Adipokines and melanocortins in the hepatic manifestation of metabolic syndrome: nonalcoholic fatty liver disease

Metabolic syndrome is associated with nonalcoholic fatty liver disease and its more aggressive form, nonalcoholic steatohepatitis. Adipokines produced by white adipose tissue possess broad physiological activity and play an important autocrine role in obesity-associated complications, including metabolic syndrome, nonalcoholic fatty liver disease and cardiovascular disease. Various adipokines may have beneficial or harmful effects. Other tissues, particularly stomach and intestine, produce active molecules that can influence the function of adipocytes and, possibly, the levels of adipokine secretion. In some cases, the production sites of these molecules remain unknown. The review focuses on our current understanding of the disease-related effects of the adipokines and the melanocortins on various peripheral tissues, and discusses some of their potential interactions with each other. Potential therapeutic applications are also considered.     

Anger experiences among hepatitis C patients: relationship to depressive symptoms and health-related quality of life

The authors examined anger among hepatitis C (HCV) patients and its relationship to health-related quality of life (HRQL) and depression. Eighty-seven HCV patients who received pegylated interferon-alpha(2b) and ribavirin were included. Patients' mean age was 48 years; 42% were women, and 60% were white. Patients experienced moderate anger while undergoing HCV treatment. Angry feelings increased during treatment in some domains, specifically, Control Over Anger and Angry Reaction. Greater anger was associated with more depression and poorer HRQL. Findings point to the importance for physicians to screen for a wide range of neuropsychiatric side effects of interferon, including anger.     

Cholestatic liver diseases and health-related quality of life

OBJECTIVE: Symptoms associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) negatively affect health-related quality of life (HRQL). The aim of this study was to measure HRQL in patients with chronic cholestatic liver diseases and to determine factors associated with more severe impairment. METHODS: We conducted a cross-sectional study in which we documented patients' demographic and clinical characteristics, and measured their HRQL using the Short Form-36 and Chronic Liver Disease Questionnaire. We assessed the association of HRQL impairment with disease severity (Child's-Pugh class and Mayo PBC Risk Score) and compared patients' HRQL with those of a healthy population, and patients with congestive heart failure, chronic obstructive pulmonary disease, and diabetes. RESULTS: One hundred and four patients with PBC and PSC participated, of whom 73% were women, with an average age of 55+/-12 yr. Of these patients, 61% had cirrhosis (37% Child's A, 23% Child's B, and 2% Child's C). Patients with cholestatic liver disease showed more HRQL impairment than the healthy population and were similar to patients with other chronic conditions. Additionally, patients who experienced severe itching showed profound HRQL impairment. In patients with PBC, Physical Component Summary (PCS) scores of the SF-36 and Chronic Liver Disease Questionnaire (CLDQ) scores fell from noncirrhotic to Child's A to Child's B/C and with worsening Mayo PBC Risk Scores. No other clinicodemographic data were associated with patients' well-being. CONCLUSIONS: Patients with cholestatic liver disease (PBC and PSC) showed substantial impairment of HRQL, which is further affected by worsening disease severity. Disease-specific measures were better able to discriminate patients with varying severities.     

Health-related quality of life in chronic liver disease: the impact of type and severity of disease

OBJECTIVE: The type and severity of chronic liver disease may have different effects on health-related quality of life (HRQL). The aim of our study was to determine whether HRQL in patients with chronic liver disease differs by type and severity of disease and to identify which clinical and physiological factors affect this impairment. METHODS: In this study, HRQL was measured with a generic (Short Form 36) and a liver disease-specific (Chronic Liver Disease Questionnaire) questionnaire. Clinical, demographic, and laboratory data were collected at office visits. Patient's HRQL scores were compared with the published norms and to the chronically ill populations. A total of 353 patients (mean age 50 yr, 51% men) with chronic liver disease, either viral disease (hepatitis B and C), cholestatic disease (primary biliary cirrhosis or primary sclerosing cholangitis), or hepatocellular disease were enrolled in the study. RESULTS: In general, HRQL in patients with chronic liver disease was lower than the normal population and was similar to that of patients with chronic obstructive pulmonary disease or congestive heart failure. In cirrhotic patients, some dimensions of HRQL were less impaired in patients with cholestatic disease than in those with hepatocellular diseases. More severe disease (higher Child's class) was associated with a lower Chronic Liver Disease Questionnaire score and the Short Form 36's physical component summary scores. Older age had a weak negative association with the physical aspects of HRQL. CONCLUSIONS: We conclude that chronic liver disease substantially reduces HRQL, and this impact does not differ markedly by type of disease. Older age and measures of disease severity were associated with poorer HRQL.     

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation

Type IIB von Willebrand disease is characterized by enhanced ristocetin- induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.     

Ultrasound-Guided Liver Biopsy for Parenchymal Liver Disease (An Economic Analysis)

The use of ultrasound (US) to assist in liverbiopsy for nonfocal liver disease has been shown tosignificantly decrease the incidence of minorcomplications (defined as pain requiring treatment,hypotension, or bleeding). In this study, decision analysiswas used to estimate the average additional net chargefor US guidance. The risks for minor and majorcomplications were extracted from the literature. The incidence of minor complications such as painand bleeding not requiring hospitalization has beenreported as 49% for blind liver biopsy and 39% forUS-guided liver biopsy. Major complications requiring hospital admission occur in 4% of blind liverbiopsies and 2% of US-guided liver biopsies. A decisiontree was used to calculate the total charges of liverbiopsy and its associated complications. The charge for treating an episode of minor complicationswas estimated at $605. The charge related to an episodeof major complications was estimated at $1533. The totalcharge for an ultrasoundguided liver biopsy (except the added charge for the use ofultrasound) was $1770, or $102 less than the same chargefor blind liver biopsy. The addition of ultrasound inperforming liver biopsies for diffuse parenchymal liver disease is cost-saving if the additional chargeof US is less than $102.     

Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study.

A randomized, double-blind, dose-escalation study evaluated the safety and efficacy of hepatitis C virus (HCV)-Ab(XTL)68, a neutralizing, high-affinity, fully human, anti-E2 monoclonal antibody, in 24 HCV-positive patients undergoing liver transplantation. HCV-Ab(XTL)68 or placebo was administered at doses from 20-240 mg as 2-4 infusions during the first 24 hours after transplantation, followed by daily infusions for 6 days, weekly infusions for 3 weeks, and either 2 or 4 weekly infusions for 8 weeks. Serum concentrations of total anti-E2 obtained during daily infusions of 120-240 mg HCV-Ab(XTL)68 were 50-200 microg/mL above concentrations in the placebo group. Median serum concentration of HCV RNA dropped below baseline in all groups immediately after transplantation. On day 2, median change from baseline in HCV RNA was -1.8 and -2.4 log in the 120-mg and 240-mg groups, respectively, compared with -1.5 log with placebo. The difference was lost after day 7 when the dosing frequency was reduced. The coincidence of increases in anti-E2 with decreases in HCV RNA concentration indicate that the dose-related changes in HCV RNA concentration were a result of HCV-Ab(XTL)68 administration in the 120- and 240-mg groups. The overall incidence of nonfatal serious adverse events was higher with placebo (60%) vs. all active treatments combined (42%). In conclusion, HCV-Ab(XTL)68 may decrease serum concentrations of HCV RNA in patients after liver transplantation. Studies evaluating more frequent daily dosing at doses >120 mg are necessary to investigate sustained viral suppression in this population.