Impact of the New Definition of Metabolic Associated Fatty Liver Disease on the Epidemiology of the Disease.

BACKGROUND & AIMS: Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. We aimed to study the impact of the new definition on the epidemiology of fatty liver disease. METHODS: We randomly selected 1013 adults from the Hong Kong census database for clinical assessment, proton-magnetic resonance spectroscopy, and transient elastography. Five hundred sixty-five subjects without fatty liver at baseline underwent follow-up assessment. MAFLD was diagnosed as intrahepatic triglyceride content (IHTG) ≥5% and the presence of overweight/obesity, diabetes, or two other metabolic risk factors, with and without concomitant liver diseases. The diagnosis of NAFLD required the exclusion of concomitant liver diseases; metabolic factors were not considered. RESULTS: The population prevalence of MAFLD and NAFLD was 25.9% (95% CI 23.2-28.7%) and 25.7% (95% CI 23.1-28.5%), respectively. Among 277 subjects with IHTG ≥5%, 247 (89.2%) fulfilled both the definitions of MAFLD and NAFLD. Fourteen subjects (5.1%) had IHTG ≥5% but did not meet the metabolic criteria of MAFLD. The incidence of MAFLD was 2.8 per 100 person-years at a median interval of 47 months (range 34-60 months). Among 78 subjects with incident NAFLD, 59 (75.6%) met the criteria of MAFLD; only one of the latter, a regular drinker, had liver stiffness ≥10 kPa. CONCLUSIONS: The new definition of MAFLD does not significantly change the prevalence compared with NAFLD, but it may reduce the incidence by 25%. People with hepatic steatosis but not fulfilling the definition of MAFLD unlikely have significant liver disease.

Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study.

BACKGROUND AND AIMS: Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. APPROACH AND RESULTS: We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow-up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow-up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m. CONCLUSIONS: The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes.

Repeating measurements by transient elastography in non-alcoholic fatty liver disease patients with high liver stiffness.

BACKGROUND AND AIM: The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false-positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy. METHODS: Ninety-seven patients with non-alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut-off of 7.9 kPa was used to exclude F3-4 fibrosis. RESULTS: Seventy-eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3-4. Nineteen patients had low LSM at baseline; none of them had F3-4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3-4, the negative predictive value remained high at 91%. The positive predictive value for F3-4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut-offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3-4. CONCLUSIONS: Transient elastography is a highly sensitive screening test to exclude F3-4 fibrosis in non-alcoholic fatty liver disease patients. One-third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy.

Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response. METHODS: A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m2 was used to define non-obese NAFLD. RESULTS: Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m2, respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group. CONCLUSIONS: Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population. LAY SUMMARY: Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.