Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A non-B hepatitis.

OBJECTIVE--To determine the effect of low dose interferon alfa (human lymphoblastoid interferon) on aminotransferase activities in chronic non-A non-B hepatitis. DESIGN--Prospective randomised controlled parallel group study of active treatment versus no treatment carried out over 16 weeks and preceded by baseline measurements at weeks 8 and 4 and time zero. SETTING--HEPATOLOGY outpatient clinics in secondary referral centres. PATIENTS--Fourteen adults with histologically proved chronic hepatitis and persistently raised aminotransferase activities for six months or more. INTERVENTIONS--Seven patients randomised to receive interferon alfa 5 megaunits (MU) daily for one week, reducing to 5 MU thrice weekly for seven weeks, then 3 MU thrice weekly for eight weeks. Controls not treated. END POINT--Control of hepatic enzyme activity in chronic non-A non-B hepatitis. MEASUREMENTS AND MAIN RESULTS--Serum aspartate aminotransferase activity remained raised in controls (mean increase in study period 23.4 U/l) but fell rapidly to normal in the treated group (mean decrease 106.4 U/l). In four cases values were normal by eight weeks and in five cases by 16 weeks. Only minor side effects were recorded (fever, myalgia), which became less common as treatment progressed. CONCLUSIONS--Continuous low dose interferon alfa reduces aspartate aminotransferase activity to normal in most patients with chronic non-A non-B hepatitis and may prevent progression to cirrhosis.     

Efficacy of consensus interferon in treatment of HbeAg-positive chronic hepatitis B: a multicentre, randomized controlled trial

Hepatitis C virus (HCV) infection is an important public health problem worldwide. Its association with, and predisposing nature for diabetes mellitus (DM) has been long established. This research was carried out to determine the prevalence of Hepatitis C virus (HCV) amongst people with possible genetic predisposition to diabetes mellitus living in and around Vom, Plateau State, Nigeria. 188 subjects were screened after they filled a structured questionnaire to determine some of their demographic data, social habits and possible risk factors. 5 ml of blood was collected from each subject and sera separated out. Biotech's third generation ELISA Kit for HCV antibodies was used for the screening. Liver enzyme analysis was carried out on positive samples to determine their disease status. A prevalence of 14.36% was recorded with the highest seropositive group being those in the age bracket of 18 – 37 years. 13(13.40%) of males and 14(15.38%) of females were sero-positive. Liver enzyme analysis of sero-positive subjects showed increased levels which may imply early onset of liver damage. These result showed that these individuals could later suffer diabetes which may be triggered by their HCV infection if not treated. This is not over-looking the economic significance of their ill health, assuming they progress to cirrhotic HCV or develop hepatocelluar carcinoma due to HCV chronicity.     

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome.

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome. DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination. SETTING: Chronic fatigue clinic in a general hospital department of psychiatry. SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance. INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards. MAIN OUTCOME MEASURE: The self rated clinical global impression change score, "very much better" or "much better" being considered as clinically important. RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment. CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.     

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE--To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN--Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING--Four major medical centres in the United States. PATIENTS--12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES--In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS--Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS--Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.     

Acute and chronic infection of human lymphoblastoid cell lines with measles virus.

Several human continuous lymphoblastoid cell lines (LCL) having T or B characteristics were infected with low and high passage strains of measles virus. All of the cell lines were susceptible to one or the other or to both strains of measles virus with the production of typical syncytial giant cells and released cell-free infectious virus into the supernatant medium. There was no consistent pattern of susceptibility of LCL with either T or B characteristics to infection by measles virus. Viral induced cytolysis of the lymphoblastoid cells in many of the lines was marked, but in the LCL that could be maintained over longer periods of time, a state of chronic, less cytolytic and persistent infection could be established. The infection was characterized by the production of moderate amounts of cell-free infectious virus for up to 4 1/2 months after initial infection with little change in the number of viable cells in culture. Long-term low multiplicity of infection (MOI) experiments demonstrated that the cell-free infectious virus was being produced only by a small number of cells, but the majority of cells in culture contained measles antigen that was in a cell-restricted, noninfectious, or defective form. Electron microscopic examination of the chronically infected cells demonstrated that many of them contained aggregates of hollow tubular intranuclear nucleocapsids whose "stripped" appearance was in marked contrast to the larger granular intracytoplasmic nucleocapsids found during earlier stages of infection. It is theorized that the persistent infection of LCL may serve as a model in understanding the immune mechanisms which permit latent and chronic measles infection in man.     

