Clearance of HBsAg in patients with chronic hepatitis B treated by entecavir plus Peg IFNα-2b following initial entecavir monotherapy / 中华临床感染病杂志

Objective To analyze the efficacy of entecavir (ETV) combined with Peg IFNα-2b in chronic hepatitis B ( CHB) patients with low levels HBsAg following initial ETV treatment.Methods Sixty-nine CHB outpatients achieving serum HBsAg ＜2 000 IU/mL and HBV DNA＜100 IU/mL following initial ETV treatment in Pujiang People's Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to January 2016 were enrolled.Patients were randomly assigned in two groups: 39 patients in combination group received ETV (0.5 mg/d ) and Peg IFNα-2b (1.5 μg· kg－1· week －1, hypodermic injection), and 30 patients in ETV group received ETV (0.5 mg/d) alone.Serum HBsAg quantification, negative conversion rate of HBsAg and HBeAg , and levels of aminotransferase (ALT) were measured at baseline , 12th, 24th, 48th, 72th and 96th week after treatment.Results The levels of HBsAg in the combination group decreased gradually with the prolongation of therapy , which were lower than those in ETV group 24 week after treatment (Z＝－2.566,P＜0.05),and at 48th, 72th and 96th week (Z＝－3.499,－3.825 and －3.864,P＜0.01).Clearance of HBsAg appeared in the combination group at 24th week,the clearance rates were 7.70%(3/39) and 28.20%(11/39) at 24th and 96th week, respectively;while the clearance of HBsAg occurred in ETV group at 96th week, the clearance rate was only 3.30%(1/30).The negative conversion rates of HBsAg in combination group were higher than those in ETV group at 48th,72th and 96th week (P＜0.05 or＜0.01).In the combination group, there were 11 cases of clinical cure , 11 cases of clinical efficacy and 17 cases of clinical effectiveness , while there were 1, 1 and 28 cases in ETV group,respectively.The treatment effect of the combination group was better than that of ETV group(χ2＝18.496,P＜0.01).Serological conversion rates of HBeAg were 30.00%(6/20) and 65.00%(13/20) in combination group at 12th and 96th week, while those were 11.11%(2/18) and 22.22%(4/18) in ETV group at 48th and 96th week.There were significant differences in the HBeAg serological conversion rates at 12th, 24th, 72th and 96th week between two groups (P＜0.05 or ＜0.01). The levels of ALT in combination group increased at 12th and 24th week, which had significant difference compared with ETV group (Z＝－1.236 and －2.658,P＜0.05), and the ALT levels gradually declined 48 week after treatment in combination group and there were no statistical differences between two groups at other time points.The ETV combined with Peg IFNα-2b and low baseline HBeAg levels were associated with the clearance rate of HBsAg (both P＜0.01).Conclusions CHB patients with low HBsAg levels following initial ETV monotherapy can achieve high negative conversion rate of HBeAg and HBsAg with the combination treatment of ETV and Peg IFN α-2b.

Clinical analysis of modified Chaiping decoction in treating HBeAg-negative chronic hepatitis B / 中国中药杂志

