Coffee and non‐alcoholic fatty liver disease: Brewing evidence for hepatoprotection?

Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non‐alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non‐alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti‐inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so‐far limited data supporting such effects will be discussed, and the need for further study is highlighted.     

How should we manage patients with non‐alcoholic fatty liver disease in 2007?

Evidence-based management guidelines for non-alcoholic fatty liver disease (NAFLD) are lacking in the Asia-Pacific region or elsewhere. This review reports the results of a systematic literature search and expert opinions. The Asia-Pacific Working Party on NAFLD (APWP-NAFLD) has generated practical recommendations on management of NAFLD in this region. NAFLD should be suspected when there are metabolic risk factors and/or characteristic changes on hepatic ultrasonography. Diagnosis by ultrasonography, assessment of liver function and complications, exclusion of other liver diseases and screening for metabolic syndrome comprise initial assessment. Liver biopsy should be considered when there is diagnostic uncertainty, for patients at risk of advanced fibrosis, for those enrolled in clinical trials and at laparoscopy for another purpose. Lifestyle measures such as dietary restrictions and increased physical activity (aerobic exercise) should be encouraged, although the best management strategy to achieve this has yet to be defined. Complications of metabolic syndrome should be screened for regularly. Use of statins to treat hypercholesterolemia is safe and recommended; frequent alanine aminotransferase (ALT) monitoring is not required. Obese patients who do not respond to lifestyle measures should be referred to centers specializing in obesity management; consideration should be given to bariatric surgery or gastric ballooning. The role of pharmacotherapy remains investigational and is not recommended for routine clinical practice. Non-alcoholic fatty liver disease should be recognized as part of the metabolic syndrome and managed in a multidisciplinary approach that addresses liver disease in the context of risk factors for diabetes and premature cardiovascular disease. Lifestyle changes are the first line and mainstay of management.     

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

Despite the widespread use of vaccines and antiviral drugs, approximately 350‐400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non‐alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.     

Sarcopenia in patients with non‐alcoholic fatty liver disease: is it a clinically significant entity?

Sarcopenia, described as the loss of muscle mass and/or strength, is gaining importance as it can be increasingly related to many chronic diseases. It is also associated with chronic liver disease, and recently it has been more frequently linked to non‐alcoholic fatty liver disease (NAFLD) in particular. Both sarcopenia and NAFLD are subject to complex and intermingled pathophysiological processes, of which some are in common. Furthermore, it is presently unclear if sarcopenia directly contributes to NAFLD or vice versa. The mechanisms that are involved may include obesity, insulin resistance, vitamin D deficiency, aging, physical inactivity and certain cytokines. Current clinical evidence is subject to an important heterogeneity in methods and definitions, with additionally also a relative overrepresentation of evidence in Asian ethnicities. Nonetheless, all studies so far point towards the same association between sarcopenia and NAFLD, including an association with NAFLD‐severity and NAFLD‐related fibrosis. Since the field is in its infancy, clear definitions and further research are needed to aid to improve understanding of the association between NAFLD and sarcopenia. This can eventually lead to additional potential therapeutic interventions. This review attempts to give an overview of the current published literature that links sarcopenia to NAFLD, followed by a discussion of the presumably involved pathophysiological factors, and ends by discussing current unmet needs.     

Electron microscopic findings in non‐alcoholic fatty liver disease: Is there a difference between hepatosteatosis and steatohepatitis?

Background and Aims: Non‐alcoholic fatty liver disease has long been accepted as benign; however, recent evidence suggests that the disease may progress to cirrhosis and hepatocellular carcinoma, although the natural course of the disease is still unclear. This study was designed to comparatively evaluate electron microscopic features of non‐alcoholic fatty liver (NAFL) and non‐alcoholic steatohepatitis (NASH). Methods: Quantitative and semi‐quantitative ultrastructural evaluations were performed on liver biopsies from 23 patients, 10 with NAFL and 13 with NASH. Results: No statistically significant difference was noted between NAFL and NASH patients in ultrastructural features of hepatocytes including megamitochondria, intramitochondrial crystalline inclusions, mitochondrial matrix granules, foamy cytoplasmic appearance, electron‐lucent and glycogen‐containing nuclear regions, lipofuscin granules, or an increased frequency of vesicles containing electron‐dense material in peribiliary Golgi zone; however, the mitochondrial diameter was significantly higher in the NASH patients. Intercellular distance and microvilli between hepatocytes, collagen and electron‐dense material accumulation in the space of Disse, electron‐dense material accumulation and microvillus density in bile canaliculi did not differ significantly between the groups. Conclusions: Our data show that, although NAFL and NASH can be distinguished by their distinct light microscopic features, ultrastructural characteristics are similar, which suggests that NAFL may also have the potential to progress to fibrosis and cirrhosis like NASH.     

What are the risk factors and settings for non‐alcoholic fatty liver disease in Asia–Pacific?

