Co-occurring hepatitis C, substance use, and psychiatric illness: Treatment issues and developing integrated models of care

Hepatitis C virus (HCV) infection is transmitted by injection drug use and associated with psychiatric conditions. Patients with drug use or significant psychiatric illness have typically been excluded from HCV treatment trials noting the 1997 National Institutes of Health Consensus Statement on HCV that indicated active drug use and major depressive illness were contraindications to treatment of HCV infection. However, the 2002 NIH Consensus Statement recognized that these patients could be effectively treated for HCV infection and recommended that treatment be considered on a case-by-case basis. Treating HCV infection in these patients is challenging, with drug use relapse possibly leading to psychosocial instability, poor adherence, and HCV reinfection. Interferon therapy may exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency virus or hepatitis B virus provide additional challenges, and access to ancillary medical and psychiatric services may be limited. Patients with co-occurring HCV infection, substance use, and psychiatric illness can complete interferon treatment with careful monitoring and aggressive intervention. Clinicians must integrate early interventions for psychiatric conditions and drug use into their treatment algorithm. Few programs or treatment models are designed to manage co-occurring substance use, psychiatric illness, and HCV infection and therapy. The National Institute on Drug Abuse convened a panel of experts to address the current status and the long-range needs through a 2-day workshop, Co-occurring Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and Developing Integrated Models of Care. This conference report summarizes current data, medical management issues, and strategies discussed.     

Plant sterols and cardiovascular disease: a systematic review and meta-analysis

The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four case-control, five nested case-control, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD.     

Serum perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) concentrations and liver function biomarkers in a population with elevated PFOA exposure

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes.Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults.Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), γ-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed.Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels.Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.     

The thiamine status of adult humans depends on carbohydrate intake

Thiamine requirements for humans are generally expressed as absolute values per day (mg/d) or in relation to total caloric intake. Limited data are available on the relation between thiamine requirements and the intake of carbohydrates. This study was performed to investigate the influence of stepwise increases of carbohydrate intake on the status of thiamine in healthy volunteers under isocaloric conditions. During an adaptation phase of four days, the carbohydrate intake of twelve healthy volunteers (6 male, 6 female) was 55% of total energy intake. During the subsequent intervention periods, carbohydrate intake was increased to 65% of total energy for four days and to 75% for another four days. Thiamine intake, total energy intake, and physical activity were kept constant throughout the study. HPLC analysis was used to measure thiamine in plasma, urine and feces. Erythrocyte transketolase activity (ETK) was determined enzymatically. During the intervention periods thiamine decreased significantly (p < 0.05) in plasma (from 19.3 +/- 3.3 to 16.4 +/- 4.0 nmol/l) as well as in urine (from 72 +/- 56 to 58 +/- 21 mumol/mol creatinine). ETK and feces content of thiamine remained unchanged. An increase of dietary carbohydrate intake from 55% to 65% and 75%, respectively, of total caloric intake for four days per period at isocaloric conditions causes a decrease of plasma and urine levels of thiamine without affecting enzyme activities.     

Fasting levels of glicentin are higher in Roux-en-Y gastric bypass patients exhibiting postprandial hypoglycemia during a meal test

Background

Post-bypass postprandial hypoglycemia (PPH) is a frequent complication of Roux-en-Y Gastric Bypass (RYGB) but predictors remain poorly identified and are needed to assess individual risk. After RYGB, exaggerated secretion of glucagon-like peptide-1 (GLP-1) and insulin could lead to PPH, but other proglucagon-derived peptides, including glicentin and glucagon, could also contribute to this phenomenon.