Prevalence and outcomes of acute hepatitis B in Okayama, Japan, 2006-2010.

Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p＜0.01), among men who had sex with men (100%, p＜0.005), and among patients having sex with unspecified partners (44.8%, p＜0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A.

Additive improvement induced by bezafibrate in patients with primary biliary cirrhosis showing refractory response to ursodeoxycholic acid.

BACKGROUND AND AIM: Ursodeoxycholic acid (UDCA) has been widely used in the treatment of patients with primary biliary cirrhosis (PBC). However, some patients are refractory to UDCA. The aim of this study is to clarify the additive improvement induced by bezafibrate in patients refractory to UDCA. METHODS: This study was a prospective analysis of 37 consecutive PBC patients. All patients were treated first for 6 months with UDCA, and then with bezafibrate, if their alkaline phosphatase (ALP) levels did not decrease more than 40% or within the normal range after 6 months' treatment with UDCA. Clinical parameters were monitored for the subsequent 24 months. RESULT: Twenty-two patients (59%) achieved improvement of ALP levels after the treatment with UDCA. Those patients (Group A) had significantly lower levels of ALP at diagnosis than those with abnormal ALP levels after 6 months' treatment with UDCA (Group B; P = 0.020). They continued UDCA monotherapy, and maintained normal ALP levels at subsequent follow ups. However, immunoglobulin M (IgM) levels remained abnormal in eight patients, whose IgM levels at the time of diagnosis were significantly higher than those whose IgM were normalized after 6 months' treatment with UDCA (P = 0.026). Those in Group B were treated additionally with bezafibrate, and 12 patients (80%) achieved normal ALP and IgM levels within 12 months of commencement of therapy. CONCLUSION: Higher ALP level at diagnosis is one of the predictors for UDCA failure. Combination treatment of bezafibrate in addition to UDCA may be an effective treatment for PBC patients refractory to UDCA.

Serum cytokeratin 18 M30 antigen level and its correlation with nutritional parameters in middle-aged Japanese males with nonalcoholic fatty liver disease (NAFLD).

Cytokeratin (CK) 18 M30 antigen has been proposed as a diagnostic marker of nonalcoholic fatty liver disease (NAFLD). We studied serum CK18 M30 antigen level and examined the correlations among CK18 and biological data, dietary intake, and plasma fatty acid composition in middle-aged Japanese males with (NAFLD; n=42) and without NAFLD (control; n=35). NAFLD was diagnosed if subjects showed fatty liver on abdominal ultrasonography and their alcohol consumption was <20 g/d. They were also confirmed to have negative serological results for tests of autoimmune liver disease and hepatitis B and C. In the NAFLD group, body mass index, waist circumference, serum M30 antigen, alanine transaminase (ALT), cholinesterase, triacylglycerol, LDL-cholesterol, and HbA1c were significantly higher than in the control group. In the fatty acid analysis of plasma phospholipids, significantly higher dihomo-γ-linolenic acid (DGLA), total saturated fatty acids (SFA), and palmitic/linoleic acid ratio as well as lower arachidonic acid/DGLA ratio were observed in the NAFLD group compared with the control group. In the NAFLD group, M30 antigen was correlated positively with serum ALT, plasma DGLA, dietary SFA, and serum TNF-α as determined by partial correlation analysis controlled for BMI. On the basis of multivariate regression analysis using a stepwise method, M30 antigen was significantly associated with ALT and plasma DGLA. Regarding the determinants of NAFLD as revealed by logistic regression analysis, a high odds ratio was observed for plasma DGLA. In conclusion, members of the NAFLD group showed higher levels of serum CK18 M30 antigen and M30 antigen was strongly associated with serum ALT and plasma DGLA. Abnormal fatty acid metabolism may be a factor that causes aggravation of NAFLD.

Addition of transcatheter arterial chemoembolization decreased local recurrence but had no survival benefit to percutaneous ethanol injection therapy for patients with small hepatocellular carcinoma: A multicenter randomized control study.

