IV) NASH Symposium

Symposium (IV)

NASH SYMPOSIUM

UPDATED PREVALENCE OF NAFLD AND NASH IN ASIA

Jian-Gao Fan Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the world, and affects around 25% of adult population. From 2012 to 2017, the global liver-related deaths have increased 11.4% according to the Global Burden of Disease study. The Asia–Pacifc region with over 50% of the world’s population and accounted for 54% of cirrhosis-related deaths and 73% of hepatocellular carcinoma (HCC)-related deaths, respectively. NAFLD is the most rapidly growing contributor to liver mortality and morbidity both in the Western countries and the Eastern countries. The exponential growing burden of NAFLD parallels the increasing prevalence of obesity and type 2 diabetes mellitus in the Asia region. A recent systematic review and meta-analysis of the prevalence, incidence, and outcomes of NAFLD in the Asian population comprising 237 studies (13 044 518 individuals) suggested that the overall prevalence of NAFLD was 29·62% (exceeded that in the West), and up to 25% of NAFLD have developed to nonalcoholic steatohepatitis (NASH). NAFLD prevalence increased significantly over time from 25·28% between 1999 and 2005, through 28·46% between 2006 and 2011, to 33·90% between 2012 and 2017. The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years. The annual incidence of HCC in NAFLD patients was 1·8 cases per 1000 person-years and overall mortality rate was 5·3 deaths per 1000 person-years. Within the Asia–Pacifc region, NAFLD prevalence varies widely as would be predicted from tremendous variations in genetic background, urbanisation, overnutrition, reduced physical activity, and a sedentary lifestyle. However, there is a common trend to increasing prevalence of obesity and NAFLD with time in the entire AsiaPacific region. Asia is a populous region with a quick spread of the childhood obesity epidemic as well. Recently, we did a systematic review with metaanalyses to provide the prevalence of and risk factors for pediatric NAFLD in Asia. Of 33 included Asian populations, 9 studies comprising 20595 children reported a pooled NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), which increased about 1.6-fold from 2004-2010 to the last decade. The pooled prevalence of NAFLD was ranked in increasing order for normal-weight (1.49%; 95% CI 0.88%-2.51%; 2610 participants), overweight (16.72%, n=1265), and obese (50.13%, n=6434) among Asia children. After full covariate adjustment, the multivariate meta-regression showed that boy percentage and body mass index were positively correlated with NAFLD. In this regard, pooled analysis showed that after age 10 years, boys were more prone to have NAFLD than girls. Furthermore, cardio-metabolic risk factors such as waist circumference, systolic and diastolic blood pressure, serum triglycerides, and insulin resistance were significantly associated with NAFLD. In addition, chronic hepatitis B (CHB) and NAFLD are increasingly observed together in Asian populations, and development of NASH represents

another leading cause of liver-related morbidity and mortality. Patients with concomitant NASH and CHB had more incidence of HCC and shorter time to development of liver-related outcomes or death compared to patients with CHB alone. In our newly published multicenter, prospective study including 1000 naïve biopsy-proven CHB patients, 18.2% of whom fulfilled the criteria of NASH at baseline, and 727 patients received the second biopsy at the end of 72-week entecavir treatment. Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up, 46% (63/136) achieved NASH resolution. Patients with baseline BMI ≥ 23 kg/m2 and weight gain were less likely to have NASH resolution. Furthermore, among CHB patients without steatosis at baseline, 7% (35/505) had incident significant steatosis during follow-up, with an incidence of 50.0 per 1000 person-years. Among CHB patients who had no or bland steatosis at baseline, 22 (4%) developed NASH at the end of follow-up, with an incidence as 14.4 per 1000 person years. Baseline BMI ≥ 23 kg/m2 and 1.5% weight gain during follow-up were predictors of incident NASH in CHB patients during antiviral treatment.

