Prevención de la transmisión maternoinfantil del virus de la hepatitis B. directrices sobre la profilaxis con antivirales en el embarazo / Prevention of mother-to-child transmission of hepatitis B virus. guidelines on antiviral prophylaxis in pregnancy

Según estimaciones de la Organización Mundial de la Salud (OMS), en el 2015 257 millones de personas en el mundo tenían la infección crónica por el virus de la hepatitis B (VHB) y 900 000 fallecieron a causa de ella, en la mayor parte de los casos de cirrosis o carcinoma hepatocelular. La mayoría de las defunciones asociadas con el VHB en personas adultas obedecen a infecciones contraídas al nacer o en los cinco primeros años de vida. En mayo del 2016, la Asamblea Mundial de la Salud aprobó la Estrategia mundial del sector de la salud contra las hepatitis víricas 2016-2021, en la que se hace un llamado a eliminar las hepatitis virales como amenaza de salud pública ­definida como una reducción de 90% de la incidencia de infecciones y una reducción de 65% de la mortalidad­ para el 2030. La eliminación de la infección por el VHB como amenaza de salud pública conlleva la necesidad de reducir la prevalencia del antígeno de superficie del virus de la hepatitis B (HBsAg) a menos de 0,1% en los niños de 5 años de edad. Esta meta se puede lograr mediante la vacunación de todos los recién nacidos contra la hepatitis B y otras intervenciones orientadas a prevenir la transmisión maternoinfantil del VHB

Characteristics of an outpatient chronic hepatitis B virus infection cohort / Caracterização de uma coorte ambulatorial de pacientes com infecção por vírus da hepatite B crônica

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. .

RESUMO Objetivo: Caracterizar uma coorte de pacientes com hepatite B crônica, segundo parâmetros iniciais e evolutivos. Métodos: Análise retrospectiva e descritiva dos dados clínicos e laboratoriais de portadores crônicos adultos do HBsAg, sem HIV, virgens de tratamento, com ao menos duas consultas ambulatoriais entre fevereiro de 2006 a novembro de 2012. Empregaram-se os testes exato de Fisher, χ², Wilcoxon, Spearman, Kappa e comparações múltiplas, o nível de significância estatística adotado foi de 5% e intervalo de confiança de 95%. Resultados: Foram incluídos 175 pacientes com média de idade de 42,95±12,53 anos, 93 (53,1%) do sexo masculino, 152 (86,9%) não reagentes para o antígeno e (HBeAg), 3 (1,7%) coinfectados com hepatite C, 15 (8,6%) cirróticos e 2 (1,1%) com carcinoma hepatocelular. Predominou o genótipo A. Constataram-se hepatite ativa em 66 pacientes (37,7%), imunotolerância em 6 (3,4%), estado de portador inativo em 38 (21,7%), exacerbações e/ou escapes virais em 16 (9,1%). Em 32 (18,3%), havia DNA viral persistentemente elevado e alanina aminotransferase normal; em 17 (9,7%), carga viral constantemente baixa e alanina aminotransferase alterada. Se fossem considerados apenas transaminases e DNA viral iniciais, 15 casos de hepatite ativa não teriam sido evidenciados. Fibrose avançada foi mais prevalente em HBeAg reagentes e associou-se direta e significativamente ao DNA do vírus da hepatite, idade e transaminases. Conclusão: Grande parte dos pacientes apresentou hepatite ativa. Porém, aproximadamente um quarto (todos pertencentes ao grupo HBeAg não reagente) foram identificados somente em função da análise conjunta das mensurações sequenciais de DNA do vírus da hepatite e transaminases, por vezes aliada a dados histológicos, após seguimento. .

Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients

BACKGROUND/AIMS: Relapse has been reported after stopping nucleos(t)ide (NUC) therapy in the majority of chronic HBeAg negative hepatitis patients. However, the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not well known. We investigated the frequency of relapse in HBeAg negative CHB patients receiving NUC therapy. METHODS: The NUC therapy was discontinued at least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients. Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal range. Virological relapse was defined as HBV DNA >2,000 IU/mL. RESULTS: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virological relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1 year sustained response. Of these factors, cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year virological relapse rate. Baseline HBV DNA and total treatment duration tended to be associated with virological relapse. CONCLUSIONS: Virological relapse developed in the majority (73.3%) of HBeAg negative CHB patients and clinical relapse developed in the half (53.3%) of patients at 1 year off therapy. Cirrhosis may be associated with the low rate of virological relapse.

