Glycyrrhizin withdrawal followed by human lymphoblastoid interferon in the treatment of chronic hepatitis B.

Seventeen patients with chronic hepatitis B were treated with a 4-week administration of glycyrrhizin followed by a 4-week treatment with human lymphoblastoid interferon, then followed for 6 months after the end of treatment. All were positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B virus-associated DNA polymerase (DNA-p) for at least 6 months before entry. All patients were Japanese and none of them were homosexuals. Eleven patients lost DNA-p activity and 10 of them lost HBeAg. Three of these 10 patients had antibody to HBeAg. In 10 patients who became HBeAg-negative, alanine aminotransferase levels after glycyrrhizin administration were higher and initial DNA-p activities relatively lower than the levels found in seven patients who remained HBeAg-positive. The immunomodulator provided by a short course of glycyrrhizin before administration of human lymphoblastoid interferon may be an effective treatment for patients with chronic hepatitis B.     

Changes of Intrahepatic Localization of Hepatitis B Core Antigen in HBeAg Positive Patients with Chronic Active Hepatitis B Treated with Interferon

The intrahepatic distribution of hepatitis B core antigen (HBcAg) was studied in 14 HBeAg-positive patients with chronic active hepatitis B who were treated with interferon. Patients received 5 to 6 million units daily of human lymphoblastoid interferon or human diploid fibroblast interferon for 28 days. Intrahepatic HBcAg was detected by the indirect immunoperoxidase technique. Before interferon therapy, the intrahepatic HBcAg was detected almost equally in both the nucleus and cytoplasm. The expression of nuclear HBcAg decreased significantly (p less than 0.001) after interferon therapy, irrespective of the outcome for DNA polymerase and/or HBeAg/anti-HBe status. The expression of cytoplasmic HBcAg decreased significantly (p less than 0.05) only in the patients who lost DNA polymerase after treatment, whereas it increased in patients with DNA polymerase and/or HBeAg in the serum. These findings suggested that a shift of intrahepatic HBcAg from the nucleus to the cytoplasm occurred in HBeAg-positive patients with chronic active hepatitis B receiving interferon therapy.     

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B

Background/Aims: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B.Methods: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis.Results: Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p=0.02 and 4.75; p=0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p=0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment.Conclusions: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.     

Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial

STUDY OBJECTIVE: To determine the efficacy of a short course of prednisone followed by recombinant interferon treatment in patients with chronic type B hepatitis. DESIGN: Randomized, controlled trial with a 5-month treatment phase and a 9-month observation period after treatment. SETTING: Two referral-based university-affiliated medical centers. PATIENTS: Thirty-nine clinically stable patients with chronic type B hepatitis, all of whom were positive for hepatitis B antigen, hepatitis B virus-associated-DNA (HBV-DNA), and DNA polymerase for at least 6 months before entry. Patients included 20 heterosexuals and 19 male homosexuals. INTERVENTIONS: Eighteen patients were treated with a 6-week tapered regimen of prednisone, followed by 90 days treatment with recombinant interferon alpha-2b; 21 patients were untreated controls. Paired liver biopsy specimens of 27 patients (pretreatment and 9 months after treatment) were blindly evaluated. MEASUREMENTS AND MAIN RESULTS: Nine treated patients had a sustained loss of HBV-DNA. In addition, eight treated patients lost hepatitis B e antigen and four became negative for hepatitis B surface antigen (HBsAg). When compared with controls the differences were statistically significant for clearance of HBV-DNA and HBsAg (P = 0.035 and 0.037, respectively). Treated patients who had a sustained loss of HBV-DNA had higher initial alanine aminotransferase lower initial DNA and DNA polymerase levels, and were more frequently heterosexual. Patients who responded to treatment with the disappearance of hepatitis B e antigen and HBV-DNA had normal liver function tests and markedly improved liver histology during follow-up. CONCLUSIONS: The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.     