Symposium (IV)

NASH SYMPOSIUM

METABOLIC DERANGEMENT AND RESTORATION OF PATIENTS WITH NAFLD

Jee-Fu Huang Hepatitis Centre and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Non-alcoholic fatty liver disease (NAFLD) has been recognized as one of the most common liver disorders globally. It is also on a trajectory to become the most common indication for liver transplantation worldwide. The epidemic has particularly been rapidly progressing in the past decades in AsiaPacific in parallel to the rapid Westernization in the region. The relative lower BMI in Asians is not protective from metabolic insults. Moreover, Asian people are more prone to metabolic syndrome (MetS), type 2 DM (T2DM) and NAFLD than other races. Previous studies from Taiwan clearly demonstrated that the prevalence of NAFLD has been increasing for more than 2 folds within less than 20 years. Therefore, there is a pressing need for elucidation of the clinical characteristics of NAFLD and its management in a practical fashion since the increasing trend of NAFLD epidemic can’t be overlooked in recent decade. Non-alcoholic steatohepatitis (NASH) was defined by histopathologic evidence as an extreme form of NAFLD. NASH has been a histologically defined disease, characterized by hepatic steatosis, ballooning, and lobular inflammation with variable fibrosis. The metabolic liver disorder carries the risk of development of fibrosis, cirrhosis and liver-related deaths. It’s commonly associated with related metabolic diseases, leading to cardiovascular events as its leading cause of death. The metabolic disorders include abdominal obesity, hypertension, dyslipidemia and insulin resistance (IR) and further increase the risk of cardiovascular disease (CVD), T2DM and chronic kidney disease (CKD). The scenario of a higher overall mortality due to CVD as compared with controls has made it a critical global issue. Lifestyle modification consisting of diet, exercise, and weight loss has been advocated to be the initial step for management of NASH patients. The strategies have been widely adopted into the major current guidelines. Among them, weight loss has been reported as the most effective one in improving the histology features and regression of NASH. Several studies have evaluated lifestyle changes, particularly diet and exercise in managing NASH. The adherence of lifestyle modification remains problematic in a large proportion of NASH patients. It is difficult for patients with morbid obesity and musculoskeletal disorders to do sufficient exercise. Besides, the efficacy of lifestyle modification could not be applied to those lean NASH patients. In addition, the available clinical trials typically apply extensive exclusion criteria and have limited generalizability. Therefore, pharmacological treatment may be required in some patients. Currently, there is no effective drug approved for therapeutic indication for NAFLD/NASH. With multiple agents and/or compounds currently recruited into phase 2 to 3 clinical trials, it is important to consider how the eventual approval of a pharmacologic agent for NASH will impact ongoing and future clinical trials in this aspect.

Symposium (IV)

NASH SYMPOSIUM

CURRENT AND FUTURE THERAPEUTIC APPROACHES FOR PATIENTS WITH NASH

Ching-Sheng Hsu Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the world and highly linked to metabolic syndrome. Current management for NAFLD/NASH should not only target liver-related outcomes but also modulate risk factors of cardiovascular diseases and diabetes progression. Therefore, a holistic approach including liver-directed treatments, lifestyle intervention, body weight control, and correction of metabolic derangements are needed to prevent or delay liver diseases progression and minimize the risks of the development of cirrhosis-related complications, cardiovascular diseases, chronic renal diseases, tissue damage caused by metabolic derangements, infection, and malignancy. To optimize the current management for NAFLD/NASH, a variety of potential targets playing essential roles in the pathogenesis of NAFLD/ NASH have been identified and served to develop novel agents for the treatment of NAFLD/NASH. In today’s talk, we will review some important data regarding the current therapeutic approaches and the emerging novel agents for the treatment of NASH and NAFLD.

Symposium (IV)

NASH SYMPOSIUM

NON INVASIVE DIAGNOSIS OF NAFLD/NASH

Laurent Castera Department of Hepatology, Hôpital Beaujon, Clichy, France

There are two key issues in NAFLD patients: the differentiation of NASH from simple steatosis and the identification of advanced hepatic fibrosis that drives overall and liver-related mortality. Given the epidemic proportion of individuals with NAFLD worldwide, liver biopsy, is impractical and has been challenged over the past decade by non-invasive methods. These methods rely on two distinct but complementary approaches: a “biological” approach, based on the quantification of biomarkers of fibrosis in serum, and a “physical” approach, based on the measurement of liver stiffness using either elastography- or magnetic resonance-based elastography. None of the currently available non-invasive methods can differentiate NASH from simple steatosis. As for the identification of advanced fibrosis, simple and inexpensive serum biomarkers such as FIB-4 or the NAFLD fibrosis score may be used as firstline tools to rule-out advanced fibrosis, given their high negative value (>90%). TE as the most widely available and validated technique worldwide could be used as second line in referral centers to select patients with suspected advanced fibrosis for liver biopsy. As for magnetic resonance elastography, although it appears as the most accurate noninvasive technique for staging fibrosis, given its high cost and limited availability, it remains a tool for research or clinical trials. Updated EASL clinical practice guidelines on non-invasive tests have been published in 2021 and will be presented.