Efficacy and predictors of the virologic response to entecavir therapy in nucleoside-naive patients with chronic hepatitis B / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to elucidate the antiviral efficacy and the predictors of entecavir treatment in nucleoside-naive chronic hepatitis B patients. METHODS: A total of 160 patients treated with entecavir (0.5 mg daily) for at least 24 weeks were consecutively enrolled. The virologic response (HBV DNA1 log10 copies/mL increase in HBV DNA level above nadir on two consecutive occasions) were retrospectively analyzed. RESULTS: The mean follow-up duration was 58.8 weeks, and 85 patients (53.1%) showed HBeAg positivity. The median pretreatment levels of serum ALT and HBV DNA were 99 IU/L and 7.6 log10 copies/mL, respectively. The cumulative rates at 12, 24, 48, and 72 weeks were 37.5%, 68.1%, 87.4%, and 95.8%, respectively, for the virologic response; 40.0%, 66.2%, 84.5%, and 92.7% for the biochemical response; 10.6%, 18.8%, 27.0%, and 34.5% for HBeAg loss; and 3.5%, 7.1%, 9.0%, and 13.2% for HBeAg seroconversion. There was no case of virologic breakthrough. An absence of HBeAg and a low serum HBV DNA level (<8 log10 copies/mL) at baseline were significant predictors of the virologic response in a multivariate analysis (P<0.01). CONCLUSIONS: Entecavir therapy showed excellent efficacy in nucleoside-naive chronic hepatitis B patients. The predictors of a virologic response were an absence of HBeAg and a low baseline HBV DNA level.

Predictors for virologic response in management of chronic hepatitis B / 대한간학회지

No abstract available.

Tea polyphenols exerts anti-hepatitis B virus effects in a stably HBV-transfected cell line / 华中科技大学学报（医学）（英德文版）

In this study, the anti-HBV effects of tea polyphenols (TP) were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2.15 cells were detected. TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the secretion of HBeAg in a dose-dependent (P<0.01) and time-dependent manner, with 50% maximal inhibitory concentration (IC50) value being 7.34 microg/mL on the 9th day, but the time-dependence was not significant (P=0.051). Expression of HBV-DNA in the supernatant of the cell culture also was significantly decreased in a dose-dependent fashion (P<0.01). The IC50 of TP in inhibiting HBV DNA was 2.54 microg/mL. It concluded that TP possessed potential anti-HBV effects and may be used as a treatment alternative for HBV infection.

Clinical efficacy of entecavir therapy and factors associated with treatment response in naive chronic hepatitis B patients / 대한간학회지

BACKGROUND/AIMS: Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to characterize the response to entecavir and to examine the factors affecting that response. METHODS: We administered 0.5 mg of entecavir once daily for more than 12 months to 114 naive chronic hepatitis B (CHB) patients. We measured the levels of liver enzymes, serological markers, and serum HBV DNA at 3-month interval. RESULTS: Normalization of serum alanine aminotransferase levels was observed in 68.5% (76/114), 74.6% (85/114), and 81.6% (62/76) of patients after 6, 12, and 24 months of therapy, respectively. HBV DNA levels of <50 copies/mL (as evaluated by polymerase chain reaction) were observed in 43.9% (50/114), 71.1% (81/114), and 85.5% (65/76) of patients after 6, 12, and 24 months, respectively. Viral breakthrough was not observed. The rates of HBeAg loss and seroconversion were 43.5% (27/62) and 14.5% (9/62), respectively, after 12 months of therapy, and 56.4% (22/39) and 15.4% (6/39) after 24 months. The independent factor associated with PCR negativity was early virologic response (EVR; HBV DNA <2,000 copies/mL after 3 months of therapy, P<0.001). The independent factors predicting HBeAg loss were found to be serum albumin levels (P=0.041) and EVR (P=0.005). CONCLUSIONS: Entecavir induced excellent biochemical and virologic responses in naive CHB patients. EVR was an independent factor for predicting HBV PCR negativity and HBeAg loss.