A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy

Sixty-four heterosexual Italian carriers of HBsAg with chronic HBeAg and hepatitis B virus DNA-positive hepatitis were assigned randomly either to receive human lymphoblastoid interferon (injections of 5 million units per m2 three times per week for 6 months) or to serve as untreated controls. After 18 months of follow-up evaluation, 26 of the 33 treated patients (79%) had cleared hepatitis B virus DNA, 23 (70%) had lost HBeAg and 20 (61%) had seroconverted to anti-HBe. Fifteen of the 31 controls (48%) had cleared hepatitis B virus DNA (p = 0.01), 12 (39%) had lost HBeAg and nine (29%) had seroconverted to anti-HBe (p = 0.002). Eight treated patients but only one control had lost HBsAg and seroconverted to anti-HBs (24% vs. 3%, p = 0.01). Treated patients cleared hepatitis B virus markers after a mean interval of 4 months, compared with 8 months in the controls. All responders to interferon cleared intrahepatic HBcAg, and 50% showed histological improvement. The baseline hepatitis B virus DNA levels and the original histology were not predictive of a response to therapy; women appeared to respond better than men. Lymphoblastoid interferon provides an effective therapy in the heterosexual Italian patient with chronic hepatitis B.     

The effect of recombinant alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins in man

The effect of alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins was analyzed in eight patients with chronic type B hepatitis who participated in a pilot study of interferon therapy. Three individuals became HBsAg-negative, 4 lost HBeAg but remained HBsAg-positive and 1 remained positive for both HBsAg and HBeAg. Initiation of interferon treatment was rapidly followed by reduction or loss of hepatitis B virus DNA in the serum but by little immediate change in hepatitis B virus antigen levels. Changes in hepatitis B virus antigens were usually delayed. Loss of HBsAg from the serum was preceded by the sequential disappearance of pre-S-encoded proteins (pre-S1 and polymerized human serum albumin) and HBeAg. In patients who lost HBeAg but remained HBsAg-positive, serum levels of pre-S1 and polymerized human serum albumin usually, but did not always, decrease. The individual who remained HBsAg- and HBeAg-positive had unchanged serum levels of pre-S1, polymerized human serum albumin and HBsAg. These results suggest that alpha-interferon inhibits hepatitis B virus DNA replication but has little direct effect on synthesis of hepatitis B virus gene products.     

Long term effect of alpha interferon in children with chronic hepatitis B

BACKGROUND/AIMS: The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha. PATIENTS: A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months). RESULTS: Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients. CONCLUSIONS: After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not differ from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient.     

A randomized study of the effects of adenine arabinoside 5'-monophosphate (short or long courses) and lymphoblastoid interferon on hepatitis B virus replication

A previous randomized controlled study has shown a 30% rate of HBe antigen/antibody seroconversion within 1 year of a month course of adenine arabinoside-5'-monophosphate; no seroconversion occurred in the control group. In this study of patients derived from the same population, 45 hepatitis B virus carriers with chronic liver disease were randomized to receive either a short (4-week) course of adenine arabinoside-5'-monophosphate, a long (7 to 8-week) course of adenine arabinoside-5'-monophosphate or a 12-week course of lymphoblastoid interferon. Long-lasting suppression of hepatitis B virus replication with disappearance of serum hepatitis B virus DNA and clearance of HBeAg occurred within 12 months of treatment in four patients who received the short course of adenine arabinoside-5'-monophosphate and in five who received interferon. Of the nine responders, four also lost HBsAg. A response to antiviral therapy was accompanied by clinical and biochemical evidence of improvement in liver disease. None of the patients who received a long course of adenine arabinoside-5'-monophosphate responded. Peripheral neuropathy and myalgia were the most serious adverse effect affecting three recipients of the short course of adenine arabinoside-5'-monophosphate and eight recipients of the long course. Thrice weekly administration of interferon was well-tolerated. Further studies to identify the characteristics of the "responder patients" and large-scale controlled trials of antiviral therapy in these subgroups are indicated.     

Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.     

Interferon treatment in hepatitis B surface antigen-positive hepatitis B e antibody-positive chronic hepatitis B: role of hepatitis B core antibody IgM titre in patient selection and treatment monitoring

Chronic hepatitis B infection with the hepatitis B e antigen (HBeAg)-negative variant is associated with a severe clinical course and a low response rate to interferon (IFN). In an attempt to improve the chances of sustained response to interferon we designed a pilot study, using titres of IgM antibodies to hepatitis B core antigen (HBcAb IgM) to guide treatment initiation. Eighteen adults who were HBeAg-negative with biopsy-proven chronic active hepatitis (seven with cirrhosis) entered the study. They were followed-up bimonthly with routine liver function tests, and HBcAb IgM titres were also determined. Treatment (lymphoblastoid IFN 5 million units (MU) m^–2 three times weekly for 6 months) was started when the HBcAb IgM titre was increasing. Fifteen (83.3%) patients had normal alanine aminotransferase (ALT) levels and undetectable HBV DNA at the end of treatment. HBcAb IgM decreased in all responders. We observed a relapse in four patients (three with cirrhosis), in the first year after treatment, with an increase in ALT, HBV DNA and titre of HBcAb IgM. Eleven patients (61.1%) had a sustained response and eight of these 11 patients were followed-up for more than 18 months; two responders cleared hepatitis B surface antigen (HBsAg). Hence, the rate of sustained response to IFN in HBeAb-positive patients with chronic hepatitis is improved if treatment is started when HBcAb IgM levels are increasing.     

