Hepatology Research

Non‐alcoholic fatty liver disease (NAFLD) is a major public health problem both in the Western world and in the East. This is mainly due to the high prevalence of the disease and its effects on the individual with NAFLD. In the USA, it is estimated that approximately a third of the general population has NAFLD. Increasing age, obesity and the presence of multiple features of metabolic syndrome, especially diabetes, are associated with a higher probability of having non‐alcoholic steatohepatitis (NASH). In the individual with NAFLD, excess hepatic fat is associated with an increased risk of developing diabetes, hypertension, cardiovascular events, abnormal resting electrocardiography and endothelial dysfunction. These findings have been corroborated in studies in teenagers as well as adults. There is also an increase in cardiovascular mortality, especially in those with NASH. In addition, there is an increased risk of death from a variety of non‐hepatocellular cancers. From a liver perspective, NAFLD is associated with a 15–20% risk of progression to cirrhosis. The disease progresses more rapidly in those with diabetes, increasing age and obesity. The PNPLA3 gene mutation at position 148 is associated with not only steatosis, but with the likelihood of having steatohepatitis and increased inflammation and fibrosis. Once cirrhosis develops, the liver disease decompensates at the rate of 3–4% per year. NASH‐related cirrhosis is a risk factor for hepatocellular cancer. All of these factors indicate that NAFLD is a common condition that has significant adverse health consequences for those who are afflicted. It is therefore a major public health hazard throughout the world

Mục tiêu:  Statin, một chất ức chế 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, được báo cáo có ích trong việc điều trị viêm gan nhiễm mỡ không do rượu (NASH). Hiện nay, chưa có liệu pháp đã được chứng minh cho NASH. Trong nghiên cứu này, chúng tôi đã đánh giá hiệu quả của rosuvastatin ở bệnh nhân NASH có rối loạn lipid máu.

Phương pháp:  Mười chín bệnh nhân có chẩn đoán sinh thiết NASH và rối loạn lipid máu đã đồng ý tham gia nghiên cứu tiến triển này được chọn lựa. Các bệnh nhân đã được điều trị trong 24 tháng với liều 2.5 mg/ngày rosuvastatin. Những thay đổi lâm sàng và mô học được đánh giá so sánh trước và sau điều trị. Hướng dẫn giảm cân tiêu chuẩn được tiếp tục trong thời gian điều trị. Sinh thiết gan theo dõi được thực hiện trên chín bệnh nhân.

Kết quả:  Hai mươi sáu phần trăm bệnh nhân mắc rối loạn lipid máu loại IIa và 74% mắc rối loạn lipid máu loại IIb tại thời điểm ban đầu. Chỉ số khối cơ thể trung bình không thay đổi đáng kể trong quá trình điều trị. Mức độ transaminase tương đối thấp từ đầu và không thay đổi đáng kể trong cả quá trình điều trị. Hồ sơ lipid cải thiện đáng kể sau 24 tháng điều trị với rosuvastatin. Trong khi điểm hoạt tính bệnh gan nhiễm mỡ không do rượu và giai đoạn xơ hóa không thay đổi đáng kể ở tất cả bệnh nhân, tỷ lệ cải thiện đạt 33,3% ở bệnh nhân cá nhân và duy trì ổn định ở 33,3% và 55,6% tương ứng.

Kết luận:  Các tham số chuyển hóa liên quan đến NASH cải thiện với liệu pháp bao gồm cả mô học ở một số bệnh nhân. Tuy nhiên, một trong số chín bệnh nhân có tình trạng xơ hóa tiến triển trong suốt quá trình điều trị. Nghiên cứu thí điểm của chúng tôi cho thấy hiệu quả của rosuvastatin trong điều trị NASH kèm rối loạn lipid máu, ngay cả khi transaminase không tăng cao và thử nghiệm kiểm soát cần thiết trong tương lai.

Alcoholic liver disease (ALD) has become one of the most critical health problems in many countries, including Japan. Liver injury in ALD ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular carcinoma. Many factors are thought to contribute to the development and progression of ALD, particularly insulin resistance, generation of reactive oxygen species during alcohol metabolism, adipokines from visceral adipose tissue, and endotoxin derived from the gut. Although the pathogenesis of ALD has been widely investigated, the precise mechanisms are yet to be elucidated and many questions remain. This article reviews the possible mechanisms for the development of ALD identified to date.

Aim:  Non‐alcoholic fatty liver disease (NAFLD) that encompasses a spectrum of liver disorders characterized by simple steatosis, non‐alcoholic steatohepatitis (NASH) through cirrhosis, is becoming an important chronic liver disease in Japan. Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of statin therapy in NASH patients with dyslipidemia.

Methods:  Twenty patients with biopsy‐proven NASH with dyslipidemia who agreed to participate in this multicentric prospective study were enrolled. The patients were treated for 12 months with pitavastatin 2 mg/day. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight loss counseling was continued during the treatment period. Follow‐up liver biopsy was performed in 13 patients.

Results:  Twenty‐five percent of patients had hyperlipoproteinemia type IIa and 75% had hyperlipoproteinemia type IIb at baseline. The levels of alanine aminotransferase, γ‐glutamyl transpeptidase and lipid profiles were significantly improved by the treatment with pitavastatin for 12 months. Especially, these improvements were prominent in NASH patients with hyperlipoproteinemia type IIb. While non‐alcoholic fatty liver disease activity score and fibrosis stage did not change significantly in all patients, they did improve in 54% and 42% in individual patients, respectively.

Conclusion:  NASH‐related metabolic parameters improved with therapy including histology in some patients. However, three of 13 patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of pitavastatin for the treatment of NASH with dyslipidemia, especially with hyperlipoproteinemia type IIb and controlled trials are needed in the future.

Aim:  Carnosic acid (CA) inhibits adipogenesis in vitro. The present study evaluated the therapeutic effects of CA in ob/ob mice.

Methods:  The experimental animals were given a standard chow diet with or without CA for 5 weeks. Bodyweight gain and food intake were measured during this period. Magnetic resonance imaging analysis, histological examination, serum chemistry analysis and intraperitoneal glucose tolerance test (IPGTT) were all performed.

Results:  The mice fed CA experienced significant weight loss and reduced visceral adiposity, in addition to significantly reduced serum triglyceride (TG) and cholesterol levels. Importantly, CA had a dramatic effect on the liver by reducing the hepatic TG content, thus decreasing serum alanine aminotransferase levels. In addition, IPGTT revealed that CA significantly improved glucose tolerance.

Conclusion:  These data suggest that CA is a novel therapeutic agent for obesity‐related non‐alcoholic fatty liver disease.