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Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5-year age groups, sex, and year of diagnosis. Information on risk factors was collected by personal interview and medical records review. Blood samples were tested for the presence of antibodies to hepatitis C virus antigen (anti-HCV), hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (anti-HBc). Conditional logistic regression was used to determine odds ratios (ORs) by the maximum likelihood method. Multivariate ORs and 95% confidence intervals (CIs) were 15.3 (4.3-54.4), 12.6 (2.5-63.1), 4.5 (1.4-14.8), and 4.3 (1.9-9.9) for anti-HCV, HBsAg, heavy alcohol consumption (>/=80 mL ethanol/d), and diabetes mellitus, respectively. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection (OR, 53.9; 95% CI, 7.0-415.7) and diabetes mellitus (OR, 9.9; 95% CI, 2.5-39.3). Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32%), whereas 22%, 16%, and 20% were explained by HCV, HBV, and diabetes mellitus, respectively. In conclusion, the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new HCC prevention strategies in high-risk individuals.
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PMID:Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. 1239 12

Chronic infection with hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC). In general, HCC develops only after 2 or more decades of HCV infection and the increased risk is restricted largely to patients with cirrhosis or advanced fibrosis. Factors that predispose to HCC among HCV-infected persons include male sex, older age, hepatitis B virus (HBV) coinfection, heavy alcohol intake, and possibly diabetes and a transfusion-related source of HCV infection. Viral factors play a minor role. The likelihood of development of HCC among HCV-infected persons is difficult to determine because of the paucity of adequate long-term cohort studies; the best estimate is 1% to 3% after 30 years. Once cirrhosis is established, however, HCC develops at an annual rate of 1% to 4%. Successful antiviral therapy of patients with HCV-related cirrhosis may reduce the future risk for HCC. The incidence of and mortality caused by all HCC has doubled in the United States over the past 25 years, an increase that has affected all ethnic groups, both sexes, and younger age groups. Given the current prevalence of HCV infection among persons 30 to 50 years of age, the incidence and mortality rates of HCC are likely to double in the United States over the next 10 to 20 years. Future research should focus on improving understanding of the incidence and risk factors for HCC, causes of HCV-related carcinogenesis, means of early detection, and better treatment for HCC.
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PMID:Hepatocellular carcinoma and hepatitis C in the United States. 1240 79

The safety and efficacy of current vaccines are reviewed for high-risk populations, such as those with underlying medical conditions or occupational or lifestyle circumstances. The morbidity and mortality from vaccine-preventable diseases are high among persons with underlying medical conditions; thus, influenza and pneumococcal polysaccharide vaccines are recommended for those with cardiac disease, diabetes mellitus, or chronic obstructive pulmonary disease. For the same reasons, influenza vaccine is recommended for pregnant women and for persons with asthma. Health-care workers are at risk for acquiring and transmitting hepatitis B, measles, and influenza; hence, vaccination against these diseases is recommended.
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PMID:Vaccines for persons at high risk due to medical conditions, occupation, environment, or lifestyle, 2003. 1255 76

Despite the abundance of reports concerning the increased frequency of diabetes and impaired glucose tolerance in chronic liver diseases, the mechanisms underlying this phenomenon have not been resolved. 30 patients with hepatitis C virus (HCV) infection and 17 with hepatitis B virus (HBV) infection who showed an altered responds to a standard oral glucose tolerance test were investigated in order to evaluate their pancreatic-endocrine features. We have also evaluated 40 patients (20 with HCV infection and 20 with HCB infection) who developed diabetes after diagnosis of liver disease. Patients with HBV infection showed signs of enhanced insulin resistance but overt diabetes develops in those who, in addition to insulin insensitivity, have a relative defect of insulin secretion. In patients with HCV infection the significantly lower plasma insulin and C-peptide levels suggest that impairment of insulin secretion is the main mechanism leading to both glucose intolerance and overt diabetes.
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PMID:[The pathological mechanisms of glycoregulation disturbances in chronic hepatitis B and C]. 1263 77

