A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients

Background : The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients.
Methods : Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis.
Results : After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P <0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P -value of 0.057.
Conclusions : The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.     

Low prevalences of HBV and HCV infection in patients with primary biliary cirrhosis in Taiwan: A case control study

To study the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC) against the background of HBV and HCV infection in the general population, serum specimens from a consecutive series of 27 patients with PBC and 108 age/sex matched ‘healthy subjects’ as control group were submitted to assays for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis B surface antigen (anti-HBs) and antibodies to hepatitis C virus (anti-HCV). None of the patients with PBC were HBsAg or anti-HCV positive while 17 (15.7%) and 6 (5.6%) of ‘healthy’ controls were HBsAg positive and anti-HCV positive (P= 0.017 and 0.26). Patients with PBC also had a significantly lower prevalence of HBV infection than matched controls (70.4%vs 88.9%, P= 0.022). The results suggest that neither HBV nor HCV plays any significant role in the pathogenesis of PBC, and that PBC would not develop or be masked in patients with HBV or HCV infection.     

Evidence of transmission of hepatitis B virus to spouses from sequence analysis of the viral genome

Heterosexual contact is one of the common routes of transmission for hepatitis B virus (HBV) among adults in Taiwan, but only a few studies have provided direct evidence at the level of the HBV genome of infected couples with acute non-fulminant hepatitis to document a common source. By cloning and sequencing polymerase chain reaction-amplified HBV-DNA, we analysed the sequences of the conserved region of the surface gene (nucleotide (nt) 305–513, representing 6.5% of the viral genome) of HBV in five HBV-infected index patients, their spouses and four randomly selected HBV carriers as controls. Risk factors associated with acute HBV infection in index cases were sexual contact with their spouses within 3 months before the onset of hepatitis. For all five couples, the HBV-infected index patient and the spouse shared a 100% sequence homology of HBV-DNA. In contrast, there was significantly more variation (mean heterogeneity 6.1%, range 1–13.9%) in the amplified region between the five couples and between each couple and the controls ( P < 0.001). This study demonstrated that sequence analyses can correlate well with epidemiological findings and confirm the value of the molecular approach for linked infections of HBV through heterosexual contact between spouses. Susceptible adults should receive vaccination.     

A clinical study on pseudomyxoma peritonei

Abstract To elucidate the clinical entity of pseudomyxoma peritonei, nine patients (male: female = 6:3) who had been treated in Chang Gung Memorial Hospital in the past 13 years were reviewed. The male patients with original appendiceal tumour were older than the male patients with original colon cancer or indefinite tumour (70, 67 and 67 years vs 42, 27 and 50 years). In addition, the former group survived in a disease-free status for 28 months on average, while the latter group died within 2 years. Echogenic ascites and diffuse low-attenuation intra-abdominal masses with scalloping on the surface of liver detected by ultrasonography and by computerized tomography, respectively, were found in most of the patients. Elevation of the serum carcinoembryonic antigen (CEA) during recurrence of the disease was also noted. This series suggested that: (i) the pre-operative diagnosis could be made with careful physical examination in conjunction with sonography or computerized tomography; (ii) the prognosis was better in patients with tumour of appendiceal origin; and (iii) serum CEA might be valuable for early detection of recurrence.     

The molecular aetiology of haemophilia A in a New Zealand patient group

The genetic basis of haemophilia A (HA) is well-established, and many haematology services are supported by molecular biology laboratories that offer factor VIII genetic testing for HA patients. This report describes the results from factor VIII gene (F8) analysis of a New Zealand cohort of 45 proband HA patients. We screened all proband HA patients attending local clinics to determine the molecular basis of disease in each case. We also aimed to evaluate the significance of founder effect in this population and to explain an unusual case of HA in a female patient. HA patients were screened for the common F8 gene inversion mutations using previously described PCR-based techniques, and for single base substitution mutations using denaturing high performance liquid chromatography and DNA sequencing. Analysis of microsatellite markers located within or near F8 was used to determine identity by descent and trace inheritance patterns of disease alleles. X-chromosome inactivation (XCI) patterns were detected using methylation specific PCR. Pathogenic F8 gene mutations were detected in all 45 HA patients in this cohort and non-random XCI was confirmed in a female haemophiliac. We report nine novel F8 mutations, including two splicing mutations, a five nucleotide deletion and a large deletion at the 5' end of the gene. The molecular aetiology of HA was similar to that described in other studies but the distribution of mutations was unusual due to founder effects, with almost a quarter of all probands being descended from just three individuals.     

Feto-maternal surveillance in labour: a new approach with an on-line microcomputer

Summary. A new method of real-time computer surveillance during labour is described with a commercially available'low-cost' microcomputer and integral video display unit (VDU). The fetal monitoring program gives accurate and reliable information on eight parameters of fetal and maternal wellbeing, four of which may be displayed simultaneously, with the facility of instant data recall. Emphasis is on simplicity of operation, and clarity of data display in the form of horizontal bar graphs updated at 5-min intervals, with most recent information in numerical form. Flexibility of the system enables program modification with relative ease, and adaptation to two unmodified commercial electronic fetal monitors.     

抗疟药物的研究 Ⅰ.4-羟基-7-氯喹啉酸制备的改進

抗疟药氯喹生产的重要中间体——4-羟基-7-氯喹啉酸(Ⅴ),原用的甲脒法,缩合收率很低。经改进,加原甲酸乙酯参与反应,并找到硝酸铵为有效催化剂,控制适当的反应条件,从间氯苯胺至Ⅴ的四步反应,总收卒为75—80%。即单批的收率较原法提高了5倍以上。经推广到生产上,解决了主要技术关键,与现有各生产路线相较,有其独特的先进性。     

Assessment of serum and bile levels of CA19-9 and CA125 in cholangitis and bile duct carcinoma

In this study, CA19-9 and CA125 in serum and bile were measured to evaluate their diagnostic value in cholangitis and bile duct carcinoma. Patients were classified into three groups: group A, the control group, had cholelithiasis without infection (n = 23), group B had acute cholangitis (n = 25) and group C had bile duct carcinoma without bacterial infection (n = 18). All patients had undergone surgery, and bile and serum of the patients were measured for the two tumour markers by radio-immunoassay. The positivity rate for serum CA19-9 was 4.4% in the control group, 28.0% in group B and 61.1% in group C. The positivity rates for serum CA125 in groups control, B and C were 0%, 4% and 27.78% respectively. The diagnostic accuracy for bile duct carcinoma was 67.4% for both CA19-9 or CA125. The concentration of CA19-9 in bile was more than 1200 ng/mL in 72% of patients with acute cholangitis, in 61.1% of all patients with bile duct carcinoma and 0% in the control group. The frequency of concentrations of CA125 in bile greater than 200 ng/mL was 38.89% in bile duct carcinoma and none was observed in the control or acute cholangitis groups. In conclusion, the concentration of CA19-9 was increased not only by the tumour itself, but also by infection. In the diagnosis of bile duct carcinomas, the sensitivity of CA125 was low but its specificity was very high.     

Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: Incidence and risk factors

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trials were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to IFNα-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P <0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3–6.6; P <0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2–32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.