HBsAg Loss In Patients Research Articles

Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B

HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNαtreatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of invitro and invivo experiments. GWAS results indicated a significant association between the rs7519753C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p= 4.85× 10-8, odds ratio= 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753C allele (p= 2.90× 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p= 0.035). Invitro and invivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. The rs7519753C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.

SAT-148 - Low HBV DNA and HBsAg levels at 24 weeks off-treatment predict sustained response and HBsAg loss in patients who discontinued antiviral therapy

SAT-148 - Low HBV DNA and HBsAg levels at 24 weeks off-treatment predict sustained response and HBsAg loss in patients who discontinued antiviral therapy

Loss of HBsAg in Patients with High Levels of HBV-DNA During Treatment with Nucleoside or Nucleotide Analogs

Background: HBsAg is synthesized in the endoplasmic reticulum and is necessary for the formation of complete HBV particles. A decreased synthesis of this antigen leads to an intracellular inhibition of virus production. Methods: The study aimed to assess the incidence of HBsAg elimination among 1,290 patients who suffered from chronic HBV infection undergoing an antiviral treatment with nucleoside or nucleotide analogs (NAs). Furthermore, possible predictive factors for this elimination were analyzed. Results: A permanent HBsAg loss was confirmed in 3% of the patients, which was more frequent in men than in women (4.4% vs. 1.9%; P = 0.009). The HBsAg elimination occurred in 5% of HBeAg (+) patients and 2.8% of HBeAg (-) patients. The age of patients whose HBsAg was eliminated was higher than the age of the remaining patients (60 vs. 51 y/o). The effect of initially used pegylated interferon alfa (PEG-IFN) therapy on the HBsAg elimination was not observed. It occurred with the use of entecavir (ETV) and tenofovir (TDF); however, among patients treated with ETV, HBsAg was significantly more often eliminated in HBeAg (+) patients. Conclusions: The HBsAg elimination in patients undergoing antiviral treatment occurs more often in men, patients with positive HBeAg before treatment, individuals above 60 years, and patients treated with ETV.

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)

Biomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core-related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy. Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss. CHB patients who completed therapy with 48weeks peginterferon alpha2b±nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg-negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR). HBsAg loss occurred in 15/114(13%) HBeAg-negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound. On-treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72weeks was week 8 qHBsAg <70IU/mL.

Impact of hepatitis B virus-related immune reconstitution inflammatory syndrome on HBsAg loss in patients co-infected with human immunodeficiency virus

Impact of hepatitis B virus-related immune reconstitution inflammatory syndrome on HBsAg loss in patients co-infected with human immunodeficiency virus

Peripheral soluble protein, transcriptomic, and methylation biomarkers associated with HBsAg loss in patients with chronic hepatitis B

Peripheral soluble protein, transcriptomic, and methylation biomarkers associated with HBsAg loss in patients with chronic hepatitis B

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients

Background and aimRecently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. MethodsThe ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. ResultsALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. ConclusionsALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

2305 HBSAg Seroclearance and Seroconversion Among Male Filipino Americans With Chronic Hepatitis B

INTRODUCTION: Worldwide prevalence of HBV infection, defined as presence of HBSAg is estimated at 257 million, and a 2009 study on HBV prevalence in the United States is estimated to be 2.2 million individuals. The chronic effects of HBV infection include cirrhosis and liver cancer and the disease burden impacts health care resources. Therefore, in 2009, the Centers for Disease Control has recommended HBV screening for patients who were born in geographic areas that has high HBV prevalence. The Philippines has approximately 8-12% HBV infection, and Filipino Americans account for a significant number of individuals migrating to the USA. HBSAg seroclearance (loss of HBSAg) and seroconversion (development of HBSAb) is described to be rare, and to our knowledge, has not been documented among patients who reside in the United States. In this case series, we describe our experience of 5 patients with this rare event. CASE DESCRIPTION/METHODS: Electronic medical records from our clinic Las Vegas Gastroenterology (Clark County, Las Vegas, NV) were retrospectively reviewed with ICD 9 and 10 codes (070.30, 070.32, B16.9, B19.10, B19.11). Of these we describe 5 HBSAg positive, HBeAg negative, HBeAb positive patients: 2 patients received treatment and 3 patients were treatment naive. All of these patients were of Asian descent (Filipino American), all males, with ages 45-55 years when initially seen in clinic. The 2 patients who received treatment, both had seroclearance while only 1 had seroconversion. Both patients were treated with TDF, with average treatment duration of 8 years prior to seroclearance. The 3 patients who were treatment naive all did not meet treatment criteria on presentation, and were followed for average duration of 6 years (3-8 years). All patients had spontaneous seroclearance and seroconversion. DISCUSSION: Our study describes HBSAg loss in patients with chronic HBV infection, which is relatively sparsely documented among chronic HBV patients in the United States. Interestingly, these patients were all males, all Filipino Americans and majority of the patients described in this case series were treatment naive. Further studies on the effect of gender, race and ethnicity are essentially in understanding the natural history of chronic HBV infection.

