Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Patients with nonalcoholic steatohepatitis (NASH), a severe form of NAFLD characterized by ballooning, lobular inflammation and liver fibrosis, have increased mortality rate and risk of cardiovascular disease. Besides, some patients progress to cirrhosis and may even develop hepatocellular carcinoma. In long-term studies, up to 13% of NAFLD patients died of hepatic complications.(1)
Owing to westernization of lifestyle, NAFLD is also increasing dramatically in Asia. In a population screening study in Shanghai using ultrasonography, 15% of adult Chinese was found to suffer from NAFLD.(2) Among Chinese patients with NAFLD, significant necroinflammation and liver fibrosis are not uncommon.(3-5) These patients also often have progression of liver fibrosis with time.(6)
Since NASH is closely related to type 2 diabetes and obesity, a logical approach would be to improve these metabolic parameters.(7, 8) Observational studies suggest that regular exercise and weight reduction benefit NASH patients. At present, there is no registered drug for the treatment of NASH. Although insulin sensitizers such as pioglitazone and rosiglitazone may improve the metabolic profile and hepatic necroinflammation,(9, 10) the effects are not durable.(11) Weight gain and cardiovascular complications also limit the use of these agents.(12, 13) More effective and better tolerated treatment is urgently needed.
Phyllanthus urinaria (Hepaguard®) is commonly used by patients with various chronic liver diseases.(14-16) Phyllanthus has excellent safety profile. In in vitro and in vivo models of NAFLD, Phyllanthus reduces hepatic steatosis, necroinflammation and fibrosis.(16) Oxidative stress and lipid accumulation are ameliorated. Whether the same beneficial effects apply to humans is unclear.
References:
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2. Fan JG, Zhu J, Li XJ, Chen L, Li L, Dai F, Li F, Chen SY. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol 2005;43:508-14.
3. Wong VW, Chan HL, Hui AY, Chan KF, Liew CT, Chan FK, Sung JJ. Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese. Aliment Pharmacol Ther 2004;20:45-9.
4. Wong VW, Wong GL, Chim AM, Tse AM, Tsang SW, Hui AY, Choi PC, Chan AW, So WY, Chan FK, Sung JJ, Chan HL. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am J Gastroenterol 2008;103:1682-8.
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13. Juurlink DN, Gomes T, Lipscombe LL, Austin PC, Hux JE, Mamdani MM. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ 2009;339:b2942.
14. Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med 1995;126:350-2.
15. Chan HL, Sung JJ, Fong WF, Chim AM, Yung PP, Hui AY, Fung KP, Leung PC. Double-blinded placebo-controlled study of Phyllanthus urinaris for the treatment of chronic hepatitis B. Aliment Pharmacol Ther 2003;18:339-45.
16. Shen B, Yu J, Wang S, Chu ES, Wong VW, Zhou X, Lin G, Sung JJ, Chan HL. Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo. Hepatology 2008;47:473-83.
