatitis B. specific antiviral therapy has been available for hepatitis B for over a decade, and is now becoming available for hepatitis C. There are a number of direct acting antivirals (DAA) for hepatitis C and these should quickly replace the current standard of care of pegylated IFN and ribavirin, and the need for complex testing algorithms using HCV RNA and RGT (including stopping rules). Not only has molecular diagnostics emerged as an important tool for measuring viral load and burden, response to therapy as well as staging of disease, but is also useful for defining emergence of antiviral drug resistance. These viral load and molecular assays actually simplify patient management and monitoring for all concerned.

Prediction of the Response to Pegylated Interferon α-2a in Patients with HBeAg Positive Chronic Hepatitis B through Decline of Serum HBV DNA and Hepatitis B Virus Surface Antigen at Week 4

Abstract Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon (PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week (r = 0.8202, P &lt; 0.0001 and r = 0.6838, P &lt; 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week (r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week (r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.

A predictive value of quantitative HBsAg for serum HBV DNA level among HBeAg-positive pregnant women

BackgroundThe high maternal HBV DNA level is the most important factor contributing to HBV perinatal transmission. This study is to explore whether HBsAg can be used as a surrogate marker of serum HBV DNA for HBsAg-positive pregnant women. MethodsA total of 975 HBsAg-positive pregnant women and their infants were enrolled in this study. All infants received three doses of a yeast-derived recombinant Hepatitis B vaccine at 0, 1 and 6months. They were also given Hepatitis B immunoglobulin (HBIG) at birth. HBsAg and HBeAg were determined using Abbott Architect assays while serum HBV DNA level was detected by the Abbott Real Time HBV DNA assay. ResultsOf the 975 subjects, 367 (37.6%) were HBeAg-positive and 608 (62.4%) were HBeAg-negative. Among the HBeAg-positive group, the samples with HBV DNA levels of ≥7.0logIU/mL were 76.6% (281/367), and it was only 0.7% (4/608) for the HBeAg-negative group. HBV DNA level was positively correlated with HBsAg in HBeAg-positive group (r=0.786, p<0.001) but not in HBeAg-negative group (r=0.022, p=0.593). Among HBeAg-positive group, the area under the receiver–operator curve (ROC) of HBsAg titer for high HBV DNA level (≥7.0logIU/mL) was 0.961 (95% CI, 0.940–0.983, p<0.001). The optimum cut-off point HBsAg titer above 4.1logIU/mL had a sensitivity of 85.1%, specificity of 96.5%, and accuracy of 87.5% to predict HBV DNA levels of ≥7.0logIU/mL. Of 367 infants born to mothers with HBeAg-positive, perinatal transmission was detected in 24 infants (6.5%, 24/367). Their mothers all had serum HBV DNA levels of ≥7.0logIU/mL, 23 (95.8%) had HBsAg titers of ≥4.1logIU/mL and the other mother had HBsAg titer of 3.9logIU/mL. Of 608 infants born to mothers with HBeAg-negative, only one (0.2%, 1/608) became HBsAg-positive at the age of 7months, and the mother of the infant had serum HBV DNA level of 3.4logIU/mL and HBsAg titer of 1.8logIU/mL, respectively. ConclusionSerum HBsAg titer may be used as a surrogate marker of serum HBV DNA for HBeAg-positive pregnant women.

Is there an association between the measurement of qualitative HBsAg and virologic response in chronic HBV infection?

Background. In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection.Material and methods. A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD.Results. Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups.Conclusion. In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.

A comparison of clevudine and entecavir for treatment-naïve patients with chronic hepatitis B: results after 2years of treatment.