Engerix-B (Hep-B[Eng]) is a noninfectious recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg). It is produced from genetically engineered yeast (Saccharomyces cerevisiae). Intramuscular Hep-B(Eng) [0-, 1-, 6-month schedule] has excellent immunogenicity in healthy neonates and infants, children, adolescents and adults, with seroprotection rates of 85-100% seen approximate, equals 1 month after the final dose of vaccine; seroprotection was defined as an antibody against HBsAg (anti-HBs) titre of > or =10 IU/L. The use of alternative Hep-B(Eng) immunisation schedules (e.g. a 0-, 1-, 2-, 12-month schedule in neonates and infants, 0-, 12-, 24-month or two-dose schedules in children and adolescents, and accelerated schedules in adults) have also been associated with high rates of seroprotection. Seroprotection rates were generally similar with Hep-B(Eng) and the recombinant vaccine Recombivax HB (Hep-B[Rax]) or plasma-derived vaccines (PDVs) approximate, equals 1 month after the final dose (although anti-HBs geometric mean titres were significantly higher with Hep-B[Eng] than with Hep-B[Rax]). One month after the final dose, adults had significantly higher seroprotection rates with the recombinant triple-antigen vaccine Bio-Hep-B (Hep-B[Bio]) than with Hep-B(Eng), although seroprotection rates in healthy infants were similar with Hep-B(Eng) and Hep-B(Bio). Hep-B(Eng) had excellent immunogenicity in several groups considered at high risk of acquiring hepatitis B (e.g. neonates born to hepatitis B carrier mothers and healthcare workers). The immunogenicity of Hep-B(Eng) was reduced in patients with conditions associated with impaired immune function (e.g. patients undergoing haemodialysis or being treated for malignancy), although it had good immunogenicity in patients with diabetes mellitus.Hep-B(Eng) had excellent protective efficacy against HBsAg carriage in healthy infants and children, and in neonates born to hepatitis B carrier mothers (protective efficacy of 95-99%). Hep-B(Eng) also demonstrated good protective efficacy in a number of other high-risk groups. Hep-B(Eng) is generally well tolerated with a tolerability profile similar to that of Hep-B(Rax), Hep-B(Bio) and PDVs. In conclusion, Hep-B(Eng) is a well established, highly immunogenic hepatitis B vaccine with good tolerability and excellent protective efficacy; it offers flexibility through a variety of immunisation schedules. In addition, it appears that Hep-B(Eng) confers immunity for at least 10 years. Hep-B(Eng) has an important role in mass vaccination campaigns against hepatitis B, as well as in groups considered at high risk of acquiring hepatitis B.
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PMID:Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B. 1269 2

The effects of adding rosiglitazone to existing sulfonylurea (SU) treatment have not previously been studied in Chinese patients with type 2 diabetes and no known pre-existing hepatic impairment. Patients were randomized to receive rosiglitazone 2 mg twice daily (R4 + SU) or 4 mg twice daily (R8 + SU) or placebo (SU + P) for 24 weeks in addition to existing SU treatment. Most patients were taking concomitant glibenclamide (34%) or gliclazide (25%). Changes in glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), and plasma insulin concentrations were measured. Of the 530 patients enrolled (45% male, mean age 59 years), 105 were in the SU + P group, 215 in the R4 + SU group, and 210 in the R8 + SU group. The mean baseline HbA(1c) was 9.8%, and FPG was 183.8 mg/dL. Compared with placebo, addition of rosiglitazone (2 or 4 mg twice daily) produced significant decreases in mean HbA(1c) (1.04% and 1.44%, respectively; p < 0.0001) and FPG (21.6 and 36.0 mg/dL, respectively; p < 0.0001). There were statistically significant (p < 0.0001) reductions from baseline in insulin concentration of 23.3 and 30.4 pmol/L in the R4 + SU and R8 + SU groups, respectively. Despite the high prevalence of seropositivity for hepatitis B and/or C at baseline (56%), there was no evidence of hepatotoxicity. No clinically significant changes in routine hematology, biochemistry, or electrocardiogram were observed. The addition of rosiglitazone to SU produced clinically significant improvements in glycemic control in Chinese patients with type 2 diabetes. Rosiglitazone plus SU was well tolerated irrespective of hepatitis B and C serological status.
Diabetes Technol Ther 2003
PMID:Addition of rosiglitazone to existing sulfonylurea treatment in chinese patients with type 2 diabetes and exposure to hepatitis B or C. 1272 6

