肝硬変のサルコペニア

肝硬変のサルコペニアに関するレビュー論文を紹介します。

Srinivasan Dasarath. Consilience in sarcopenia of cirrhosis. Journal of Cachexia, Sarcopenia and Muscle doi:10.1007/s13539-012-0069-3

下記のHPで全文見ることができます。

http://www.springerlink.com/content/hl817166753u1216/fulltext.html

ここでのサルコペニアは広義のサルコペニア（ミオペニア）の意味で使用されています。肝硬変では運動療法の有効性が以下のレビューで示されています。

肝硬変患者の運動能力と筋力
http://rehabnutrition.blogspot.jp/2011/12/blog-post_10.html

しかしこの論文では、運動によって門脈圧が上昇して消化管の静脈瘤出血をおこすリスクがあるので、他のサルコペニアの原因疾患のようには安全ではないかもしれないとしています。その部分の英文だけ引用します。

The role of aerobic and resistance exercise on skeletal muscle insulin signaling, protein synthesis response, AMP kinase activity, and satellite cell function has been identified [50, 135]. However, fatigue, reduced maximum exercise capacity in cirrhotics, and the presence of complications including ascites, encephalopathy, and portal pressure have limited the translation of the data or the elegant designs of the studies performed in noncirrhotic patients [136–143]. Resistance exercise increases portal hypertension, and even transient increases in portal hypertension can result in catastrophic variceal bleeding and death [144]. It is therefore critical that the data on the impact of exercise on muscle mass and function be translated very judiciously in cirrhotic patients.

ただし、肝硬変でも運動療法は有効というエビデンスもすでにあります。そのため、栄養状態、栄養管理、全身状態を考慮しつつ、これらで禁忌とならない場合には、低負荷の有酸素運動とレジスタンストレーニングは行うべきだと私は考えています。

Abstract

Cirrhosis is the consequence of progression of many forms of necro-inflammatory disorders of the liver with hepatic fibrosis, hepatocellular dysfunction, and vascular remodeling. Reversing the primary hepatic disorder, liver transplantation, and controlling the complications are the major management goals. Since the former options are not available to the majority of cirrhotics, treating complications remains the mainstay of therapy. Sarcopenia and/or cachexia is the most common complication and adversely affects survival, quality of life, development of other complications of cirrhosis, and outcome after liver transplantation. With the increase in number of cirrhotic patients with hepatitis C and nonalcoholic fatty liver disease, the number of patients waiting for a liver transplantation is likely to continue to increase above the currently estimated 72.3/100,000 population. One of the critical clinical questions is to determine if we can treat sarcopenia of cirrhosis without transplantation. No effective therapies exist to treat sarcopenia because the mechanism(s) of sarcopenia in cirrhosis is as yet unknown. The reasons for this include the predominantly descriptive studies to date and the advances in our understanding of skeletal muscle biology and molecular regulation of atrophy and hypertrophy not being translated into the clinical practice of hepatology. Satellite cell biology, muscle autophagy and apoptosis, and molecular signaling abnormalities in the skeletal muscle of cirrhotics are also not known. Aging of the cirrhotic and transplanted population, use of mTOR inhibitors, and the lack of definitive outcome measures to define sarcopenia and cachexia in this population add to the difficulty in increasing our understanding of hepatic sarcopenia/cachexia and developing treatment options. Recent data on the role of myostatin, AMP kinase, impaired mTOR signaling resulting in anabolic resistance in animal models, and the rapidly developing field of nutriceuticals as signaling molecules need to be evaluated in human cirrhotics. Finally, the benefits of exercise reported in other disease states with sarcopenia may not be safe in cirrhotics due to the risk of gastrointestinal variceal bleeding due to an increase in portal pressure. This article focuses on the problems facing both muscle biologists and hepatologists in developing a comprehensive approach to sarcopenia in cirrhosis.