Randomised controlled trial of nicotine chewing-gum.

The effectiveness of 2 mg nicotine chewing-gum as an aid to stopping smoking was compared with a placebo containing 1 mg nicotine, but unbuffered, in a double-blind randomised trial. Of 58 subjects given the active gum, 27 (47%) were not smoking at one-year follow-up compared with 12 (21%) of the 58 subjects treated with placebo (p less than 0.025). By the most stringent criterion of outcome, 18 (31%) subjects in the active treatment group and eight (14%) in the placebo group had not smoked at all from the start of treatment to follow-up at one year (p less than 0.05). Subjects receiving the active gum experienced less severe withdrawal symptoms and rated their gum as more helpful than did the placebo group. Minor side effects were common but only gastric symptoms were more frequent with the active gum. Subjects receiving active gum used it for longer than those receiving placebo but most stopped using it within six months and only four (7%) developed longer-term dependence. The number of gums used daily correlated significantly with pretreatment blood nicotine concentrations in the active treatment group and with pretreatment cigarette consumption in the placebo group. A lower pretreatment blood nicotine value was the best predictor of success at one year (p less than 0.001) but there was no significant relation to cigarette consumption, sex, and social class. The results clearly confirm the usefulness of nicotine chewing-gum as an aid to stopping smoking and imply a definite role for nicotine in cigarette dependence and withdrawal. Successful use of the gum requires careful attention to subjects'' expectations and clear instructions on how to use it.     

慢性乙型肝炎病毒感染自然史中HBsAg和HBsAb共存血清学模式分析

目的分析慢性乙肝病毒感染者HBsAg和HBsAb共存模式中血清学指标、HBV-DNA和肝酶等指标与自然病程的关系,探讨其临床意义。方法回顾性分析2016年重庆医科大学附属第一医院HBsAg和HBsAb双阳性患者的血清学指标、HBV-DNA和ALT、GGT检测结果,并对其感染的自然病程进行分析。结果 2016年该院HBsAg和HBsAb双阳性患者共520例,占全部HBV感染者的2.80%,占总送检标本数的0.42%。可分期的184例双阳性患者中,免疫耐受期47例(25.54%),免疫清除期17例(9.24%),低复制期108例(58.70%),再活动期12例(6.52%),HBsAg、HBsAg/HBsAb比值、HBV-DNA、ALT和GGT水平差异均有统计学意义(P<0.05),低复制期患者HBsAg/HBsAb比值均低于其他患者(P<0.05)。不同分期患者HBsAb、年龄和性别比较差异无统计学意义(P>0.05),且HBsAb水平均较低。284例资料完整HBsAg和HBsAb共存病例中HBV-DNA阳性136例,占47.89%。HBsAg浓度与HBV-DNA载量成正相关(r=0.295,P<0.05),HBsAb浓度与HBV-DNA载量之间没有显著相关性(r=0.04,P>0.05)。结论 HBsAg和HBsAb共存患者并不少见,与性别无关,可发生在各个年龄阶段,以低复制期患者为最多。HBsAg和HBsAb共存患者中HBsAb多以低浓度形式存在,且浓度与自然病程无关。HBsAb的出现并非代表患者体内病毒复制停止,在诊断及治疗HBsAg和HBsAb共存模式的乙肝病毒感染者时仍需结合HBV-DNA载量来判断感染状态。     

Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.