To assess the efficacy of the additional treatment of transcatheter arterial chemoembolization (TACE) to percutaneous ethanol injection (PEI) therapy for relatively small hepatocellular carcinomas (HCCs), a multicenter randomized control study (RCT) was performed. We conducted an RCT and follow-up study during the enrollment period from 1997 to 1999. Newly diagnosed patients with one to three HCC tumors measuring from 2 to 4 cm (4 cm maximum) in diameter were enrolled. A total of 30 patients initially underwent a combination TACE-PEI or PEI-alone therapies at eight randomly assigned Japanese hospitals. However, 3 patients withdrew. Of the 27 remaining patients, 13 were treated with the combination TACE-PEI therapy and 14 with PEI therapy alone. The patients were observed over several months [median (interquartile range) 33.2 (24.6) months]. There were no significant differences in the background of the patients between the two groups. Among the patients treated with TACE-PEI, the development of a local residual tumor was of significantly lower occurence, compared to the group receiving PEI alone (7.6 and 42.9%, respectively; P=0.024). However, the mean cancer-free time (absence of local or multiple nodule recurrence) or patient survival time was not significantly different between the two groups [PEI alone vs. TACE-PEI: cancer-free time 16.7 (95% CI 7.3-26.0) vs. 22.9 months (95% CI 12.4-33.4); survival time 57.2 (95% CI 37.2-77.2) vs. 42.4 months (95% CI 29.2-55.6)]. Although the combination of TACE and PEI had significant effects on the local tumor control, no efficacy of the addition of TACE to PEI was noted in the prognosis among patients with relatively small HCC tumors.

Clinical characteristics of drug-induced liver injury in the elderly.

AIM: The average age of Japanese patients with drug-induced liver injury (DILI) is expected to rise as the population ages. The aim of this study was to evaluate the clinical characteristics of DILI in elderly Japanese subjects. METHODS: A total of 142 hospitalized patients with DILI were divided into three groups by age (Group A, < 65 years; Group B, 65-74 years; Group C, >/= 75 years). Patients were examined retrospectively with regard to the number of concomitant drugs, duration of drug intake until onset of DILI, clinical types of DILI, treatment, prognosis, and scores on the diagnostic scale described by Digestive Disease Week, Japan 2004. RESULTS: Patients in Group C used more concomitant drugs (P = 0.0019) compared with patients in Group A. The elderly had a higher frequency of unclear duration of drug intake (P = 0.0020), were more likely to experience cholestatic type DILI (P = 0.033), and underwent more intensive treatment for DILI (P = 0.011). There were fewer cases diagnosed as a "high possibility" of DILI in Group C compared with Group A (P = 0.030) and Group B (P = 0.013). In cases diagnosed as "possible" or "low possibility" of DILI, unclear duration of drug intake was more frequently observed in the elderly (P = 0.0027). CONCLUSION: Elderly patients with DILI show different clinical features than younger patients with DILI. These features should be taken into account in the diagnosis and treatment of DILI in the elderly.

Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes.

OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients. RESULTS: Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 +/- 62 vs. 121 +/- 55 pg/ml, P < 0.001; urinary IL-18 97 +/- 159 vs. 47 +/- 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA(1c) (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary beta-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042). CONCLUSIONS: Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.

Arachidonic acid in mononuclear cells and its clinical significance in HCV cirrhotic patients.

OBJECTIVES: An abnormal fatty acid pattern in patients with advanced liver cirrhosis (LC) has been reported in plasma phospholipids and some other tissues. To elucidate the significance of arachidonic acid deficiency on the clinical pathophysiology of LC and hepatocellular carcinoma (HCC), we analyzed the fatty acid compositions of mononuclear cell phospholipids, plasma alpha-tocopherol, and thiobarbituric acid-reactive substances and serum tumor necrosis factor-alpha (TNF-alpha) in cirrhotic patients infected with the hepatitis C virus with and without HCC. METHODS: Twelve cirrhotic patients without HCC (LC patients) and 11 with HCC (HCC patients) were enrolled. Fatty acids were analyzed with gas chromatography. alpha-Tocopherol and TNF-alpha were analyzed by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Statistical analysis was performed by using the unpaired t test with Welch's correction and Spearman's rank-correlation analysis. RESULTS: Significantly low levels of linoleic, dihomo-gamma-linolenic, arachidonic, and eicosapentaenoic acids from mononuclear cell phospholipids were observed in LC and HCC patients compared with control subjects. Plasma alpha-tocopherol was lower and thiobarbituric acid-reactive substances were higher in HCC patients than in controls. Arachidonic acid molar percentage in mononuclear cell phospholipids correlated significantly with lymphocyte count (r = 0.460, P < 0.05) in the cirrhotic patients and with lymphocyte (r = 0.680, P < 0.01) and platelet (r = 0.763, P < 0.01) counts in all subjects. CONCLUSIONS: These results suggested that arachidonic acid in mononuclear cells may have an important role in the pathophysiology of hepatitis C virus associated with cirrhosis and that nutritional management preventing arachidonic acid deficiency may have some beneficial effects on the progression of LC.