1.Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name
Cheng Han NG ; Daniel Q. HUANG ; Mindie H. NGUYEN
Clinical and Molecular Hepatology 2022;28(4):790-801
Nonalcoholic fatty liver disease (NAFLD) affects about a third of the world’s adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a “positive” diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.
2.Diabetes and Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease
Pai-Chi TENG ; Daniel Q. HUANG ; Ting-Yi LIN ; Mazen NOUREDDIN ; Ju Dong YANG
Gut and Liver 2023;17(1):24-33
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.
4.Global incidence and prevalence of nonalcoholic fatty liver disease
Margaret LP TENG ; Cheng Han NG ; Daniel Q. HUANG ; Kai En CHAN ; Darren JH TAN ; Wen Hui LIM ; Ju Dong YANG ; Eunice TAN ; Mark D. MUTHIAH
Clinical and Molecular Hepatology 2023;29(Suppl):S32-S42
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.
5.The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Cheng Han NG ; Kai En CHAN ; Yip Han CHIN ; Rebecca Wenling ZENG ; Pei Chen TSAI ; Wen Hui LIM ; Darren Jun Hao TAN ; Chin Meng KHOO ; Lay Hoon GOH ; Zheng Jye LING ; Anand KULKARNI ; Lung-Yi Loey MAK ; Daniel Q HUANG ; Mark CHAN ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J. SANYAL ; Mark MUTHIAH
Clinical and Molecular Hepatology 2022;28(3):565-574
Background/Aims:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods:
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results:
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
6.Global prevalence of depression and anxiety in patients with hepatocellular carcinoma: Systematic review and meta-analysis
Darren Jun Hao TAN ; Sabrina Xin Zi QUEK ; Jie Ning YONG ; Adithya SURESH ; Kaiser Xuan Ming KOH ; Wen Hui LIM ; Jingxuan QUEK ; Ansel TANG ; Caitlyn TAN ; Benjamin NAH ; Eunice TAN ; Taisei KEITOKU ; Mark D. MUTHIAH ; Nicholas SYN ; Cheng Han NG ; Beom Kyung KIM ; Nobuharu TAMAKI ; Cyrus Su Hui HO ; Rohit LOOMBA ; Daniel Q. HUANG
Clinical and Molecular Hepatology 2022;28(4):864-875
Background/Aims:
Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC.
Methods:
MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model.
Results:
Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC.
Conclusions
One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.