To observe the clinical efficacy of modified Chaiping decoction for HBeAg-negative chronic hepatitis B under DaBianZheng theory(syndrome differentiation theory) guidance with understanding of purgative detoxing and modern pharmacology research of traditional Chinese medicine. The patients with HBeAg-negative chronic hepatitis B(n=119) were randomly divided into treatment group(n=69) and control group(n=50). The patients in treatment group were treated with the modified Chaiping decoction(6 doses per week, one dose every day in two times by oral administration), and the patients in control group were treated with lamivudine(LAM) (100 mg/time, once a day). All of patients were treated for 48 weeks. The liver functions, levels of DNA of hepatitis B virus (HBV-DNA) and clinical symptoms were observed at weeks 12, 24, 36 and 48 in both groups. The levels of ALT and HBV-DNA in serum were also observed 24 weeks and 48 weeks after treatment in two groups. There was no significant difference in total effective rate between treatment group and control group at week 24, but the total effective rate in treatment group was higher than that in the control group at weeks 12, 36 and 48(P<0.05); the improvement of liver functions in the treatment group was superior than that in the control group at weeks 12, 36 weeks and 48(P<0.01 or P<0.05), but there was no significant difference at week 24; the improvement of serum HBV-DNA in the treatment group was significantly lower than that in the control group at week 12(P<0.01), but there was no significant difference at weeks 24, 36 and 48; the negative converse rate of serum HBV-DNA in the treatment group was lower than that in the control group at weeks 12, 24 and 36(P<0.01 or P<0.05), but there was no significant difference at week 48; the improvement of fatigue, lassitude, abdominal distension and hypochondriac pain in treatment group was significantly better than that in the control group at weeks 12 and 24(P<0.01 or P<0.05), but there was no significant difference in the improvement of fatigue and hypochondriac pain at weeks 36 and 48; the abnormal rate of ALT in treatment group was significantly lower than that in the control group 24 weeks and 48 weeks after drug withdrawal(P<0.01); there was no significant difference in abnormal rate of serum HBV-DNA 24 weeks after drug withdrawal, but it was significantly lower than that in the control group 48 weeks after drug withdrawal(P<0.05). Modified Chaiping decoction with combination of long term medication and intermittent administration showed better clinical efficacy on HBeAg-negative chronic hepatitis B. Its prescription compositions shall be further optimized and consummated under guidance of disease differentiation and syndrome differentiation, and its clinical research on hepatic fibrosis and living quality shall be carried out.

Efficacy of entecavir or adefovir dipivoxil monotherapy in treatment of HBeAg-negative chronic hepatitis B patients with mildly elevated ALT / 中华全科医师杂志

Objective To evaluate the clinical efficacy of entecavir (ETV) or adefovir dipivoxil (ADV) monotherapy in treatment of HBeAg-negative chronic hepatitis B (CHB) patients with mildly elevated ALT.Methods One hundred and seven HBeAg-negative CHB patients with ALT elevated by 1-2-fold of upper limit of normal (ULN) were enrolled in this prospective study.Sixty patients were assigned to receive ETV monotherapy and 47 patients to receive ADV monotherapy for at least 96 weeks.The ALT and HBV DNA levels were measured every 3 months.The liver biopsy was performed in 35 patients prior to therapy.Drug resistance and adverse reactions were documented.Results Four cases in ETV group and 2 cases in ADV group were lost in follow-up.Among 35 patients with liver biopsy,30 (86％) cases had significant fibrosis (stage 2-4) or inflammation (grade 2-4).At weeks 96,serum ALT was normalized in 67％ (30/45) cases of ADV group,and 95％ (53/56) cases of ETV group (x2 =13.33,P ＜ 0.01) ; the proportion of patients with undetectable HBV DNA in ADV and ETV groups was 78％ (35/45) and 100％ (56/56) respectively (x2 =13.81,P ＜ 0.01).No drug resistance occurred in ETV group,while 2 patients in ADV group were found with virological breakthrough and were confirmed to be of variants associated with ADV resistance.No adverse reactions were observed in either group during the trial.Conclusion Present study suggests that most HBeAg-negative CHB patients with mildly elevated ALT have significant fibrosis or inflammation and entecavir monotherapy was more effective than adefovir dipivoxil monotherapy in treatment of the patients.

¿A quién tratar? / Who to treat?