Baseline HBsAg levels associated with HBsAg loss in HBeAg-negative chronic hepatitis B infection with persistently normal alanine aminotransferase

We aimed to assess the long-term outcomes of e antigen-negative chronic hepatitis B (CHB) infection with low hepatitis B virus (HBV) DNA level (< 200 IU/mL) and persistently normal alanine aminotransferase (PNALT) and to explore the factors associated with the results. This retrospective cohort study enrolled consecutive baseline CHB patients with PNALT from January 2005 to June 2008. In total, 252 e antigen-negative CHB patients with PNALT and low HBV DNA level (< 200 IU/mL) were enrolled, of whom 188 were eligible for this analysis. Among the 188 patients, 131 were followed up more than twice per year and 57 were followed up at least once per year, with a median follow-up period of 102 (73-123) months. Of 188 patients, 16 had HBV DNA level of > 200 IU/mL and PNALT, 164 had HBV DNA level of < 200 IU/mL and PNALT and 8 had HBV DNA level of > 200 IU/mL and elevated ALT level, of which 3 used an antiviral drug during follow-up. Twelve of 164 experienced HBsAg loss. Cox regression analysis suggested that baseline HBsAg levels were associated with HBsAg loss in patients after follow-up, especially the baseline HBsAg levels of < 200 IU⁄mL, which is a risk factor for HBsAg loss. The AUC of baseline HbsAg level in the e antigen-negative CHB group was 0.772 (cutoff value 426, P < 0.001). The cumulative probability of HBsAg loss in the HBsAg < 400 IU/L group was 20% (7/35), which ws higher than that in the HBsAg ≥ 400 IU/L group (3.88%; 5/129; X2 = 11.75, P = 0.0006). The e antigen-negative CHB infection with low HBV DNA level (< 200 IU/mL) and PNALT will progress to chronic hepatitis, although the probability of its occurrence is low. Spontaneous HBsAg loss may not occur frequently because the manifested cumulative probability of HBsAg loss was higher in the HBsAg < 400 IU/L group than in the HBsAg ≥ 400 IU/L group.

Hepatitis B Surface Antigen Loss with Tenofovir Disoproxil Fumarate Plus Peginterferon Alfa-2a: Week 120 Analysis

Background and AimsHepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120.MethodsIn an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed.ResultsRates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P < 0.001 for both) or group D (HBsAg loss: P = 0.002; HBsAg seroconversion: P < 0.001).ConclusionsThe results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.

Activity of nucleic acid polymers in rodent models of HBV infection

Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs).The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36–79% relative to baseline) reductions in WHsAg (4/10 animals) after 3–5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment.In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections.

The Predictive Value of Baseline HBsAg Level and Early Response for HBsAg Loss in Patients with HBeAg-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment

ObjectiveTo explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. MethodsA total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment. ResultsThe median treatment time for HBsAg loss was 84 weeks (7–273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). ConclusionBaseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

L-Carnitine Deficiency Causing Hypoxic Respiratory Failure Due to Recurrent Flash Pulmonary Edema