Risk factors for intrafamilial spread of hepatitis B in northeastern Bosnia and Herzegovina

Accurate estimations of hepatitis B virus transmission risk for any region in Bosnia and Herzegovina are not clearly established. We aimed to determine levels of risk associated with intrafamilial transmission of hepatitis B infection within families in our region. Family members of 81 chronic carriers of hepatitis B surface antigen [> 6 months positive and considered as index case] were tested for hepatitis B markers. For family members, we recorded their age, sex, and family relationship to the index case, and vaccination status. The proportion of HBsAg positive family members was 25/207 [12.1%], while the proportion of family members with evidence of exposure to HBV was 80/207 [38.6%]. Only 17/207 [8.2%] family members had eviddence of past HBV vaccination. Age was found to be a significant predictor of HBV exposure of family members [odds ratio 1.05, 95% CI 1.03-1.07, P < .001]. In a multivariate analysis, HBsAg positivity was associated with a female index case [odds ratio 11.31, 95% CI 3.73-34.32, P < .001], HBeAg positivity in the index case [odds ratio 5.56, 95% CI 1.80-17.23, P < .005] and being a mother of the index case [odds ratio 9.82, 95% CI 2.43-39.68, P < .005]. A female index case [odds ratio 4.87, 95% CI 2.21-10.72, P < .001], HBeAg positivity in the index case [odds ratio 3.22, 95% CI 1.15-9.00, P < .05] and being a mother of the index case [odds ratio 3.72, 95% CI 1.19-11.64, P < .05] were also risk factors for HBV exposure among family members. The combination of HBeAg positivity and female index case was a significant predictor for HBsAg positivity of family members [odds ratio 70.39, 95% CI 8.20-604.61, P < .001]. Children of HBeAg positive mothers are at highest risk for becoming chronic carriers themsselves and generally, the combination of female sex and HBeAg positivity dramatically increases the chances of HBV transmission within the family

HBeAg/anti-HBe, alanine aminotransferase and HBV DNA levels in HBsAg positive chronic carriers.

Serum samples from a total of 72 chronic hepatitis B virus carriers were analysed by serological, biochemical and molecular assays. The aim was to evaluate the relationship of the serological and biochemical parameters with molecular markers in order to assess the infectivity of virus. Out of 72 chronic HBsAg positive carriers, 28 patients were HBeAg positive and anti-HBe negative, 38 patients were HBeAg negative and anti-HBe positive, only 3 patients were positive for both HBeAg and anti-HBe and the rest 3 patients were negative for both markers. Detectable HBV DNA lcvcl was found in 92.86% HBsAg-positive/anti-HBe negative patients along with raised alanine aminotransferase (ALT) level (67.86%) compared with HBeAg-negative/anti-HBe positive carriers (36.84%) (p value = 0.02) and out a total of 38 HBeAg-negative/anti-HBe positive carriers, 12 (31.58%) patients had detectable lcvel of HBV DNA. Among the 14 HBeAg-negative/anti-HBe positive patients with elevated ALT level, 8 (57.14%) had detectable HBV DNA whereas out of 24 HBeAg-negative/anti-HBe positive patients with normal ALT level only 4 (16.66%) had detectablc HBV DNA lcvel. Significantly high rate of detection of HBV DNA was seen among anti-HBe positive patients with raised ALT level compared with the patients with normal ALT level (p value = 0.01).

