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.     

Molecular cloning of cDNA coding for the 68 kDa allergen of Penicillium notatum using MoAbs

To characterize the 68 kDa allergen of Penicillium notatum (also known as P. chrysogenum), a molecular antibody (MoAb) (P40) was previously generated. For cDNA cloning, three more MoAbs (3F, 5A3, 5G2) were generated in the present study. A mixture of all the four MoAbs was used in cloning of the gene coding for the 68 kDa allergen from a λgt11 cDNA library of P. chrysogenum. A cDNA clone (A6) with DNA insert of about 0.5 kb which encodes for the 3′-terminal nucleotide sequence of the 68 kDa allergen was obtained. The cloned sequence contained two putative N-glycosylation sites. The reduction in molecular weight from 68 to 62 kDa in immunoblotting after treatment of the crude extract of P. notatum with N-glycosidase F indicates that the 68 kDa allergen is a glycoprotein. Nucleotide sequence determination showed that 188 (54%) of the 348 nucleotides of the cDNA sequence obtained were identical to the same region of the nucleotide sequence of the beta-N-acetylglucosaminidase gene of Candida albicans. Although the cDNA clone obtained did not encode the full-length gene of the 68 kDa allergen, polypeptide expressed from the A6 cDNA showed positive immunological reactivities to all four MoAbs used in the cloning experiment and to IgE antibodies in sera of asthmatic patients. There was a loss of immunoblotting activity to the 68 kDa component after absorption of MoAb P40-containing culture supernatant with filters blotted on plaque lawns of cDNA clone A6. Moreover, the immunoblotting activity remained when the MoAbs affinity-purified with filters containing polypeptides encoded by the cDNA insert of clone A6 were used. These two observations indicate that clone A6, which encodes 117 amino acid residues of a putative 560-residue polypeptide, is a cDNA clone of the 68 kDa component of P. notatum. In conclusion, results obtained from cloning and characterization of a partial cDNA clone described in this study suggest that the 68 kDa allergen of P. notatum is a beta-N-acetylglucosaminidase.     

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.     

Hepatocellular carcinoma presenting as acute spontaneous haemothorax

Hepatocellular carcinoma may present in various ways, but only a few instances present with symptoms of distant metastases. This report describes a case of hepatocellular carcinoma presenting with acute haemothorax and haemorrhagic shock secondary to spontaneous rupture of chest wall metastasis. Hepatocellular carcinoma is a frequent malignancy in Asia and should be considered in the list of differential diagnosis of spontaneous haemothorax.     

Hepatitis viruses under immunosuppressive agents

Clinical and experimental studies have shown that T cell-mediated immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV) and hepatitis C virus infection. Immunosuppressants may impair T cell function and thereby reduce immune-mediated hepatocytolysis and virus clearance. In addition, corticosteroid may activate the glucocorticoid responsive element in the HBV genome to enhance HBV replication and gene expression. These combined effects result in an increase of viraemia in association with a decrease of serum aminotransferase and hepatic necroinflammation. In acute infection, use of immunosuppressants will increase the incidence of chronic evolution. In chronic infection, withdrawal of immunosuppressants will be followed by a clinical flare due to a rebound of immune attack to hepatocytes with increased viral load. This may lead to a subsequent decrease of the viraemia. Therefore, short-term use of immunosuppressant before antiviral therapy may be beneficial in the treatment of chronic viral hepatitis. However, the clinical rebound may be extremely severe and lead to hepatitis failure; thus, the patients should be monitored closely upon tapering and after the withdrawal of immunosuppressants. Long-term use of immunosuppressants in patients with hepatitis virus infection is usually deleterious, particularly in patients after organ transplantation. These findings suggest that clinicians should be cautious in the use of immunosuppressants in patients with hepatitis virus infection.     

CELL KINETICS, DNA CONTENT AND TSH RECEPTOR-ADENYLATE CYCLASE SYSTEM IN DIFFERENTIATED THYROID CANCER

The purpose of this study was to elucidate the changes of the TSH receptor-adenylate cyclase system in differentiated thyroid carcinomas, and their relationships with nuclear DNA content, cell kinetics and clinical stage. The results showed that the papillary carcinomas had an impaired TSH receptor-adenylate cyclase system. The production of cAMP stimulated by TSH was decreased when compared with non-cancerous tissue and high-affinity TSH receptors were reduced in number or even completely lost (nine in 24 cases). Follicular carcinomas also showed a reduction in, or even complete loss, of high-affinity TSH receptor (one in five cases). However, the responses to the stimulation of TSH, Gpp (NH)p and forskolin were not different from those in non-cancerous tissue. Papillary and follicular cancer cells showed more proliferative activity than those in non-cancerous tissue. Follicular carcinomas contained more hyperploid cells (DNA content greater than 2.5 C) than papillary carcinomas. There were no differences in cell kinetics, DNA content or the effects of Gpp (NH)p or forskolin on adenylate cyclase activity between those papillary carcinomas with high-affinity TSH receptor and those without. However, the presence of high-affinity TSH receptors had higher cAMP generation stimulated by TSH. The patients having papillary carcinomas in the absence of high-affinity TSH receptors were all in clinical stage III. These studies suggest that TSH receptors are the major sites influenced in the TSH receptor-adenylate cyclase system in papillary carcinomas. The TSH receptor-adenylate cyclase system of papillary carcinomas differs more from normal than does that of follicular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Granulomatous hepatitis associated with scrub typhus

A 56 year old patient with scrub typhus infection having unusual presentation of hepatic injury resembling acute hepatitis is described. The clinical features of fever, headache, eschar, lymphadenopathy, lymphocytosis and high Rickettsia tsutsugamushi immunofluorescence titres confirmed the diagnosis of scrub typhus. Acute hepatitis was proven by hepatic biochemical tests and liver biopsy. The patient had a complete recovery soon after antibiotic treatment. The presentation of this case suggests that scrub typhus infection should be included in the list of differential diagnosis of acute hepatitis or granulomatous hepatitis, at least in the Asian Pacific region where scrub typhus still prevails.     

Role of antiviral therapy of HBV in the prevention of cirrhosis and hepatocellular carcinoma

Abstract   Chronic hepatitis B virus (HBV) infection is a serious problem because of its worldwide distribution and potential untoward sequalae such as hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC) may occur. Studies have shown that active HBV replication and resultant hepatitis is the key for disease progression to these untoward sequalae. Successful antiviral therapy using interferon or lamivudine has been shown to halt disease progression, reverse hepatic fibrosis, reduce complications of cirrhosis including HCC and prolong survival. However, the efficacy of antiviral therapy is still not satisfactory. It is urgent to develop strategies for better therapeutic outcomes.