No abstract

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preSj), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P < 0.001 and P < 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P < 0.05 and P < 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS, either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two-to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations. (J. Clin. Invest. 1992.89:87-96.)

Treatment effect has declined over time in MDD trials, and there has been a high failure rate for these trials during the entire period, but the reasons for these findings remain elusive. Baseline disease severity seems to be a more important factor in study outcome than study duration, dosing regimen, sample size, time when studies were conducted, and regions where data were generated. Close attention is needed to a variety of factors in the design and conduct of these studies, including patient population, diagnostic considerations, patient assessment, and clinical practice differences. These considerations become increasingly important as globalization of clinical trials continues to increase.

To investigate the carcinogenic effect of environmental aflatoxin exposure, 56 cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1995 were identified and individually matched by age, sex, residence and date of recruitment to 220 healthy controls from the same large cohort in Taiwan. Blood samples were analyzed for hepatitis B and C viral markers and for aflatoxin-albumin adducts; urine was tested for aflatoxin metabolites. We obtained information about sociodemographic characteristics, habitual alcohol drinking, cigarette smoking and diet in a structured interview. Hepatitis B virus surface antigen (HBsAg) carriers had a significantly increased risk for HCC. After adjustment for HBsAg serostatus, the matched odds ratio (ORm) was significantly elevated for subjects with high levels of urinary aflatoxin metabolites. When stratified into tertiles, a dose-response relationship with HCC was observed. The ORm for detectable aflatoxin-albumin adducts was not significant after adjustment for HBsAg serostatus. HBsAg-seropositive subjects with high aflatoxin exposure had a higher risk than subjects with high aflatoxin exposure only or HBsAg seropositivity only. In male HBsAg-seropositive subjects, adjusted ORs were 2.8 (95% confidence interval [CI] = 0.9-9.1) for detectable compared with non-detectable aflatoxin-albumin adducts and 5.5 (CI = 1.3-23.4) for high compared with low urinary aflatoxin metabolite levels. Our results suggest that environmental aflatoxin exposure may enhance the hepatic carcinogenic potential of hepatitis B virus. A large-scale study will be needed to evaluate the effect of aflatoxin exposure on HBsAg non-carriers.

No abstract

Although previous studies have demonstrated the ability of ultrasonography (US) screening to detect small asymptomatic hepatocellular carcinoma (HCC), the efficacy of US screening in reducing deaths from HCC still remained unresolved. A 2-stage screening program was designed to identify a high risk group in 7 townships in Taiwan by 6 markers (of risk for HCC) and repeated US screening was further applied to those with at least 1 positive result for the 6 markers, with a range of 3-to 6-month inter-screening intervals to those with liver cirrhosis or other chronic liver diseases and an annual screening regime for the remaining subjects with normal findings according to US. The 4,843 subjects in this cohort were followed up for an average of 7 years. We compared 4,385 attenders with 458 non-attenders, in conjunction with baseline assessment for self-selection bias. In addition, we assessed baseline variables with respect to their effects on risk of incidence of and mortality from HCC and on risk of incidence of liver cirrhosis. The difference in mortality between attenders and non-attenders was then re-estimated adjusting for significant predictors of cirrhosis, HCC incidence and HCC death as a further guard against baseline differences between attenders and non-attenders in risk profiles. Results of US screening for this high risk group found the mortality was lower by 24% (95% CI: ؊52 to 62%) in the attenders compared to the non-attenders. After adjustment for sensitivity, the mean sojourn time (MST) were 1.57 (95% CI: 0.94 -4.68) for subjects with liver cirrhosis and 2.66 (95% CI: 1.68 -6.37) years for non-cirrhotic patient. Significant increases in risk of HCC incidence were associated with increasing age, male gender, hepatitis B surface antigen positive (HbsAg), hepatitis C antibody positive (Anti-HCV), high levels of alanine transaminase (ALT) and alpha-fetoprotein (AFP) and a family history of HCC. Significantly increased risks of liver cirrhosis were associated with predictors of cirrhosis were increasing age, HbsAg, high levels of ALT and of AFP. Significant or borderline significant increases in risk of HCC death were associated with increasing age, male gender, HbsAg, high levels of AST and AFP. Adjusted for the significant variables, the mortality was lower by 41% (95% CI: ؊20 to 71%, p ‫؍‬ 0.1446) in the attenders compared to the non-attenders. The present study provides suggestive evidence on the efficacy of US screening in a selective high risk group in an endemic area of hepatitis B. A randomized controlled trial would yield definitive evidence. Within the protocol of such a trial, a shorter interscreening interval for patients with liver cirrhosis is suggested.

Peritoneal metastases of HCC are rare and can occur synchronously or metachronously. Though increased long-term survival was found in patients who had surgical removal of peritoneal metastases, the main determinant of better survival is Child-Pugh grade.

Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.