Statin persistence and adherence among older initiators: A nationwide cohort study using the national health insurance claims database in Japan.

PURPOSE: This study clarifies the reality of persistence and adherence to statins in older Japanese people who initiated statin use and compares it between primary and secondary prevention cohorts. METHODS: The nationwide study using the national claims database targeted statin initiators aged ≥55 years from FY2014 to FY2017 in Japan. Persistence and adherence to statins were analyzed overall and according to subgroups based on sex, age stratum, and prevention cohorts. Permissible gap of median days that statins were supplied per prescription to an individual was employed. Persistence rates were estimated as Kaplan-Meier estimates. Poor adherence during persistence was evaluated and defined as <0.8 of the proportion of days covered. RESULTS: Of 3 675 949 initiators, approximately 80% initiated statin use with strong variants. The persistence rate at 1 year was 0.61. Poor adherence to statins during persistence was 8.0% in all patients and this value gradually improved with increasing age. Persistence rate and adherence were lower for the primary prevention cohort than for the secondary prevention cohort, and a notable sex difference was observed for the secondary prevention cohort, which was lower in females but was almost never and slightly observed in the primary prevention cohorts without and with high-risk factors, respectively. CONCLUSIONS: Many statin initiators discontinued statins shortly following statin initiation but adherence while on statin therapy was good. Attentively watching older patients not to discontinue statins and listening to their reasons for discontinuation are required, especially for initiators in primary prevention and females in secondary prevention.

Prognostic factors in patients with hepatocellular carcinoma refractory or intolerant to sorafenib.

OBJECTIVE: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. METHODS: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. RESULTS: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. CONCLUSIONS: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors.

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus-related chronic liver disease.

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.

Efficacy of zinc administration in patients with hepatitis C virus-related chronic liver disease.

OBJECTIVE: Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease (CLD). We therefore examined the effects of zinc administration on inflammatory activity and fibrosis in the liver of patients with HCV-related CLD. MATERIAL AND METHODS: Polaprezinc, a complex of zinc and l-carnosine, was administrated at 225 mg/day for 6 months to 14 patients with HCV-related CLD, in addition to their ongoing prescriptions. Peripheral blood cell counts, liver-related biochemical parameters, serological markers for liver fibrosis, HCV-RNA loads, and serum levels of zinc and ferritin were evaluated before and after zinc administration. RESULTS: Serum zinc concentrations were positively correlated with hepatic reserve before zinc supplementation. A significant increase in serum zinc level was observed after zinc supplementation (64+/-15 versus 78+/-26 mg/dl, p=0.0156). Treatment with polaprezinc significantly decreased serum aminotransferase levels (aspartate aminotransferase (AST): 92+/-33 versus 63+/-23 IU/l, p=0.0004; alanine aminotransferase (ALT): 106+/-43 versus 65+/-32 IU/l, p=0.0002), whereas alkaline phosphatase levels were significantly increased (305+/-117 versus 337+/-118 U/l, p=0.0020). Serum ferritin levels were significantly decreased by treatment with polaprezinc (158+/-141 versus 101+/-80 ng/ml, p=0.0117). The reduction rate of ALT levels by polaprezinc was positively correlated with that of ferritin (r(2)=0.536, p=0.0389). There was a tendency toward a decrease in serum type IV collagen 7S levels after treatment with polaprezinc. However, administration of polaprezinc did not affect peripheral blood cell counts, other liver function tests, or HCV-RNA loads. CONCLUSIONS: These findings suggest that polaprezinc exerts an anti-inflammatory effect on the liver in patients with HCV-related CLD by reducing iron overload.

A role of oxidative stress-generated eicosanoid in the progression of arteriosclerosis in type 2 diabetes mellitus model rats.

Diabetes mellitus (DM) is a well-established risk factor of cardiovascular diseases. We investigated the mechanism of the progression of arteriosclerosis in DM, focusing on the role of oxidative stress and insulin resistance in vivo. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an experimental model of type 2 DM, were assigned to 3 groups, based on supplementation with vitamin E (VE) or troglitazone (TR), a VE-derived agent which improves insulin-resistance. At 36 weeks, plasma and aortic tissue 8-iso-PGF2alpha contents, a vascular proliferating eicosanoid produced in vivo by oxidative stress, were measured by EIA. TGF-beta1 and TGF-beta1 receptor II were immunohistochemically analyzed. Histopathologically, medial area and the nuclear number of smooth muscle cells of the aorta were measured. The tissue 8-iso-PGF2alpha content (pg/g tissue) was significantly decreased by either VE or TR in the aorta (untreated-OLETF, 15,332+/-3,254 vs. TR-treated-OLETF, 7,092+/-1,992 or VE-treated-OLETF, 5,394+/-836, both p<0.01), but that in plasma decreased by only VE. VE and TR improved the increased the level of the actual medial area and the number of smooth muscle cells. The expression of TGF-beta1 was reduced, but TGF-beta1 receptor II was not. 8-iso-PGF2alpha may play an important role in the progression of arteriosclerosis. Antioxidant treatment may promise significant clinical benefits in the early diabetic stage.