Prevalence of Hepatitis B serological markers among health care workers in Baghdad, Iraq

Most previous studies on the prevalence of hepatitis B markers among Iraqi health care workers [HCW's] were limited to detection of HBsAg and anti-HBs antibodies. This work is a comprehensive one carried out to determine the prevalence of serological markers of HBV among a sample of Iraqi HCW's, and to elucidate the effect of various health professions, duration of professional practice, and the practice in different hospitals on exposure to HBV. A total of 1656 HCW's selected from various hospitals and medical units in Baghdad, together with 238 apparently healthy subjects [as control group] were screened for HBsAg and anti-HGs antibodies in the period from June 1995 to April 1998.All HBsAg positive subjects [HCWs and controls] were tested for anti-HBc [IgM], HBeAg and anti-HBe. Serum testing was carried out by enzyme-linked immunosorbent assay [ELISA]. A higher rate of HBsAg [5.4%] was observed among HCW's than controls [3.4%]. A significantly higher prevalence rate of anti-HBs antibodies in HCW's [39.3%] than controls [24.4%] was demonstrated. A significant difference in the prevalence of HBsAg was detected in the renal dialysis group only when each group was compared with the controls. The frequency of HBV infection was more than two times higher in HCW's with more than twenty years duration of professional practice compared to those with less than one year duration of practice. The lowest rate of HBsAg was seen among HCW's in general hospitals [4.8%], wherase the highest rate seen among those infectious diseases hospitals [9.0%]. HCW's still represent a high-risk group for HBV infection, and they may act as a potential source of infection to their contacts. Therefore vaccination of HCW's should be vigorously applied

Dynamics of HBV DNA levels, HBV mutations and biochemical parameters during antiviral therapy in a patient with HBeAg-negative chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection leads to long-term sequelae such as cirrhosis and hepatocellular carcinoma. Antiviral therapy aims at controlling the viral replication and thus, decreasing the likelihood of such complications. In this study, we evaluated the dynamics of biochemical and virological parameters over 10 years of antiviral therapy in a Thai patient with chronic HBeAg-negative HBV infection, who had relapsed after two courses of interferon alfa treatment. Lamivudine administration initially led to a significant reduction in alanine aminotransferase (ALT) and HBV DNA levels, but a subsequent emergence of YIDD mutants caused an ALT flare and a virus breakthrough. A 4-log HBV DNA decrease and normalization of the ALT level were achieved within 3 months of adefovir monotherapy without any relapse during follow-up exceeding 20 months. Thus, careful monitoring during treatment and knowledge of cross-resistance to antiviral salvage therapy are crucial for the management of patients with chronic hepatitis B.

Clinical Outcomes of Lamivudine Therapy in HBeAg Positive Chronic Hepatitis B with Minimally Elevated ALT / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to compare the efficacy of lamivudine therapy between chronic hepatitis B (CHB) patients, whose ALT levels less than 2 times the upper limit of normal (ULN) and patients whose ALT levels are more than 2 times ULN. METHODS: We retrospectively analyzed 508 consecutive patients with HBeAg-positive CHB who were treated with lamivudine for 1 year or more. Forty-six patients (Group A) with pretreatment ALT levels less than 2 times ULN were retrospectively compared with 462 patients (Group B) whose ALT levels are more than 2 times ULN. RESULTS: HBeAg seroconversion was achieved in 15 (32.6%) of group A and 162 (35.1%) of group B. The cumulative rates of HBeAg seroconversion in group A and B were 19% and 21% at 12 months; 35% and 31% at 24 months; and 38% and 39% at 36 months, respectively. HBV breakthrough was observed in 20 (43.5%) of group A and 192 (41.6%) of group B. The cumulative breakthrough rates of group A and B were 18% and 12% at 12 months; 33% and 29 % at 18 months; 45% and 42% at 24 months, respectively. Post-treatment relapse in group A and B occurred in 56% (5/9) and 41% (44/108), respectively. Therefore, the rates of the HBeAg seroconversion, breakthrough, and post-treatment relapse were not significantly different between these two groups. CONCLUSIONS: Lamivudine therapy in HBeAg-positive CHB patients whose ALT levels are minimally elevated is as effective as in treatment of the patients whose pretreated ALT levels are twice more than ULN.

