The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence.

BACKGROUND & AIMS: We conducted a systematic review and a meta-analysis to estimate the magnitude and determinants of association between diabetes and hepatocellular carcinoma (HCC). METHODS: MEDLINE searches were conducted for published full studies (between January 1966 and February 2005) that provided risk estimates and met criteria concerning the definition of exposure and outcomes. Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were synthesized using a random-effects model. RESULTS: A total of 26 studies met our inclusion and exclusion criteria. Among 13 case-control studies, diabetes was associated significantly with HCC in 9 studies (pooled odds ratio, 2.5; 95% confidence interval, 1.8-3.5). Among 13 cohort studies, diabetes was associated significantly with HCC in 7 studies (pooled risk ratio, 2.5; 95% confidence interval, 1.9-3.2). The results were relatively consistent in different populations, different geographic locations, and a variety of control groups. The significant association between HCC and diabetes was independent of alcohol use or viral hepatitis in the 10 studies that examined these factors. Few studies adjusted for diet and obesity. CONCLUSIONS: Diabetes is associated with an increased risk for HCC. However, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity.     

Regulation of autoimmune response

Recent work on such apparently disparate fields as T-cell receptor peptide-induced regulation, superantigens, antigen-induced tolerance, models of peripheral tolerance, apoptosis, and T-cell receptor antagonists demonstrates a similarity in immune response from a regulatory perspective. In many systems, a ‘tolerance’ pathway is observed, characterized broadly as an initial disturbance in the immune system, with a resulting predominance of effector cells, followed by a homeostatic response (often requiring CD8⁺ cells) which leads the effector population into T-cell receptor downregulation, T-cell inactivation, anergy and, often, eventual apoptotic death. In the regulated immune response, mixed populations of anergized and apoptosing T cells can be found. In some cases, anergy appears to lead to death while, in other instances, cells revert to a functional state. This review focuses on recent papers examining each of these topics in an attempt to obtain a preliminary, integrated picture of immune regulation in autoimmune diseases.     

Normal splenic function in children with the nephrotic syndrome

Children with the idiopathic nephrotic syndrome (NS) are known to be susceptible to bacterial infections. A recent report suggested that splenic hypofunction may be responsible for this immunological defect. We assessed splenic function by counting the circulating pocked red blood cells (PkRBCs) using interference phase contrast microscopy. PkRBCs are removed by the spleen, so that normal eusplenic individuals have less than 2% PkRBCs while asplenics have 15%–30%. Intermediate values are seen in hyposplenism. Thirty-three measurements of PkRBCs were made in 19 children with NS (mean age 7.5±0.8 years). PkRBCs were normal in all children tested (range 0–0.8%), including two patients with bacterial peritonitis associated with relapse. Thus we were unable to find evidence of hyposplenism in children with NS.     

Cerebral hemodynamic and metabolic profiles in fulminant hepatic failure: relationship to outcome.

The purpose of this retrospective study was to examine the potential role of cerebral hemodynamic and metabolic factors in the outcome of patients with fulminant hepatic failure (FHF). Based on the literature, a hypothetical model was proposed in which physiologic changes progress sequentially in five phases, as defined by intracranial pressure (ICP) and cerebral blood flow (CBF) measurements. Seventy-six cerebral physiologic profiles were obtained in 26 patients (2 to 5 studies each) within 6 days of FHF diagnosis. ICP was continuously measured by an extradural fiber optic monitor. Global CBF estimates were obtained by xenon clearance techniques. Jugular venous and peripheral artery catheters permitted calculation of cerebral arteriovenous oxygen differences (AVDO2), from which cerebral metabolic rate for oxygen (CMRO2) was derived. A depressed CMRO2 was found in all patients. There was no evidence of cerebral ischemia as indicated by elevated AVDO2s. Instead, over 65% of the patients revealed cerebral hyperemia. Eight of the 26 patients underwent orthotopic liver transplantation-all recovered neurologically, including 6 with elevated ICPs. Of the 18 patients receiving medical treatment only, all 7 with increased ICP died in contrast to 9 survivors whose ICP remained normal (P < 0.004). Hyperemia, per se, was not related to outcome, although it occurred more frequently at the time of ICP elevations. Six patients were studied during brain death. All 6 revealed malignant intracranial hypertension, preceded by hyperemia. In conclusion, the above findings are consistent with the hypothetical model proposed. Prospective longitudinal studies are recommended to determine the precise evolution of the pathophysiologic changes.