Prolonged (6 months) treatment of chronic hepatitis B virus infection with recombinant leukocyte A interferon

Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV-DNAp) and hepatitis B virus DNA (HBV-DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 X 10(6) IU/m2 or 10 X 10(6) IU/m2 body surface of recombinant interferon (rIFN)-alpha-2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV-DNAp became negative in 10 out of 12 patients (83%). After a 15-month follow-up, HBV-DNAp, HBV-DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non-responder patients became HBV-DNA and HBV-DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non-responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long-term rIFN-alpha-2A therapy has an antiviral effect in CAH due to HBV infection and is well tolerated.     

Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders

BACKGROUND/AIMS: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. METHODS: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. RESULTS: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P=0.002) or the combination regimen (32%, P=0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. CONCLUSIONS: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.     

The effects of antiviral agents on serum hepatitis B e antigen levels in chronic type B hepatitis

In the present study, aiming at the evaluation of the effects of antiviral therapy on hepatitis B e antigen (HBeAg) levels, serum HBeAg concentration was determined serially by a quantitative assay in 44 patients with chronic hepatitis B who received a total of 73 courses of antiviral treatment. The posttreatment HBeAg levels were significantly lower than pretreatment baseline in all treated groups, not only at the end of treatment but also 6 months after the completion of therapy. The proportional decrease in treated patients was significantly greater than in 15 untreated controls. Six months after the completion of treatment, serum HBeAg became negative in seven out of 25 treatments with interferon, seven out of 28 with adenine arabinoside, and five out of 20 with adenine arabinoside 5'-monophosphate. All patients who became negative for HBeAg had normalization of alanine aminotransferase as well. A progressive decrease in HBeAg in patients treated with multiple courses of drug was observed, and the frequency of negative tests increased, paralleling the number of courses of treatment. These results suggest that antiviral therapy may alleviate inflammatory changes in the liver by promoting clearance of HBeAg from the serum, and may eventually shorten the natural course of hepatitis associated with chronic hepatitis B virus infection.     

α-干扰素联合乙肝清热解毒颗粒治疗HBeAg阳性慢性乙型肝炎的多中心研究

目的观察α-干扰素联合乙肝清热解毒颗粒治疗HBeAg阳性CHB患者的临床疗效以及不良反应。方法选择符合干扰素应用指征并兼有湿热中阻证候的HBeAg阳性慢性乙型肝炎患者120例,分为三组,每组各40例,分别给予α-干扰素、α-干扰素联合乙肝清热解毒颗粒和乙肝清热解毒颗粒治疗,观察治疗前及治疗1、3、6个月后中医症候量化评分、不良反应和疗效。结果治疗24周后,联合组ALT复常率为52.5%,明显高于中药组的25.6%,而中药组症状改善优于干扰素组;联合用药组6个月时HBeAg转阴率较单用干扰素和乙肝清热解毒颗粒组明显增高,联合组HBVDNA转阴率和HBeAg/抗HBe转换率虽高于其他两组,但尚无显著性差异。结论α-干扰素联合乙肝清热解毒颗粒治疗HBeAg阳性慢性乙型肝炎可提高6个月时HBeAg转阴率,其安全性好,有必要扩大样本进一步验证。     

Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.     

Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis

Eighty-eight consecutive hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, heterosexual patients of Caucasian origin presenting with chronic hepatitis were followed for 1 to 15 years (mean, 5.4 years). During the study period, 45 (51%) patients cleared HBeAg and hepatitis B virus-deoxyribonucleic acid from serum and were followed for 53 +/- 29 months (mean +/- SD) after seroconversion to antibody to hepatitis B e antigen. All patients manifested biochemical improvement. During follow-up, 10 (22%) of the 45 patients experienced spontaneous reactivation of hepatitis B replication with reappearance of serum hepatitis B virus-deoxyribonucleic acid and, in 4 patients, of hepatitis B e antigen. All patients then showed biochemical exacerbation of disease. These serologic events were transient, lasting an average of 12 months, in 8 (80%) patients. All patients were asymptomatic or minimally symptomatic. Histologic findings of liver tissue from 7 patients showed progression from chronic active hepatitis to active cirrhosis in 2 (28%) patients, while in the remaining 6 cases histology remained unchanged or improved from chronic active to chronic persistent hepatitis. These data indicate that spontaneous reactivation of hepatitis B infection occurs in heterosexual patients with chronic hepatitis B and this event is usually transient and asymptomatic, although in some patients it may be the major cause of progressive hepatic damage.     