This study was undertaken to compare the efficacy, safety, and resistance profile of clevudine (CLV) and entecavir (ETV) following a 2-year treatment period. One hundred and eight Korean patients from the prior 48-week study were followed with continuous therapy for up to 2years and monitored for hepatitis B virus (HBV) DNA levels, HBeAg seroconversion, serum ALT, emergence of drug-resistant mutant HBV, and drug-related adverse events. A complete virological response during the 2-year treatment period occurred in 68.0% in the CLV group and in 84.5% in the ETV group (p=0.043). The cumulative percentage of patients with sustained virological responses at 2years was 54.0 and 77.6% in the CLV and ETV group, respectively (p=0.010). Virological breakthrough occurred in 12 patients in the CLV group; however, there were none in the ETV group (p<0.001). HBeAg seroconversion rates were not different between the two groups. In patients who maintained sustained virological responses at 2years, the mean reduction in HBsAg titer was -0.24 and -0.06logIU/ml in the CLV and ETV group, respectively (p>0.05). Clinical myopathy occurred in seven patients in the CLV group; however, this was not observed in the ETV group (p=0.004). ETV was associated with a significantly higher virological response rate than CLV at 2years. ETV was superior to CLV in terms of the drug resistance profile and the development of clinical myopathy. Further studies to see whether the unique characteristic of CLV to reduce HBsAg titer is associated with the removal of ccc-DNA from hepatocytes and the remission of the disease are needed.

531 TENOFOVIR DF TREATMENT IS SAFE AND WELL TOLERATED IN CHRONIC HEPATITIS B (CHB) PATIENTS WITH BASELINE DECREASED GLOMERULAR FILTRATION RATE

(W+24). Sustained virological response (SVR) defined as HBV-DNA 2000 IU/ml was observed in 24 patients 19/24 were non responders (NPV: 79%). A decline in HBsAg titer 10% at week 12 and week 24, respectively. Conclusions: In patients receiving PEG-IFN plus tenofovir, a SVR was observed in 30% and an HBsAg loss in 11%. Baseline HBsAg titer was predictive of: ≤2000 IU/ml HBsAg loss (100%) and SVR (PPV 50%); >2000 IU/ml non-response (NPV 80%). A lack of ≥10% decline in HBsAg level at week 12 or week 24 allows identifying non-responders with a high NPV 80%. An early (week 12) HBsAg level decline is associated with HBsAg loss.

530 HIGH EFFICACY AND SAFETY OF TENOFOVIR DF IN 441 NAIVE AND NUC-EXPERIENCED CHRONIC HEPATITIS B PATIENTS: A REAL LIFE MULTICENTER PROSPECTIVE COHORT STUDY

(W+24). Sustained virological response (SVR) defined as HBV-DNA 2000 IU/ml was observed in 24 patients 19/24 were non responders (NPV: 79%). A decline in HBsAg titer 10% at week 12 and week 24, respectively. Conclusions: In patients receiving PEG-IFN plus tenofovir, a SVR was observed in 30% and an HBsAg loss in 11%. Baseline HBsAg titer was predictive of: ≤2000 IU/ml HBsAg loss (100%) and SVR (PPV 50%); >2000 IU/ml non-response (NPV 80%). A lack of ≥10% decline in HBsAg level at week 12 or week 24 allows identifying non-responders with a high NPV 80%. An early (week 12) HBsAg level decline is associated with HBsAg loss.

Interleukin‐15 suppresses hepatitis B virus replication via IFN‐β production in a C57BL/6 mouse model

Interleukin-15 (IL-15) is a pleiotropic cytokine known to modulate both innate and adaptive immunity. It is suggested that IL-15 may play an important role in the regulation of immune response to hepatitis B virus (HBV). We investigated whether IL-15 could modulate the immune response to HBV. A mouse model for HBV tolerance was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. This HBV-carrier mouse was simultaneously hydrodynamically injected with either an IL-15-expression plasmid pLIVE-IL-15 or a mock control vector pLIVE-EGFP. The serum levels of HBsAg and HBeAg were measured by radioimmunoassay. Hydrodynamic injection of the plasmid pLIVE-IL-15 resulted in sustained high level of IL-15 in mouse serum, along with the markedly decreased serum HBsAg and HBeAg titres and liver HBV DNA levels. IL-15 also induced anti-HBV activity in T cell- and B cell-deficient Rag1(-/-) mice. Interestingly, despite an increase in NK cell numbers in both spleen and liver of IL-15 treated mice, the anti-HBV effect of IL-15 was neither dependent on presence of NK cells nor on production of IFN-γ. Furthermore, IL-15 could exert anti-HBV function independent of the common IL-2γ(c) R. Lastly, we found that IFN-β expression in the liver and serum was significantly up-regulated by liver expression of IL-15, and blockade of IFN-β function abrogated the anti-HBV activity of IL-15. Liver over-expression of IL-15 may suppress HBV replication in an IFN-β-dependent manner.

