The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease
The main cause of liver diseases worldwide is metabolic associated fatty liver disease (MAFLD) and affects nearly a quarter of the global population. Mohammed Eslam and colleagues published guidelines for advancing clinical practices under the title “The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease” in the Hepatology International journal. Th summary of the guidelines are given below:
Objective:
To recommend the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD.
Method:
The guideline was developed from the currently available evidence along with the scientific and medical knowledge by experienced clinicians and researchers.
Recommendations:
Recommendations for etiology of fatty liver disease
• Metabolic associated fatty liver disease – type 2 diabetes mellitus, Overweight/obese, metabolically unhealthy normal-weight individuals
• Alcohol associated fatty liver disease – Significant alcohol consumption (>21 standard drinks per week in men and>14 standard drinks per week in women over a 2-year period), binge drinking (>5 standard drinks in men and>4 standard drinks in women over a 2- h period), and lifetime alcohol intake>100 kg
• Alternative causes of fatty liver disease – Long-term use of steatogenic medications (corticosteroids, valproic acid, tamoxifen, methotrexate, amiodarone, etc.), exposure to some chemicals, HCV genotype 3 infections, Wilson’s disease, coeliac disease, starvation, total parenteral nutrition, severe surgical weight loss, disorders of lipid metabolism (abetalipoproteinemia, hypobeta lipoproteinemia, lysosomal acid lipase deficiency, familial combined hyperlipidemia, lipodystrophy and Mauriac syndrome), Weber–Christian syndrome, glycogen storage disease, Cushing’s syndrome, etc
Recommendation for Risk factors for MAFLD
• Major risk factor- Overweight/obesity, Central obesity, Type 2 diabetes mellitus, Dyslipidemia, Arterial hypertension, Metabolic syndrome, Insulin resistance, Dietary factors: high-calorie diets rich in saturated fats and cholesterol, soft drinks high in fructose, highly processed foods, Sedentary lifestyle or sedentary occupation, low level of physical activity, Sarcopenia
• Common and uncommon risk factor – Gut microbiota, Hyperuricemia, Hypothyroidism, Sleep apnoea syndrome, Polycystic ovary syndrome, Polycythaemia, Hypopituitarism; Genetic variations: PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13; Epigenetic factors: microRNAs (miR), DNA methylation, histone modification, and ubiquitination alterations; A personal or family history of T2DM, premature vascular disease, atherogenic dyslipidemia and high blood pressure (metabolic syndrome), fatty liver.
Recommendations for considering MAFLD with other liver diseases
• MAFLD can and many times does coexist with other liver diseases (A1).
• MAFLD treatment and that of accompanying diseases should be as per the recommendations for each of the diseases (B1).
Recommendation for screening of high‑risk population for MAFLD
• Screening for MAFLD by ultrasonography should be considered in at-risk populations such as patients with T2DM, overweight/obesity, and metabolic syndrome (A1).
• Patients with MAFLD should be identified for other components of metabolic syndrome and be treated accordingly (A1).
• Advice and support for lifestyle interventions should be given to patients with MAFLD to reduce the risk of events from metabolic and cardiovascular disease, and to resolve fatty liver disease (A1).
Recommendation for managing the extra‑hepatic manifestations of MAFLD
• MAFLD patients should be evaluated for cardiovascular disease and cardiovascular risk, and referred to a cardiologist, in case it is necessary (A1).
• Hypertension, dyslipidemia, and diabetes mellitus should be assessed and treated accordingly to reduce the risk of cardiovascular and kidney disease (A1).
Recommendation for using non‑invasive scores in MAFLD
• Abdominal ultrasonography is suggested as a first-line diagnostic modality for imaging of MAFLD and is usually sufficient for the detection of hepatic steatosis (A1).
• If available, vibration-controlled transient elastography (VCTE) may be used to measure controlled attenuation parameters (CAP) as a more sensitive tool than ultrasonography. If imaging methods are not available or feasible such as epidemiological studies with a large number of subjects, serum biomarkers and scores such as the fatty liver index (FLI) may be considered as an alternative method for the diagnosis of steatosis (B2).
• Magnetic resonance imaging-based techniques such as proton-MRS and MRI-PDFF are considered the gold standard to quantify liver fat but it is not recommended useful tool for routine clinical practice in early phase clinical trials (A1).
• There is no strong biomarker for steatohepatitis and liver biopsy is the only test of choice for assessment of steatohepatitis (A1).
• The removal of the high risk of significant or advanced fibrosis is acceptable using liver stiffness measurement by VCTE or shear wave elastography, non-invasive tools, and blood biomarkers and scores of fibrosis or their sequential combination (A2).
• There is less accuracy in confirmation of significant or advanced fibrosis by liver stiffness measurement and/or serum biomarkers or scores and would require further confirmation by liver biopsy as per the clinical context (B2).
