Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Our previous studies found that the activation of insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II (ANG II)-induced cardiomyocyte apoptosis. However, the detailed mechanism by which ANG II regulates IGF-IIR in heart cells remains elusive. In this study, we found that ANG II activated its downstream kinase JNK to increase IGF-IIR expression through the ANG II receptor angiotensin type 1 receptor. JNK activation subsequently led to sirtuin 1 (SIRT1) degradation via the proteasome, thus preventing SIRT1 from deacetylating heat-shock transcription factor 1 (HSF1). The resulting increase in the acetylation of HSF1 impaired its ability to bind to the IGF-IIR promoter region (nt À 748 to À 585). HSF1 protected cardiomyocytes by acting as a repressor of IGF-IIR gene expression, and ANG II diminished this HSF1-mediated repression through enhanced acetylation, thus activating the IGF-IIR apoptosis pathway. Taken together, these results suggest that HSF1 represses IGF-IIR gene expression to protect cardiomyocytes. ANG II activates JNK to degrade SIRT1, resulting in HSF1 acetylation, which induces IGF-IIR expression and eventually results in cardiac hypertrophy and apoptosis. HSF1 could be a valuable target for developing treatments for cardiac diseases in hypertensive patients. Apoptosis has been implicated in a wide variety of cardiovascular disorders, including myocardial infarction and heart failure, suggesting that activation of apoptotic pathways contributes to cardiomyocyte loss and subsequently cardiac dysfunction. Previous studies reported that several extracellular molecules, such as insulin-like growth factors (IGFs) and angiotensin II (ANG II), are involved in the development of cardiac hypertrophy and apoptosis.

Background: Overweight and hepatic steatosis have been increasingly recognized recently. This study aimed to test whether substantial amount of fatty infiltration in liver, which may interfere with cytoplasmic distribution of hepatitis B surface antigen (HBsAg), can contribute to HBsAg seroclearance in HBsAg carriers. Methods: Clinical and laboratory data including ultrasound grading of hepatic steatosis were studied in 54 HBsAg carriers with HBsAg seroclearance, and the results were compared with 108 age-and sex-matched carriers with HBsAg persistence. Results: Body mass index and ultrasound grading of hepatic steatosis were significantly higher in HBsAg carriers with HBsAg seroclearance than in those with HBsAg persistence. The degrees of hepatic steatosis correlated significantly with body mass index (Po0.001). The prevalence of mild hepatic steatosis showed no significant difference (33% (18/54) vs 31% (33/108), P ¼ 0.72), but moderate-severe hepatic steatosis was significantly more prevalent in patients with HBsAg seroclearance (33% (18/54) vs 13% (17/108), P ¼ 0.01). HBsAg carriers with moderate and severe hepatic steatosis were associated with a 3.2-fold (95% confidence interval: 1.2-8.4, P ¼ 0.02) and 3.9-fold (95% confidence interval: 1.1-14.2, P ¼ 0.04), respectively, increased odds of HBsAg seroclearance compared to those without hepatic steatosis. Conclusion: Moderate-severe hepatic steatosis may contribute to HBsAg seroclearance in HBsAg carriers.

SUMMARYTo elucidate the long‐term results of percutaneous ethanol injection (PEI) for hepatocellular carcinoma (HCC), 47 cirrhotic patients with HCC ≤5 cm after PEI were analysed. Thirty‐two of the patients were male. The age range was 37‐68 years. Thirty‐nine patients were seropositive either for hepatitis B surface antigen or antihepatitis C virus antibody. There were a total of 61 tumours, including solitary tumours in 35 patients, double tumours in 10 and triple tumours in two. The size of the main tumour was ≤3 cm in 29 patients and more than 3 cm in 18 patients. Seventeen, 27 and three patients were in Child's class A, B and C respectively; 5‐10 ml 95% ethanol was injected into the tumour every three to seven days until the echogenicity of the tumour changed to a hyperechoic or heterogeneous one. A booster PEI was given in 34 (56%) lesions with viable tumour, which was detected by dynamic computed tomography. The one, two, three and and four‐year survival rates were 85%, 75%, 61% and 39% respectively for all patients. Good liver reserve significantly improved the survival rate (p<0.01, Child's class A and B vs Child's class C). The one, two, three and four‐year recurrence rates were 24%, 55%, 69% and 79% for all patients. HCC recurred more frequently in patients with multiple tumours (p<0.02).

Fifteen patients with HBsAg-positive, severe chronic active hepatitis, nine DNA polymerase (DNAP)-positive and six negative were treated with intravenous adenine arabinoside (Ara-A) in a dose of 10 mg/kg/day for five consecutive days during each of two consecutive weeks. Of the DNAP-positive patients, two responded with histological and clinical remission as well as permanent loss of DNAP. However, histological and clinical remission were also observed in patients with unsatisfactory DNAP response and even in DNAP-negative patients. It is suggested that, in addition to its antiviral effect, Ara-A might have another mechanism, such as immunosuppression, that induced histological and clinical remission. Alternatively, the discrepancy of response might relate to the natural course of chronic type B hepatitis. Accordingly, controlled trial is mandatory for assessing the effect of Ara-A or any other agent in the treatment of chronic type B hepatitis.