Hepatitis B serology and vaccinations are infrequently assessed in IBD patients receiving TNF-a inhibitors

TNF-α inhibitors are important agents in the treatment of inflammatory bowel disease (IBD) patients. Individuals requiring TNF-α inhibitors are at increased risk for development of severe hepatitis B infection when immunosuppressed. There are numerous reports of significant morbidity and mortality associated with hepatitis B infections in patients receiving TNF-α inhibitors. It is recommended that all patients receiving TNF-α inhibitors have hepatitis B serology obtained and be immunized if appropriate. This study evaluated the frequency at which hepatitis B serology and vaccination status was obtained in IBD patients receiving TNF-α inhibitors at an urban university medical center. The medical records of all IBD patients on infliximab (Remicade), adalimumab (Humira), and certolizumab (Cemzia) at an IBD program in an urban university medical center were evaluated. There were no exclusion criteria. Patient age, race, gender, disease type (Crohn's Disease or Ulcerative Colitis), type of TNF-α inhibitor, hepatitis B antigen (HBsAg), hepatitis B antibody (HBsAb), and hepatitis B vaccination status were recorded. A database, maintaining patient confidentiality, was created using Microsoft Excel. Statistical analysis was performed using a Fisher Exact Test with significance set at P < 0.05. Medical records of 44 patients were reviewed. There were 21 females (48%) and 23 males (52%) with a mean age of 36 years (range 19-75 years). 35 patients were diagnosed with Crohn's disease (79.5%), 8 patients with ulcerative colitis (18.2%), and 1 indeterminate colitis (2.3%). 30 patients were on infliximab (68%), 14 on adalimumab (32%), and none were on certolizumab. Of the total study population 25 (57%) had documented HBsAg titer results prior to initiating therapy with no patients having positive results. There were no differences in screening based on gender (p = 0.76), disease type (p = 1.0), or drug therapy (p = 0.10). HBsAb serologies were documented in 12 patients (27%) of which 8 were positive (18%) and 4 were negative (9%). Only 1 patient had prior documentation of HBV vaccination, and no vaccinations were administered prior to or during TNF-α inhibitor therapy. The mean age for the HBsAb positive group was 24.7 years and 40.1 years for the negative group. There were no appreciable differences in HBsAb screening between gender (p = 1) or disease type (p = 0.617). There was however, significantly less HBsAb screening (p = 0.025) in patients on adalimumab with 93% undocumented compared to 67% of those on infliximab. Hepatitis B virus serologies and vaccination status are inconsistently checked before initiating treatment with TNF-α inhibitors. It is unclear why adalimumab compared to infliximab had even lower assessment frequencies. The small sample size, single-institution, and retrospective design of this study may limit the ability to extrapolate the results. However, the low incidence of hepatitis B virus serology documentation despite the known dangers suggests the need for increased awareness of virus risk and the administration of vaccination when appropriate in IBD patients on TNF-α inhibitors.

The discrepancy of HBsAg titre and HBV DNA in patients with chronic hepatitis B, HBV-related liver cirrhosis and hepatocellular carcinoma

To investigate the discrepancy of HBsAg titre and correlation of HBV DNA levels among patients with chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBsAg titre and HBV DNA in serum samples were measured among 47 CHB, 72 LC and 54 HCC cases using Abbott chemiluminescence and fluorescence quantitative PCR, respectively. Statistical analyses among multiple groups, between two groups and about the correlation were performed using Kruskal-Wallis test, Mann-Whitney U test and Spearman test, respectively. The median HBsAg titre level in serum samples decreased from 2361.10 IU/ml in CHB cohort to 1001.64 IU/ml in LC cohort and 594.35 IU/ml in HCC cohort, suggesting a statistically significant difference (x2 = 24.394, P less than 0.05). Moreover, HBsAg titre in CHB group was significantly higher than that in LC group ( Z = -3.754, P less than 0.05). CHB patients had significantly higher HBsAg titre than HCC cases ( Z = -4.630, P less than 0.05). However, there was no statistically significant difference in HBsAg titre between LC and HCC group. Among HBeAg positive patients, HBsAg titre decreased from 3259.83 IU/ml in CHB group to 1077.30 IU/ml in LC group and 789.72 IU/ml in HCC group, indicating a significant difference (x2 = 15.643, P less than 0.01). Among HBeAg negative patients, HBsAg titre declined from 1669.00 IU/ml in CHB group to 1001.64 IU/ml in LC group and 582.05 IU/ml in HCC group, suggesting of a significant difference (x2 = 6.423, P less than 0.05). Positive correlation between HBsAg titre and HBV DNA was found in CHB ( r = 0.297, P less than 0.05), LC (r = 0.346, P less than 0.05) and HCC (r = 0.452, P less than 0.05), respectively. HBsAg titre level in serum decreased progressively from CHB to LC and HCC group. There were positive correlations between HBsAg titre and HBV DNA level in CHB, LC and HCC.