Aunque el objetivo óptimo del tratamiento de la Hepatitis B, sería la erradicación del virus, con las terapias con que contamos, en la actualidad, esto se consigue en un porcentaje mínimo de los pacientes. Por lo tanto, según el conocimiento actual, queda claro que el tratamiento que genera y logra mantener una supresión de larga duración del HBV DNA en niveles indetectables, reduce la incidencia de enfermedad hepática avanzada y hepatocarcinoma y este debería ser el objetivo que se plantee al tratar a los pacientes. Para la decisión de qué pacientes tratar debe considerarse su perfil clínico, perfil serológico, bioquímico y valores de carga viral. En algunas ocasiones, el clínico completará el estudio con una biopsia hepática. Hay tres grupos de pacientes por considerar cuándo se evalúa el paciente para darle tratamiento y todos tienen criterios distintos que guiarán la decisión del médico tratante, a saber: pacientes con hepatitis crónica HbeAg positivo, pacientes con hepatitis crónica HbeAg negativo, pacientes con enfermedad hepática avanzada.

Even though the optimum objective of hepatitis B treatment would be the eradication of the virus, therapies available nowadays only get this result on a minimum percentage of patients. Therefore, according to current knowledge, it is clear that the treatment that generates and keeps a long term suppression of HBV DNA at undetectable levels, reduces incidence of advanced liver disease and hepatocarcinoma, and this should be the objective when treating patients. When deciding which patients to treat, it should be considered their clinical, serological, and biochemical profiles, as well as the values of viral burden. Sometimes, the physician will finish the research with a hepatic biopsy. There are three groups of patients to be considered when deciding who to treat and all of them have different criteria that will guide the decision of the physician. The three groups include patients with: Chronic hepatitis HbeAg positive, chronic hepatitis HbeAg negative, and Advanced Liver disease.

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia

The present study was conducted with 55 patients native from western Brazilian Amazonia, who were HBV-DNA positive after seroconversion of HBeAg. It is a descriptive case study, with the patients separated into two groups: with hepatitis and without hepatitis on histological examination. The aim of the present study was to describe the clinical and molecular characteristics of patients who are chronic carriers of HBsAg. The prevalence of hepatitis was 63.64 percent, with a predominance of males (41.82 percent) and a mean age of 42.5 years, occurring mostly in natives of the southeast sub-region (32.73 percent). Time was a variable proportional to the course of the disease and the most frequent symptoms were: dyspepsia, asthenia and loss of libido with the majority of the patients having history of prior contact with HBV or positive family history. Splenomegalia was the most frequent sign (40 percent). Among the tests, platelet count, serum albumin and prothrombin activity were significant in the diagnosis of hepatitis. Alpha-fetoprotein was greater in patients with hepatitis, and hepatocellular carcinoma was detected in 3.63 percent of the patients with hepatic cirrhosis. Three types of HBV genotypes were diagnosed: A, D and F in the samples amplified for gene S. Genotype A (AA) was observed in 54.54 percent of the cases with hepatitis, in contrast to other studies showing the predominance of genotype F in this region. We observed mutations in 36.36 percent, with a predominance of the mutations in the core promoter region (31.81 percent), due to the greater prevalence of genotype A in this study.

Efficacy of Lamivudine in Patients with Hepatitis B e Antigen-Negative Chronic Liver Diseases / 대한간학회지

BACKGROUND/AIMS: Lamivudine therapy is effective in inhibiting HBV replications in patients with HBeAg-negative chronic liver disease. However, the sustained response rate appears to be particularly poor, because the vast majority of patients relapse soon after cessation of therapy. The aim of this study was to evaluate the efficacy of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after response in patients with HBeAg-negative chronic liver disease. METHODS: Fifty-nine patients with HBeAg-negative chronic liver disease who have received lamivudine for at least 6 months, were studied. The mean duration of treatment was 14 months. Complete response was defined as undetectable serum HBV DNA by bDNA and normalization of ALT levels. Once HBV DNA disappearance and ALT normalization were observed, lamivudine therapy was continued for at least two additional months. The mean follow-up after cessation of treatment was 6 (1-22) months. RESULTS: Fifty-six patients were undetectable HBV DNA. The cumulative HBV DNA loss rates at 3 months and 5 months were 90% and 95%, respectively. The ALT normalization was observed in 52 patients. The cumulative ALT normalization rates at 6 months and 10 months were 78% and 86%, respectively. The complete response was observed in 52 patients. The cumulative rates of complete response at 10 months and 18 months were 80% and 88%, respectively. A predictive factor for complete response was only the duration of lamivudine treatment. Virological breakthrough was observed in 5 (8.5%). Thirty-four patients stopped taking lamivudine after 7.7 (2-15) months of the additional therapy. Seventeen of those patients (50%) experienced relapse. The cumulative relapse rates at 3 months, 6 months and 10 months were 24%, 47%, and 66%, respectively. The only predictive factor for relapse was the duration of additional lamivudine treatment after response. CONCLUSIONS: Lamivudine was an effective treatment of HBeAg negative chronic liver disease. Relapse, however, was usually observed after cessation of lamivudine. Our results showed that long-term lamivudine therapy is required in order to decrease the high relapse rates in patients with HBeAg-negative chronic liver disease.