Recommendations: Indications for liver biopsy in patients with suspected MAFLD (A1)
• Uncertain diagnosis and evaluation for dual causes.
• Non-invasive tests suggesting indeterminate or nonconcordant results.
• During cholecystectomy and bariatric surgery.
• Approved research
Recommendation for pathological reporting
• A standardized reporting of histological lesions in MAFLD patients is necessary for the enrolment in clinical trials, the study of natural history, and evaluation of response to treatment and comparison of data within different geographic locations (A1).
• Histological evaluation should include at least eosin stains and hematoxylin, and either picrosirius red stain or Masson’s trichrome stain (A1).
• Reporting should be standardized for histological lesions in MAFLD using either the FLIP algorithm and SAF score or the NASH CRN system for reporting (B1).
Recommendation for diagnosis of MAFLD‑cirrhosis
Patients with cirrhosis in the absence of typical histology should be considered as having MAFLD-related cirrhosis if they meet the following criteria:
Past or present evidence of metabolic risk factors as per the criteria to diagnose MAFLD, with at least one of the following:
• Documentation of MAFLD on a prior liver biopsy.
• Historical documentation of steatosis using hepatic imaging (B2).
History of past alcohol intake should be considered as patients may have dual disease cause along with alcohol use disorder
Practical recommendations for lifestyle intervention in MAFLD
• Lifestyle change to adopt a healthy diet and physical activity norms via structured programmes are
recommended for MAFLD (C2).
• Patients without steatohepatitis or fibrosis should be counseled for a healthy diet and physical activity without pharmacotherapy for their liver disease (B2)
• Weight loss is beneficial for both overweight/obese and nonobese MAFLD. In the former, a 7–10% weight loss is the aim of most lifestyle interventions and results in the improvement of liver enzymes and histology (B1).
• Dietary recommendations should include energy restriction and exclusion of MAFLD-mediating components. A Mediterranean-type diet is advisable (B1).
• Combined diet/exercise strategies are more effective in reducing liver fat, normalization of liver enzyme levels, and improving histology (B1).
• Both aerobic exercise and resistance training effectively reduce liver fat and should be individualized as per patient preferences to ensure long-term adherence. Resistance exercise may be more feasible as compare to aerobic exercise for MAFLD patients with poor fitness (B2).
Recommendations for bariatric (metabolic) surgery in MAFLD
• Histological lesions of MAFLD, including fibrosis are improved by bariatric surgery along with the reduction in liver fat (B1).
• the decision should be individualized because of the high risk of post-operative complications from bariatric (metabolic) surgery in patients with cirrhosis (C1).
Recommendations for monitoring the progress of treatment in MAFLD
• Patients without fibrosis can be observed at intervals of 2 or 3 years in the absence of worsening of metabolic risk factors with the help of a combination of non-invasive scores and liver stiffness measurement (C2).
• Patients with fibrosis should be monitored on yearly basis using a combination of non-invasive scores and liver stiffness measurement (C2).
• Patients with cirrhosis should be monitored at 6-month intervals along with surveillance for hepatocellular carcinoma (A2).
• In a subgroup of patients who are at high risk of fibrosis progression, monitoring may include a repeated liver biopsy every 5 years’ follow-up, unless they have established cirrhosis (C2).
Recommendation for the role of patient reported outcomes in MAFLD
• Patient views on satisfaction, quality of life, and compliance are essential to developing a patient-centered approach to impact MAFLD outcomes (B2).
• Patients with MAFLD appear to have worse physical, mental, HRQoL, and fatigue scores compared to patients with other causes of chronic liver disease such as hepatitis B and C (B2).
Recommendation for management of special groups (non‑obese and pediatric) with MAFLD
• Lifestyle intervention with regular exercise gives positive outcome in treating MAFLD and in improving overall fitness and metabolic co-morbidities irrespective of baseline BMI (B1).
• for pediatric MAFLD, Lifestyle change is the only prevention and treatment strategy though beneficial effects on fibrosis are yet to be demonstrated. There is no effective and safe drug treatment approved for fibrosis in pediatric MAFLD(B1).
Recommendation for management of MAFLD‑HCC
• Control of obesity and diabetes could be beneficial in MAFLD-related HCC patients (B1).
• Metformin might be a beneficial treatment in MAFLD related HCC patients with T2DM (C2).
• Serum albumin level is a prognostic factor and nutritional therapy concentrating on protein metabolism is important for the management of patients with MAFLD-related HCC (C2).
Recommendations for liver transplantation in MAFLD
• Post-transplant survival for MAFLD patients is equivalent to that of other liver diseases in appropriately selected patients. Liver transplantation should be considered for MAFLD patients with decompensated liver disease or hepatocellular carcinoma (B1).
• Patients with MAFLD cirrhosis have a high prevalence of pre-existing cardiovascular disease and should be thoroughly assessed before listing for transplantation (B1).
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