Predictors of Lamivudine Resistance in Patients with Chronic Hepatitis B Virus Infection / 대한간학회지

BACKGROUND/AIM: Drug resistance is a major concern during nucleos(t)ide analogues therapy in patients with chronic hepatitis B virus (HBV) infections. The aim of this study was to measure the risk of lamivudine resistance provided for each predictive factor in patients with chronic HBV infections. METHODS: A total of 183 patients were analyzed among 315 patients with chronic HBV infections enrolled in a tertiary referral hospital between January 2001 and December 2003 on this retrospective cohort study. AST/ALT, HBeAg/anti-HBe, serum HBV DNA levels were tested for every 3 or 6 months. HBV DNA level was tested using Cobas Amplicor HBV Monitor test(TM). Viral breakthrough was defined as HBV DNA > or = 5 log10 copies/mL on two consecutive visits in patients who, on treatment, achieved HBV DNA < 5 log10 copies/mL. The risk of viral breakthrough was measured using Cox proportional hazards model for variables: age, sex, BMI (kg/m2), baseline ALT, HBeAg positivity, baseline HBV DNA level, serum HBV DNA level at 6 month of lamivudine therapy. RESULTS: The cumulative rates of viral breakthrough were 9.6%, 39.0%, 55.8% at 12, 24, 36 months, respectively. Serum HBV DNA level of 6 month of lamivudine therapy and presence of HBeAg were independent predictors for viral breakthrough. The relative risk was 1.43 (95% C.I. 1.09-1.89, P=0.010) for serum HBV DNA level at 6 months of lamivudine therapy and 1.77 (95% C.I. 1.06-2.95, P=0.029) for presence of HBeAg. CONCLUSIONS: Serum HBV DNA level at 6 months of therapy and HBeAg positivity were predictors of early lamivudine resistance in patients with chronic HBV infections. An alternate therapy should be considered when serum viral load is high at 6 months of lamivudine therapy.

The Efficacy and Safety of Telbivudine in Korean Patients with Chronic Hepatitis B / 대한간학회지

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

A comparative study on effect of lamivudine in wild and precore mutant variety of chronic hepatitis B virus infected patients.

The aim of this study is to evaluate the effectiveness of lamivudine treatment in both precore mutant and wild type of chronic hepatitis B (CHB) patients. The study was done on sixty CHB patients of both sexes seeking treatment in the Outpatient Department and admitted patients of Mymensingh Medical College Hospital. The patients were divided into two groups. Group A included chronic hepatitis B patients with raised ALT (> 80 u/l ) with HBeAg positivity, and group B included precore mutant variety of CHB patients with raised ALT (> 80 u/l) with HBeAg negativity. In Group-A, after 1 year of completion of lamivudine therapy there was 86.67% normalization of ALT, 23.33% HBeAg loss, 16.67% anti-HBeAg development and 73.33% HBV DNA loss. In Group-B, there was 76.67% normalization of ALT and 73.33% HBV DNA loss after 1 year of completion of therapy. In the present study, it was observed that lamivudine is equally effective in both wild and precore mutant variety of CHB patients. This was reflected by normalization of ALT and loss of HBV DNA. This study also shows the reappearance of HBV DNA during the later half of Lamivudine therapy which is due to YMDD mutation.

Role of HBV genotype in predicting response to lamivudine therapy in patients with chronic hepatitis B.

BACKGROUND: Predictors of response of chronic hepatitis B (CHB) to lamivudine therapy need better definition. Whether hepatitis B virus (HBV) genotypes could serve as such a predictor has not been well studied. AIM: To study the association of HBV genotypes with the outcome of lamivudine treatment in patients with CHB. METHODS: Seventy-six patients with CHB (45 HBeAg +ve) received lamivudine 100 mg/day, orally for 12 mo. Infecting HBV genotypes were determined in pre-treatment specimens using restriction fragment length polymorphism. End-of-treatment response (ETR) and sustained viral response (SVR) were defined as undetectable HBV DNA (< 0.5 pg/mL) at 12 and 18 months, respectively. RESULTS: ETR was observed in 26 (34%) and SVR in 11 (14%) patients receiving lamivudine. The pre-treatment characteristics of the responders and non-responders were comparable. Genotypes A and D were observed in 28 (37%) and 48 (63%) patients, respectively. The frequency of genotypes A and D was comparable between responders (28.6% vs. 37.5%) and non-responders (71.4% vs. 62.5%), respectively (p=ns). Of the 26 responders, SVR could be evaluated in 20 subjects; 9 (45%) relapsed and 11 achieved SVR. Patients with genotype D achieved higher SVR rate than genotype A (10 of 48, 28.8% vs. 1 of 28, 3.5% p =0.0359). CONCLUSIONS: Forty-five percent of Indian patients with CHB who achieve ETR relapse, and SVR to lamivudine therapy is achieved in 14%. Patients with genotype D achieve higher SVR rate than with genotype A.