Serum ALT and HBV DNA Levels in Patients with HBeAg-Negative Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: HBeAg-negative chronic hepatitis B (CHB) has a poor long-term prognosis. Since no precise clinically relevant HBV thresholds are known in HBeAg-negative CHB, the decision to treat is difficult. The aim of this study was to evaluate the levels of serum HBV DNA and transaminase and to investigate the correlation of these values in patients with HBeAg-negative CHB. METHODS: The study analyzed the sera from 82 patients with HBeAg-negative CHB, 61 men and 21 women. The mean age was 45 years. The patients were divided into two groups according to serum ALT levels: the patients with lower ALT level (n=52, UNL or= 2 X UNL). The level of serum HBV DNA was determined by the Cobas Amplicor HBV Monitor(TM) (Roche). RESULTS: The median serum HBV DNA level was 2.7 X 10(5) copies/mL in patients with HBeAg-negative CHB. The median serum HBV DNA level of patients with a higher ALT level (1.0 X 10(6) copies/mL) was significantly higher than that of patients with a lower ALT level (5.6 X 10(4) copies/mL)(p<0.001). The serum ALT level was correlated with serum HBV DNA levels in patients with HBeAg-negative CHB (r=0.416, p<0.001). The serum level of HBV DNA in patients with cirrhosis (median 2.0 X 10(5) copies/mL) did not differ from patients without cirrhosis (median 4.7 X 10(5) copies/mL). CONCLUSIONS: The level of serum HBV DNA was higher in patients with higher serum ALT level than it was in patients with lower serum ALT, and it was closely correlated with serum ALT levels in HBeAg-negative CHB.

Viral Breakthrough in HBeAg-Negative Chronic Hepatitis B Patients Receiving Lamivudine Therapy / 대한간학회지

BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. RESULTS: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.

Efficacy of Lamivudine in Patients with HBeAg-Negative and HBV DNA-Positive Chronic Liver Disease / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of lamivudine in patients with HBeAg-negative and HBV DNA-positive chronic liver disease. METHODS: Twenty-four chronic liver disease patients were enrolled whose serology had common characteristics of HBeAg (-), and anti-HBe (+) but HBV DNA (+). All had elevated alanine aminotransferase (ALT) levels. 150mg of lamivudine was given orally once daily for more than 6 months. The goal of this treatment was the elimination of HBV DNA in serum and normalization of ALT level. Once HBV DNA disappearance and ALT normalization were observed, lamivudine was continued for two additional months. HBeAg, anti-HBe, HBV DNA and ALT were followed up every 1-2 month during, and after, treatment. RESULTS: Median duration of treatment was seven months. HBV DNA became undetectable after a median one month of treatment and ALT activity was normalized in all 24 patients within six months. Among the sixteen patients who were followed for more than 12 months after cessation of treatment, six relapsed. The cumulative relapse rate at 12 months was 37.5%. CONCLUSION: Lamivudine suppresses HBV replication effectively and normalizes serum ALT in patients with HBeAg-negative and HBV DNA-positive chronic liver disease. The relapse rate after cessation of treatment seems to be relatively low.