The change of the quantitative HBsAg level during the natural course of chronic hepatitis B

There is insufficient information about HBsAg levels and their correlation with serum hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB). We aimed to describe HBsAg levels during various phases of CHB and to investigate the correlation with serum HBV DNA levels. A total of 645 treatment-naïve Korean CHB patients were included in this retrospective cross-sectional study. They were categorized into immune tolerance (IT, n=56), HBeAg-positive hepatitis (EPH, n=150), inactive carrier (IC, n=274) and HBeAg-negative hepatitis (ENH, n=165). The baseline HBsAg and HBV DNA levels were measured. The mean HBsAg titres (log IU/ml) differed (P<0.001): IT 4.29, EPH 3.64, IC 2.05 and ENH 3.23. In 645 patients, HBsAg and HBV DNA showed a significant correlation (r=0.693, P<0.001), and this was also observed in the IT, EPH and IC groups (r=0.664, r=0.541, r=0.505, respectively, all P<0.001), but not in the ENH group (r=0.093, P=0.321). Age had a negative correlation with HBsAg (r=-0.451, P<0.001). The cirrhotic patients had a significantly lower HBsAg level than the non-cirrhotic patients (2.41 ± 1.36 vs. 3.02 ± 1.21 log IU/ml, P<0.001). The HBsAg level varied significantly in different phases of CHB and was correlated with HBV DNA during the IT, EPH and IC phases. These findings can provide additional information to understand the natural course and pathogenesis of CHB.

English

&nbsp; Hepatitis D is the important complication in cirrhotic patients. Diagnosis of hepatitis D is based on detection of HBSAg and HDV Ab titer determination. The present research was performed on a number of cirrhotic patients with the aim to assess the prevalence of hepatitis D and B. In present study all the cirrhotic patients who were referred to Gastroenterology and Endoscopy ward of Imam Khomeini hospital during a period of 18 months were included. The level of anti HDV Ab, anti HBS Ab and HBS Ag were determined by method of ELISA (Pishtaz Teb). In this study 60 cirrhotic patients were evaluated. 16 patients were HBS Ag positive with mean age of 51.9 years, and from this group, 13 patients were anti HBC positive with mean age of 53.23 years and from this group, 8 patients were HDV Ab positive with mean age of 49 years. Hepatitis D remains as one of the problems in developing countries. By timely screening of cirrhotic patients for HDV, patients could undergo additional treatments. &nbsp; Key words:&nbsp;Liver cirrhosis, hepatitis D, hepatitis B, HBS Ag, HBC Ab, HDV Ab.

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

Natural history of chronic HBV infection: special emphasis on the prognostic implications of the inactive carrier state versus chronic hepatitis

The evaluation of the natural history of chronic hepatitis B virus (HBV) infection requires the precise definition of the various clinical conditions that can be encountered (i.e. inactive carrier state or subject with liver disease activity). This can be achieved by repeat monitoring of ALT, serum HBV-DNA levels (over a period of at least 1 year, according to international guidelines) and/or evaluation of HBsAg titre. Liver biopsy may offer additional information although it is not mandatory. Overall, the natural history of the true inactive carrier is benign: reactivation of hepatitis, especially in Western countries, is rare and is usually due to co-factors (like alcohol or drugs); spontaneous HBsAg loss is frequent (around 1% per year) and HCC development rare. On the other hand, in patients with chronic hepatitis B or cirrhosis, the risk of reactivation, of HCC development and of liver-related mortality is much higher, especially in Eastern countries, and should therefore lead to antiviral therapy.