A high prevalence of type 2 diabetes mellitus in patients with hepatitis C virus (HCV)-related chronic liver diseases has been reported in numerous studies. Other studies failed to confirm this observation. We have studied the relative prevalence of type 2 diabetes mellitus in two groups of patients respectively presenting with HCV-related chronic liver disease (224 patients) and chronic liver diseases of other etiologies (30 hepatitis B virus-HBV-related chronic liver disease, 22 alcoholic liver cirrhosis), in order to confront them. Our study revealed a higher prevalence of diabetes mellitus in the group of patients with HCV-related chronic liver disease in comparison with the group of patients with chronic liver disease of other etiologies (32.5 vs 15.3%; p = 0.03). Patients with HBV-related liver disease had diabetes in 6.6% of cases, and the difference with patients with HCV-related disease was significant (p = 0.007). Our study confirms a higher prevalence of type 2 diabetes mellitus in patients with HCV-related chronic liver disease. It could be suggested that type 2 diabetes mellitus in patients with HCV-related chronic liver disease could be facilitated by hepatic iron overload and mitochondrial damage.
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PMID:[Prevalence and significance of type-2 diabetes mellitus in chronic liver disease, correlated with hepatitis C virus]. 1273 22

Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology. These similarities in the literature suggested the exploration of lipids in sera of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which is typically used for screening ciguateric ocean fish. Sera from patients with other diseases, including hepatitis B, cancer, and diabetes, were included to assess the degree of specificity involved. Sera were treated with acetone in a ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted acetone fraction of the 37 normal showed +/- activity to +activity with 16 no titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40 titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer, 50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or =1:40 titer. Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These data are summarized in Fig. 1. As shown in Table 1, a significant increase (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal group. A preliminary chemical study in C18 octadecylsilyl columns showed all fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol, and 100% methanol) to contain lipids reactive to MAb-CTX with different intensities. Prostaglandins were shown in 100% methanol fraction. Competitive MIA with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope suggested similarities in structure with ciguatoxin. This was compatible with the neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1, chloroform : methanol solvents.
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PMID:Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX. 1278 62

Hepatitis B vaccines (HBVs) are composed of highly purified preparations of hepatitis B virus surface antigen (HBsAg). An adjuvant, either aluminium phosphate or aluminium hydroxide, is added to the vaccines, which are sometimes preserved with thiomersal. In placebo-controlled studies, common side effects other than local reactions were reported no more frequently among vaccine recipients than among individuals receiving a placebo. A number of controversial adverse events have, however, been purported to be associated with HBVs, including rheumatoid arthritis (RA), diabetes, demyelinating diseases (e.g., multiple sclerosis [MS]), chronic fatigue syndrome, and more recently, lymphoblastic leukaemia. In addition, the safety of the thiomersal and aluminium contained in the vaccine has also been under close scrutiny. These issues have been reviewed by a number of country-specific or international independent review committees such as that of the US Institute of Medicine (IOM) and the World Health Organization's (WHO) Global Advisory Committee on Vaccine Safety (GACVS). Upon review of the scientific evidence, none of the serious allegations have so far been confirmed. On the contrary, scientific evidence has accumulated to disprove many of the allegations. In particular, the IOM committee has concluded that the evidence favoured rejection of a causal relationship between HBV administered to adults and incident MS or MS relapse. Whilst it is important to continue monitoring some of the safety issues, there is no evidence to suggest that the WHO should consider altering its recommendation that all countries should have universal infant and/or adolescent immunisation programmes. The risks of hepatitis B vaccination are only theoretical in comparison with clear benefits in terms of cirrhosis and cancer prevention, and the HBV remains one with an excellent safety profile.
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PMID:Safety of immunisation and adverse events following vaccination against hepatitis B. 1290 2

Patients on chronic haemodialysis (PCHD) respond less well to vaccination with recombinant hepatitis B virus superficial antigen (HbsAg) because of immunity disorders in uraemic patients. Today many schemes and vaccination modification for nonresponding PCHD are proposed. The reaction on vaccination with HbsAg is weaker in those PCHD who had diabetes, older age and insufficient nutritive parameters. In those patients some alternative schemes of vaccinating for nonrespondering PCHD must be considered, especially one of the proposed intradermal ways of vaccine inoculation.
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PMID:[Hepatitis B vaccination in patients on chronic hemodialysis]. 1453 68


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