SESSION TITLE: Student/Resident Case Report Poster - Pulmonary Manifestations of Systemic Disease I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: We present a unique case of recurrent flash pumonary edema associated with L-carnitine deficiency. The purpose of our case is to establish clinical significance of L-carnitine replacement, since its deficiency causes pulmonary edema, especially in chronic hepatitis patients. CASE PRESENTATION: 45-y/o African American female with history of cirrhosis from chronic Hepatitis B on Lamivudine was admitted with one week of productive cough with pleuritic pain, nausea and lethargy. On physical exam there were decreased breath sounds bilaterally. ProBNP was elevated at 5297 ng/L. Chest X-ray (pic 1) and CT chest (pic 2) showed bilateral pulmonary vascular congestion without pleural effusions. 2D Transthoracic ECHO showed LVEF-60% with diastolic dysfunction. Upon admission, patient was intubated for acute hypoxic respiratory failure secondary to pulmonary edema. HIV-PCR, PCP, Urine for Legionella Antigen, and AFB cultures were negative. Patient was started on antibiotics for pneumonia based on BAL cultures that grew ESBL E.coli. Patient's severe sepsis significantly improved, but failed multiple weaning trials. She developed recurrent flash pulmonary edema, as noticed on CXR, at the time of weaning from mechanical ventilation that prompted us to check serum carnitine level. Her carnitine levels were extremely low. Despite multiple aggressive attempts to diurese the patient, her clinical condition continued to deteriorate, due to recurrent flash pulmonary edema, requiring hemodialysis until carnitine was replaced. Following carnitine replacement patient’s clinical condition significantly improved, recurrent pulmonary edema completely resolved and hemodialysis was discontinued. DISCUSSION: Serum carnitine is readily measurable and can easily be substituted, but there are no guidelines yet for adults (1). Carnitine levels in patients with chronic hepatitis are lower than in healthy individuals. There are case reports that suggest secondary carnitine deficiency due to some medications like Valproate, Adefovir and Zidovudine. In our patient, carnitine deficiency could be due to chronic hepatitis or even Lamivudine (2,3). CONCLUSIONS: We can clearly establish from our case that carnitine deficiency must be considered as a reversible cause for recurrent flash pulmonary edema in chronic hepatitis patients. Prompt recognition and replacement of carnitine reverses the clinical symptoms. Reference #1: E. Gilbert. Carnitine deficiency. Pathology, 1985;17(2):161-71. Reference #2: M. Vilaseca, R. Artuch, C. Sierra, et al. Low serum carnitine in HIV-infected children on antiretroviral treatment. European Journal of Clinical Nutrition, 2003;57:1317-1322. Reference #3: L. Jansen, A. Niet, F. Stelma, et al. HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels. Journal of Hepatology, 2014;61(4):730-737. DISCLOSURE: The following authors have nothing to disclose: Alexandra Sokolova, Shruti Patel, Jagadish Akella No Product/Research Disclosure Information

P0649 : Characterization of HBsAg loss in patients with chronic hepatitis B (CHB) treated with nucleos/tide analogs (NUCs): A retrospective multicenter study (HEBESAS)

P0649 : Characterization of HBsAg loss in patients with chronic hepatitis B (CHB) treated with nucleos/tide analogs (NUCs): A retrospective multicenter study (HEBESAS)

HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels

Achievement of HBsAg loss remains the hallmark of chronic hepatitis B treatment. In order to identify host factors contributing to treatment-induced HBsAg loss, we performed a genome-wide screen of single nucleotide polymorphisms (SNPs) and studied its immunological consequence. Chronic hepatitis B patients (40 HBeAg-positive and 44 HBeAg-negative) treated with peginterferon alfa-2a and adefovir were genotyped for 999,091 SNPs, which were associated with HBsAg loss at week 96 (n = 9). Plasma carnitine levels were measured by tandem-mass spectrometry, and the effect of carnitine on the proliferative capacity of hepatitis B virus (HBV)-specific and non-specific CD8 T cells was studied in vitro. One polymorphism, rs12356193 located in the SLC16A9 gene, was genome-wide significantly associated with HBsAg loss at week 96 (p = 1.84 × 10(-8)). The previously reported association of rs12356193 with lower carnitine levels was confirmed in our cohort, and baseline carnitine levels were lower in patients with HBsAg loss compared to patients with HBsAg persistence (p = 0.02). Furthermore, we demonstrated that carnitine suppressed HBV-specific CD8 T cell proliferation. In chronic hepatitis B patients treated with peginterferon and adefovir, we identified strong associations of SLC16A9 gene variation and carnitine levels with HBsAg loss. Our results further suggest that a lower baseline plasma carnitine level increases the proliferative capacity of CD8 T cells, making patients more susceptible to the immunological effect of this treatment. These novel findings may provide new insight into factors involved in treatment-induced HBsAg loss, and play a role in the prediction of treatment outcome.

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.

Dynamic changes and clinical significance of HBcAg18-27 specific cytotoxic T lymphocytes in acute hepatitis B patients

