免疫疗法联合干扰素治疗慢性乙型肝炎的初步研究

探讨免疫疗法联合干扰素治疗不同免疫应答期慢性HBV感染患者的疗效.145例慢性乙型肝炎患者(免疫耐受期66例,免疫清除期64例,残余整合期15例)随机分为联合治疗组(乙肝疫苗 胸腺肽 绿脓杆菌菌毛 干扰素,其中免疫耐受期42例,免疫清除期46例.共88例)和对照组(单用干扰素治疗,其中免疫耐受期24例,免疫清除期18例.共42例),观察ALT及病毒标志物变化.治疗后,免疫清除期联合治疗组的ALT复常率、HBeAg、HBV DNA阴转率和HBeAg/抗-HBe血清转换率均显著高于对照组(P＜0.05).免疫耐受期,治疗组HBeAg、HBV DNA阴转率和HBeAg/抗-HBe转换率均明显高于对照组(P＜0.05).免疫疗法联合干扰素治疗慢性乙型肝炎,疗效明显优于单用干扰素治疗.     

Occult hepatitis C virus infection among haemodialysis patients

Background and study aims

Hepatitis C virus (HCV) infection is a severe problem among patients on maintenance haemodialysis who are at particular risk for blood-borne infections because of prolonged vascular access and potential for exposure to contaminated equipment. Occult hepatitis C virus infection (OCI) is defined as the presence of HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable HCV antibody or HCV RNA in the serum. In this study, we aimed to investigate the existence of occult hepatitis C virus infection in PBMCs of haemodialysis (HD) patients in one center. Moreover, we tried to link the condition to risk factors associated with HCV infection in those patients.

Hepatitis C infection among Dutch haemophilia patients: a nationwide cross-sectional study of prevalence and antiviral treatment

Hepatitis C is a major co-morbidity among patients with haemophilia who received inadequately or non-virus-inactivated clotting factor concentrates before 1992. The objectives of this study were to investigate the prevalence of hepatitis C and the use of antiviral therapies during the last decade among patients with haemophilia in the Netherlands. We performed a cross-sectional study and a questionnaire was sent to all 1519 patients known with haemophilia in the Netherlands between 2001 and 2002. The study population for the present study consisted of 771 patients who had received clotting factor products before 1992 of whom 638 reported their hepatitis C status. In total, 441 of the 638 (68%) patients ever had a positive test for hepatitis C virus (HCV); 344 patients (54%) had a current infection, and 97 (15%) had cleared the virus. Among 344 patients currently HCV infected, 111 (32%) had received treatment for hepatitis C, while 34% (33/97) of patients with an infection in the past had been treated for hepatitis C. In 2002 the prevalence of hepatitis C among patients with haemophilia who received clotting factor products before 1992 was 54%. The majority of patients with a current HCV infection had not been treated with antiviral therapy.     

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.     

Infective endocarditis in heroin addicts: epidemiological observations and some unusual cases

The total number of cases of heroin-induced endocarditis occurring over a four-year period were reviewed in order to explain an increase in the number of cases in the last year studied (1975). Brown heroin was noted to be used more frequently by addicts during the period of increased incidence. Cultures of "street samples" of brown and white heroin as well as cocaine were obtained in order to elucidate a possible relationship between the increased use of brown heroin and the increased number of endocarditis cases. Despite frequent contamination of both white and brown heroin, none of the common endocarditis-causing pathogens were isolated from the samples. Staphylococcus aureus, the most common etiological agent, frequently resulted in tricuspid endocarditis. That the accepted criteria for tricuspid endocarditis may be present without actual cardiac valve involvement is demonstrated by a most unusual case of hepatic vasculature infection.     

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study

Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3′TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotheraphy appears disappointing, and other treatment strategies should be investigated.     

Case of mixed connective tissue disease associated with autoimmune hepatitis

Summary A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.