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NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized public health problem, affecting up to a quarter of the world's adult population. The burden of NAFLD is influenced by the epidemics of obesity and type 2 diabetes mellitus (T2DM) and the prevalence of these conditions is not expected to decrease in the forthcoming decades. Consequently, the burden of NAFLDrelated liver complications (non-alcoholic steatohepatitis [NASH], cirrhosis and hepatocellular carcinoma) and the need for life-saving liver transplantation are also expected to increase further in the near future. It is predicted that NAFLD will soon become the most important indication for liver transplantation. A large body of clinical evidence indicates that NAFLD is associated not only with increased liver-related morbidity and mortality, but also with an increased risk of developing other important extra-hepatic diseases, such as cardiovascular disease (that is the predominant cause of death in patients with NAFLD), extra-hepatic cancers (mainly colorectal cancers), T2DM and chronic kidney disease. Thus, NAFLD creates a considerable health and economic burden worldwide and often results in poor quality of life. This narrative review provides an overview of the current literature on main complications, morbidity and mortality of this common and burdensome liver disease.

Aims: To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. Data synthesis: We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62e16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40 e30.28] vs. 11.06% [95% CI 9.73e12.39]), and in patients aged 60 years vs. those aged <60 years (23.30% [95% CI 19.65e26.94] vs. 8.79% [95% CI 7.56e10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n Z 22 studies; random-effects odds ratio 2.10, 95% CI 1.71e2.57; I 2 Z 41.5%) and~threefold increased risk of in-hospital mortality (n Z 15 studies; random-effects odds ratio 2.68, 95% CI 2.09e3.44; I 2 Z 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. Conclusions: Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.

This largest and most updated meta-analysis to date shows that NAFLD (detected by biochemistry, fatty liver index or ultrasonography) is associated with a nearly 40% increase in the long-term risk of incident CKD. However, the observational nature of the eligible studies does not allow for proving causality. Our findings pave the way for future large, prospective, histologically-based studies.

Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.

Risk of severe illness from COVID-19 in patients with metabolic dysfunctionassociated fatty liver disease and increased fibrosis scores A recent study reported that patients with severe COVID-19 were more likely to have non-alcoholic fatty liver disease (NAFLD) compared with those with non-severe COVID-19 illness. 1 However, the prognosis of NAFLD (recently renamed metabolic dysfunction-associated fatty liver disease (MAFLD) 2) is determined by the severity of liver fibrosis. 3 4 We therefore postulated that patients with MAFLD with increased noninvasive liver fibrosis scores are at higher risk of severe illness from COVID-19. We studied 310 patients with laboratoryconfirmed COVID-19 who were consecutively hospitalised at four sites in Zhejiang Province, China, between January and February 2020. Some of these patients (n=150) have been included in a prior study examining the association between obesity and COVID-19 severity. 5 Patients with viral hepatitis, excessive alcohol consumption, chronic pulmonary diseases or active cancers were excluded. Clinical and laboratory data were collected at hospital admission. All patients were screened for hepatic steatosis by computed tomography and subsequently diagnosed as MAFLD. 6 The originally validated cut-points for fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) were used to categorise liver fibrosis probability as low, intermediate or high. 7 COVID-19 severity was classified as severe and non-severe. 8 The study protocol was approved by the local ethics committees of the four hospitals. In our cohort of 310 confirmed cases of COVID-19, 94 (30.3%) patients had MAFLD. As shown in table 1, patients with MAFLD with intermediate or high FIB-4 scores were more likely to be older, obese, have diabetes and have higher NFS, higher liver enzymes, higher C reactive protein, as well as lower levels of lymphocyte count, platelet count, triglycerides and high-density lipoprotein cholesterol compared with their counterparts with low FIB-4 score or those without MAFLD. Notably, the severity

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