OBJECTIVE--To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN--Open randomised multicentre trial with three year follow up. SETTING--Outpatient departments of six French hospitals. PATIENTS--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS--Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.     

慢性乙型肝炎治疗的适应症和治疗方案的最新进展

目前,对于治疗一些慢性乙型肝炎病毒(HBV)感染边缘病例的最佳方法尚存在争议.血清HBV DNA和转氨酶水平、炎性坏死的程度和肝硬变程度决定着治疗的方案.所有转氨酶升高(＞正常上限值2倍)和血清HBVDNA＞20000 IU/mL的患者都需进行治疗.肝脏活检对于制定转氨酶轻度升高和血清HBV DNA＜20000 IU/mL的病例的治疗决策非常重要.慢性HBV患者如未接受治疗则需长期随访.现有7种药物获批用于治疗慢性乙型肝炎:普通和聚乙二醇IFNα、拉米夫定、阿德福韦、恩替卡韦、替比夫定和替诺福韦.应用聚乙二醇IFNα 1年疗程后持续治疗后效应使HbeAg阳性慢性乙型肝炎患者缓解率为30%-32%.口服抗病毒药物适用于大部分患者,并被用于长期治疗.然而,病毒耐药是长期口服抗病毒药物的主要缺点.     

Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.     

Prevalence of hepatitis B virus in chronic hepatitis B patients

The aim of the current study was to detect HBV by Real time - PCR in chronic hepatitis B patients. Fifty-eight sera of chronic hepatitis B patients were subjected during the period March 2009 to April 2010 in Ilam cities in West of Iran. Sera assayed by real-time PCR and ELISA methods. Twenty serum samples from healthy volunteers and non-hepatitis B patients and negative for hepatitis B seromarkers served as negative controls for the study. Among fifty-eight sera, ELISA showed fifty-five (94.8%) of the samples were positive for HBsAg and three (5.2%) negative results obtained while real-time PCR specified fifty-eight (100%) positive results in chronic hepatitis B patients. HBsAg status did not necessarily reflect HBV DNA level in the serum, as 5.2% of chronic Hepatitis B patients were positive for HBV DNA but negative for HBsAg. HBV DNA was not found to be positive amongst any of the negative controls. Real time - PCR is a sensitive and reproducible assay for HBV DNA quantization.     

Randomised controlled trial for evaluation of fitness programme for patients with chronic low back pain.

OBJECTIVE--To evaluate a progressive fitness programme for patients with chronic low back pain. DESIGN--Single blind randomised controlled trial. Assessments were carried out before and after treatment by an observer blinded to the study and included a battery of validated measures. All patients were followed up by postal questionnaire six months after treatment. SETTING--Physiotherapy department of orthopaedic hospital. SUBJECTS--81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy. The patients were randomly allocated to a fitness programme or control group. INTERVENTION--Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care. Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool. RESULTS--Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index (P < 0.005), pain reports (sensory P < 0.05 and affective P < 0.005), self efficacy reports (P < 0.05), and walking distance (P < 0.005). No significant differences between the groups were found by the general health questionnaire or questionnaire on pain locus of control. A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months. CONCLUSION--There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain. Further clinical trials, however, need to be established in other centres to confirm these findings.     

Immunology of hepatitis B virus and hepatitis C virus infection

More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and survival strategies. This review assesses recent advances in our understanding of viral hepatitis, contrasts mechanisms of virus-host interaction in acute hepatitis B and hepatitis C, and outlines areas for future studies.     

Dynamics of hepatitis B virus infection

Mathematical models of the dynamics of HIV and hepatitis C virus infection have proven to be of great utility in understanding pathogenesis and designing better treatments. Here, we review the state of the art in modeling and interpreting data obtained from hepatitis B virus infected patients treated with antiviral agents.     

Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE--Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS--For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS--Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.