Relationship between Serum HBV DNA Levels and Liver Histology in Chronic Hepatitis B / 대한소화기학회지

BACKGROUND/AIMS: Serum HBV DNA levels are correlated with hepatic histologic activity in chronic HBV infection based on HBeAg. Liver injury may persist, even though HBV DNA are not detected by hybridization assay. This study was to investigate whether serum HBV DNA levels determined by more sensitive quantitative method are correlated with histologic activities in chronic HBV infections. METHODS: This study included 66 chronic HBV infected patients. HBV DNA level was quantified by Cobas Amplicor HBV Monitor(TM). RESULTS: Serum HBV DNA levels in HBeAg-positive patients were significantly higher than HBeAg-negative patients. In HBeAg-positive patients, serum HBV DNA levels showed a significant negative correlation with portal-periportal activity and fibrosis (r=-0.451, -0.446 respectively). AST levels were correlated with lobular, portal-periportal activity and fibrosis (r=0.432, 0.365, 0.301 respectively), whereas ALT levels were related to lobular activity (r=0.294). Elevated AST levels predicted lobular activity, portal-periportal activity, and fibrosis with moderate to severe degree (OR 1.733, 95% CI 1.083-2.775; OR 1.518, 95% 1.028-2.243, p=0.336; OR 17.897, 95% CI 1.517-211.208, p=0.022, respectively). CONCLUSIONS: In HBeAg-positive patients, serum HBV DNA level correlates inversely with histologic activity. On the other hands AST level correlates with histologic activity and the stage of moderate or severe degree.

The Prevalence and Clinical Significance of Precore and Core Promoter Mutations in Korean Patients with hronic Hepatitis B Virus Infection / 대한간학회지

BACKGROUND/AIMS: Precore and core promoter mutations of hepatitis B virus (HBV) have been reported in Korea but their prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of precore and core promoter mutations and their relationships to hepatitis B e antigen (HBeAg) status, viral replication level, and severity of liver disease in Korea. METHODS: Among the patients who visited the Liver Diseases Clinics (Chung Ang University Hospital) between December 1998 and August 1999, 150 patients were randomly selected: 50 HBeAg-positive HBV-DNA positive patients by a branched DNA (bDNA) assay, 50 HBeAg-negative bDNA-positive patients, and 50 HBeAg-negative bDNA-negative patients. Serum HBV-DNA was amplified by a polymerase chain reaction (PCR) in these patients and the core promoter/precore HBV sequence was determined in 135 of the patients whose sera were positive for HBV-DNA by PCR. RESULTS: All of the 135 determined HBV-DNA sequences had HBV genotype with T at nucleotide 1858. Precore mutation (A1896) was detected in 95.7% of HBeAg-negative bDNA-positive patients and 94.9% of HBeAg-negative bDNA-negative patients. In HBeAg-positive patients 88% had wild type and 12% had mixture of wild type and A1896 mutant. Core promoter TA mutation (T1762/A1764) was detected in 93.5% of HBeAg-negative bDNA-positive patients, 94.9% of HBeAg-negative bDNA-negative patients and 74% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and liver disease severity or HBV-DNA levels. CONCLUSION: Precore stop codon mutation occurred almost invariably, along with HBeAg seroconversion, irrespective of subsequent viral replication levels or disease severity. Core promoter TA mutation was frequent both in the HBeAg-positive patients and HBeAg-negative patients irrespective of viral replication levels or disease severity.