核苷(酸)类似物序贯干扰素治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎患者的临床观察

目的 观察HBeAg阳性慢性乙型肝炎(CHB)患者在核苷(酸)类似物抗病毒治疗基础上序贯聚乙二醇干扰素α-2a(PEG IFNα-2a)治疗48周血清HBsAg的变化.方法 6例HBeAg阳性CHB患者中,3例采用核苷(酸)类似物序贯PEG IFNα-2a治疗48周,3例维持原核苷(酸)类似物治疗方案,每12周采用实时PCR定量检测HBV DNA,采用时间分辨免疫荧光分析法检测HBsAg、抗-HBs、HBeAg、抗-HBe及抗-HBc.结果 核苷(酸)类似物序贯PEG lFNα-2a治疗48周后,3例序贯治疗患者血清HBsAg均消失,而维持原核苷(酸)类似物治疗患者血清HBsAg效价为100～320 IU/mL.结论 对核苷(酸)类似物治疗产生较好应答反应且伴有血清HBsAg效价明显下降的HBeAg阳性CHB患者,在核苷(酸)类似物抗病毒治疗基础上序贯PEG IFNα-2a治疗48周能有效促进血清HBsAg下降,并出现血清HBsAg消失的现象.     

Randomized controlled trial of adenine arabinoside 5'-monophosphate in chronic active hepatitis B: comparison of the efficacy in heterosexual and homosexual patients

Twenty-two heterosexuals and 21 homosexuals with chronic active hepatitis B and who had HBsAg, HBeAg and hepatitis B virus DNA in serum were randomized separately to receive adenine arabinoside monophosphate or placebo. In the 10 heterosexuals and nine homosexuals who received placebo, no change in hepatitis B virus DNA level and HBeAg was observed. Among the patients who received adenine arabinoside monophosphate, seven of the 12 heterosexuals and five of the 12 homosexuals lost hepatitis B virus DNA; five heterosexuals and three homosexuals also lost HBeAg; one homosexual lost HBsAg. There was no significant differences in response between heterosexual and homosexual patients. When results were pooled, there was a significant effect of adenine arabinoside monophosphate on hepatitis B virus replication. None of the 19 patients who received placebo but 50% of the 24 patients who received adenine arabinoside monophosphate were negative for serum hepatitis B virus DNA at 10 months after treatment (p less than 0.001) and none of the 19 patients who received placebo and 33% of the 24 patients who received adenine arabinoside monophosphate were negative for HBeAg in serum (p less than 0.005). Retrospective analysis showed that disappearance of hepatitis B virus DNA after administration of adenine arabinoside monophosphate was more common (i) in patients with a low pretreatment hepatitis B virus DNA level than in patients with a high pretreatment hepatitis B virus DNA level (8/11 vs. 4/13, p less than 0.05); (ii) in patients with a high pretreatment ALT level than in patients with a low pretreatment ALT level (10/14 vs. 2/10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of HBeAg/anti-HBe immune complexes in the reactivation of hepatitis B virus replication among anti-HBe chronic carriers

Sixty-four chronic hepatitis B surface antigen (HBsAg) carriers with hepatitis B e antibody (anti-HBe) were followed in order to detect reactivations of hepatitis B virus (HBV) infection and to assess the incidence and specificity of hepatitis B e antigen/hepatitis B e antibody (HBeAg/anti-HBe) immune complexes (ICs). In 18 out of 19 patients who suffered an increase in alanine transaminase (ALT) values, serum HBV-DNA reappeared co-occurring with the peak(s) of transaminases. HBeAg/Anti-HBe immune complexes were detected in 17/18 (94.4%) patients positive for HBV-DNA. In nine of them, the appearance of immune complexes co-occurred with prednisone therapy, in two following seroconversion after recombinant interferon alpha-2A treatment, and spontaneously in the remaining seven patients. When ALT levels dropped to normal values, immune complexes as well as HBV-DNA became undetectable. In conclusion, the detection of HBeAg/anti-HBe immune complexes seems to be a specific method to detect HBV replication among anti-HBe positive patients.