This report aims to investigate the dynamical changes of HBcAg18-27 epitope specific cytotoxic T lymphocytes(CTL), alanine aminotransferase (ALT), HBV DNA and HBsAg in peripheral blood of acute hepatitis B patients, and to explore the roles of HBcAg18-27-specific CTLs in virus clearance and liver injury. Acute hepatitis B (AHB) and chronic hepatitis B (CHB) patients were divided into two groups according to results of HLA-A0201. Patients with positive HLA-A0201 were classified into HBcAg-specific CTL group and those with negative HLA-A0201 were referred as control group. The specific CTLs were stained with HLA-A0201 limited HBcAg18-27 epitope MHC-Pentamer and the frequencies of CTLs, T, B, NK and NKT cells were detected by flow cytometry (FCM). The serum ALT, HBV DNA and HBsAg were examined using speed analysis, quantitative PCR and abbott chemiluminescent technology. The frequencies of HBcAg18-27-specific CTLs in AHB patients were higher in the early three weeks as compared to the late three weeks. The apex time of HBV-specific CTL frequencies lagged behind those of HBV DNA, HBsAg and ALT. The loss of HBsAg in patients with high frequencies of HBV-specific CTL was earlier than that in patients with low frequencies (t = 2.018, P value is less than 0.05). In the second week the peak frequencies of CD3+CD8+ cells overlapped with that of HBcAg18-27-specific CTLs and with a positive correlation between (r = 0.420, P value is less than 0.05). During the early stages of AHB, the frequencies of NK and NKT cells were found significantly lower than that of control group and CHB group and the levels were back to normal after recovery. Moreover, a negative correlation existed between the frequencies of NK cells and the dynamic changes of HBcAg18-27-specific CTLs (r = -0.435, P value is less than 0.01) in AHB group. The frequencies of HBcAg18-27-specific CTLs were significantly higher as compared to CHB group in the first three weeks (z = -3.258, -4.04, and -3.259, P value is less than 0.01). The early loss of HBsAg was closely related to the high frequencies of HBcAg18-27 specific CTLs in AHB patients. HBcAg-specific CTL frequencies in peripheral blood could be used to predict clinical outcome after HBV infection. The frequencies of CD8+ T cells can reflect the changes of frequencies of HBcAg-specific CTL during acute HBV infection.

New globally faces of hepatitis B and C in the world.

Worldwide, infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) have become a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) and the major global problems for public health in the world and Iran (1–3). HBV infection is the main cause of chronic liver disease in Iran (4) and the seroprevalence of HBV infection in Iran has been decreased during the last two decades (5). The main risk factor for HBV transmission was related to maternal-to-infantile transmission and the infantile vaccination with high coverage is the main cause for changes in epidemiology of HBV infection. But today, we have more risk factors for transmission in adulthood. The community contacts more in adolescence and the health policy makers should attend more for control of HBV infection. People awareness, risk factors modifications, harm reduction programmes in young addicted persons, vaccination against HBV in adults should be consider for control of HBV infection in future. We have less new cases, but we will have more cirrhotic cases and we need to consider the best therapy for prevention of HBV infection to end-stage phases. Therapy of HBV infection in which phase and which drugs are the debate. The goal of therapy in chronic hepatitis B (CHB) patients is sustained suppression of HBV viremia and decrease progression of liver disease to cirrhosis and HCC with the ultimate goal of improving survival. This can be pursued by maintaining constant inhibition of viral replication through a long term treatment with nucleos(t)ide analogs or by inducing, through the combined antiviral and immunomodulatory effects of interferon, a sustained immune response (6). Standard interferon is the oldest approved drug in therapy of HBV infection, but it has a limited response rate. Recently new published data have shown the better response with pegylated interferon in therapy of chronic HBV infection (7, 8). PEG-IFNα-2a has been licensed for the treatment of both HBeAg-positive and HBeAg-negative chronic HBV as a 48-week course, given by subcutaneous injection once weekly in a dosage of 180 mg. The main side effects of therapy with nucleos(t)ide analogs such as lamivudine, adefovir and entecavir, is emergence of resistance (9, 10). These events will decrease benefit of therapy with anti-viral agents. HBs Ag level in prediction of therapy response The main question was and is regarding how and when we can conclude the therapy in HBV infection is effective and we should continue or it is ineffective and we should discontinue it. During recent years serum HBsAg is hypothesized to be a marker for immunological response to therapy, independent of virological response as measured using HBV DNA levels, because of its correlation with intrahepatic HBV covalently closed circular (ccc) DNA, the main replicative template of HBV (11). HBsAg levels appear to differentiate patients in the inactive carrier state from those with active disease or from inactive carriers with a high probability of subsequent relapse. Furthermore, recent studies have shown that on- treatment HBsAg levels are predictive of a durable off-treatment response to peginterferon (PEG-IFN), and can accurately identify non-responders early during therapy, both in HBeAg-positive, and HBeAg-negative patients. Among those who underwent HBsAg loss within 6 years of follow-up, serum HBsAg levels were a better predictor than HBV DNA levels. Low serum levels of HBsAg, alone or in combination with HBV DNA levels, 1 year after HBeAg seroconversion can predict HBsAg loss in patients with HBV infection (12). Currently, multiple diagnostic assays are available for quantification of HBsAg. That we should use the validate method for diagnosis.

Serum and liver hepatitis B virus DNA after loss of HBsAg in patients with chronic hepatitis B

Serum and liver hepatitis B virus DNA after loss of HBsAg in patients with chronic hepatitis B