Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

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.

Background/Aims: Due to increases in obesity and type 2 diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has also been increasing. Current forecast models may not include non-obese NAFLD. Here, we used the Bayesian approach to forecast the prevalence of NAFLD through the year 2040. Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were performed for age, gender, presence of metabolic syndrome, region, and smoking status. Sensitivity analysis was conducted for clinical setting and study quality. Results: The forecasted 2040 prevalence was 55.7%, a three-fold increase since 1990 and a 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years, the 2040 prevalence were not significantly different (56.7% vs. 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males: 60% vs. 50%) but the trend was steeper for females (annual percentage change: 2.5% vs. 1.5%, P=0.025). There was no difference in trends overtime by region (P=0.48). The increase rate was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or study quality (P=0.85). Conclusion By 2040, over half the adult population is forecasted to have NAFLD. The largest increases are expected to occur in women, smokers, and those without metabolic syndrome. Intensified efforts are needed to raise awareness of NAFLD and to determine long-term solutions addressing the driving factors of the disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.
Biomarkers/analysis ; Chenodeoxycholic Acid/analogs & derivatives/therapeutic use ; Clinical Trials as Topic ; Fatty Liver/diagnosis ; Fibrosis ; Humans ; Liver/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Non-alcoholic Fatty Liver Disease/*diagnosis/drug therapy ; Tomography, X-Ray Computed ; Ultrasonography ; Vitamin E/therapeutic use

Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. Methods: Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995–2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). Results: The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5–3.5% and 4.3–7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022).Conclusions: Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.

BACKGROUND/AIMS: A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. METHODS: The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. RESULTS: Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], –0.30; 95% confidence interval [CI], –0.57 to –0.03) but not hepatic steatosis in RCT (SMD, –0.1; 95% CI, –0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, –3.0; 95% CI, –6.9 to 0.91). CONCLUSIONS Ezetimibe decreased NAS without improving hepatic steatosis.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). Conclusions People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.