The risk factors and settings for non-alcoholic fatty liver disease (NAFLD) in Asians are reviewed comprehensively. Based particularly on large community-based studies using ultrasonography, case-control series and prospective longitudinal studies, the prevalence of NAFLD in Asia is between 12% and 24%, depending on age, gender, locality and ethnicity. Further, the prevalence in China and Japan has nearly doubled in the last 10-15 years. A detailed analysis of these data shows that NAFLD risk factors for Asians resemble those in the West for age at presentation, prevalence of type 2 diabetes mellitus (T2DM) and hyperlipidemia. The apparent differences in prevalence of central obesity and overall obesity are related to criteria used to define waist circumference and body mass index (BMI), respectively. The strongest associations are with components of the metabolic syndrome, particularly the combined presence of central obesity and obesity. Non-alcoholic fatty liver disease appears to be associated with long-standing insulin resistance and likely represents the hepatic manifestation of metabolic syndrome. Not surprisingly therefore, Asians with NAFLD are at high risk of developing diabetes and cardiovascular disease. Conversely, metabolic syndrome may precede the diagnosis of NAFLD. The increasing prevalence of obesity, coupled with T2DM, dyslipidemia, hypertension and ultimately metabolic syndrome puts more than half the world's population at risk of developing NAFLD/non-alcoholic steatohepatitis/cirrhosis in the coming decades. Public health initiatives are clearly imperative to halt or reverse the global 'diabesity' pandemic, the underlying basis of NAFLD and metabolic syndrome. In addition, a perspective of NAFLD beyond its hepatic consequences is now warranted; this needs to be considered in relation to management guidelines for affected individuals.     

Decreased immunoexpression of survivin could be a potential marker in human non‐alcoholic fatty liver disease progression?

Background/aim: Regulation of apoptosis in non‐alcoholic fatty liver disease (NAFLD) has been a theme of growing debate. Although no other study assessed the role of survivin in NAFLD, its expression has been reported in hepatic carcinogenesis because of other aetiological factors with relevant discrepancies. The aim of this study was to assess the pattern of survivin immunoexpression by tissue microarray along the whole spectrum of NAFLD, including non‐alcoholic steatohepatitis (NASH)‐related hepatocelular carcinoma (HCC). Methods: Liver biopsies from 56 patients with NAFLD were evaluated: 18 with steatosis, 21 non‐cirrhotic NASH, 10 NASH‐related cirrhosis, seven NASH‐related HCC, as compared with 71 HCC related to other causes and with 12 normal livers. Results: Survivin immunoexpression in NAFLD was restricted to cytoplasm and was found to be progressively lower in advanced stages, including cirrhosis and HCC: steatosis vs NASH‐related cirrhosis (P=0.0243); steatosis vs NASH‐related HCC (P=0.0010); NASH vs NASH‐related cirrhosis (P=0.0318); and NASH vs NASH‐related HCC (P=0.0007), thus suggesting a deregulation of apoptosis from NAFLD towards HCC. Interestingly, survivin immunoreactivity in NASH‐related HCC was also found to be significantly lower than in HCC related to other causes (P<0.05). Remarkably, nuclear staining for survivin was not detected in any case of NAFLD, contrasting to its presence in all other cases of HCC. Conclusions: Survivin immunoexpression in NASH‐related HCC is herein originally found substantially different than in HCC related to other causes, thus requiring further studies to elucidate the role of survivin in human NAFLD progression.     

How common is non‐alcoholic fatty liver disease in the Asia–Pacific region and are there local differences?

Risk factors for development of non-alcoholic steatohepatitis include obesity, especially central adiposity, glucose intolerance or type 2 diabetes mellitus (T2DM), and dyslipidemia. Non-alcoholic fatty liver disease (NAFLD) is now considered a manifestation of metabolic syndrome. During the last two decades, NAFLD has become the most common chronic liver disease in North America and Europe, but until recently was thought to be uncommon (perhaps due to the lack of study) in Asia. Fatty liver can be identified on imaging modalities (ultrasonography, computed tomography scans, and magnetic resonance imaging) with high sensitivity, but steatohepatitis and fibrosis cannot be distinguished. Thus, an inherent drawback in studying the epidemiology of NAFLD is the lack of definitive laboratory tests, no uniform definition-with different studies using cut-off values of alcohol consumption from <20 g/week to 210 g/week, and case selections where biopsy was used for definition. In studies outside the region, the prevalence of NAFLD varies from 16% to 42% by imaging, and 15-39% of liver biopsies. The major risk factors for NAFLD, central obesity, T2DM, dyslipidemia, and metabolic syndrome, are now widely prevalent and are increasing geometrically in the Asia-Pacific region. It is therefore not surprising that NAFLD is common in this region. Estimates of current prevalence range from 5% to 30%, depending on the population studied. Central obesity, diabetes, and metabolic syndrome are the major risk factors. To date, however, data on the natural history and impact of NAFLD causing serious significant chronic liver disease are lacking and there is a need for prospective, cooperative studies.     

Herbal drugs in liver disease: how safe are they?

A 24-year-old man presented with jaundice to our center and further evaluation revealed the presence of acute hepatitis E infection, an infection common in India. The patient's parents consulted a traditional medicine practitioner for giving him native medications for jaundice, a practice very common in India. After taking native medications for 5 days, he developed fulminant liver failure and was readmitted to our center and, in spite of resuscitative and supportive measures, he succumbed to his illness. This clinical situation epitomizes the challenge that we physicians in India face when we confront a patient with liver disease, wherein we have to balance the application of scientific knowledge and the use of native medications by patients. Herbal medicines have been in vogue right from the Vedic period in India at around 600 BC and continue to be used even now for various forms of diseases, particularly affecting the liver. This study aims to highlight this issue and its implications for the treating physicians and the public.     

Beyond obesity: Is cholesterol‐induced liver injury the cause of non‐alcoholic steatohepatitis?

See article in J. Gastroenterol. Hepatol. 2012; 27: 1520-1527.