Fatty liver disease—A review with recent updates... Liver Problems

Current Scenario of fatty liver disease in India-

Liver disease is fast spreading like an epidemic in India with one out of every five adults getting affected. Liver-related deaths in India have reached a staggering figure of 268,580 (3.17% of all deaths) per year contributing to 18.3% of global 2 million liver-related deaths.

A recent AIIMS study, which analysed published reports on fatty liver disease in India, states that over one-third (38 per cent) of Indians have fatty liver or non-alcoholic fatty liver disease.

liver problem

What is fatty liver disease?

Fatty liver is when there is too much fat in your liver. The liver is the body’s main organ for processing food and waste materials. A healthy liver contains very little or no fat. If you drink too much alcohol, or eat too much food, your body deals with this excess by turning some of the calories into fat. This fat is then stored in liver cells. When fat makes up more than 5% to 10% of the total weight of your liver, you have fatty liver.

What are the symptoms of fatty liver disease?

Fatty liver disease usually doesn’t cause symptoms. People who have symptoms may have-

• Feeling of tiredness

• Pain in the upper right part of their abdomen

• Loss of weight

Signs in fatty liver disease include-

• yellow eyes and skin (jaundice)

• bruising

• dark urine

• Swollen abdomen

• vomiting blood

• black stools

• itchy skin

What causes fatty liver disease?

Fatty liver is usually due to a combination of factors over a long period of time.

The most common causes of fatty liver are:

• being obese or overweight especially around the abdomen

• having type 2 diabetes mellitus or insulin resistance

• having high blood cholesterol or high triglycerides

• drinking too much alcohol

Less common causes are:

• an underactive thyroid

• certain medicines

• having polycystic ovary syndrome (PCOS)

• Some people can also get fatty liver because of complications that develop late in pregnancy.

What are types of Fatty liver disease

There are 2 main types of fatty liver disease:

1.Metabolic (dysfunction) associated fatty liver disease

2.Alcohol-related fatty liver disease

Metabolic (dysfunction)associated fatty liver disease

Metabolic associated fatty liver disease is the most common type of fatty liver disease. This has also been previously known as:

• non-alcoholic fatty liver disease

• non-alcoholic hepatic steatosis

This type of fatty liver disease is caused by:

• being overweight or obese

• not being active enough

Alcohol-related fatty liver disease

Alcohol-related fatty liver disease is caused by drinking too much alcohol over long periods.

What are the risk factors for development of fatty liver

Major risk factors

• Central adiposity, overweight/obesity, insulin resistance, type 2 diabetes, atherogenic dyslipidaemia, arterial hypertension, metabolic syndrome

• Dietary factors (high-calorie diets rich in saturated fats and cholesterol, soft drinks high in fructose, highly processed foods)

• Sedentary lifestyle/occupation/low level of physical activity

• Sarcopenia

Disease associations

• Cardiovascular disease

• Cerebrovascular disease

• Chronic kidney disease

• Osteoporosis

• Cancer

• Cognitive changes

• Hyperuricemia

• Hypothyroidism

• Polycystic ovarian syndrome

• Hypopituitarism

• Sleep apnoea syndrome

• Polycythaemia

• Gut dysbiosis

All patients with metabolic abnormalities are at risk of MAFLD. Patients should be screened for MAFLD if they have type 2 diabetes, are overweight or obese, or have metabolic risk abnormalities, even if they are lean.

What are the diagnostic modalities available for Fatty Liver

The most widely used detection modality for the presence of steatosis is ultrasonography, which is recommended as the first-line tool for diagnosis.

Ultrasonography is usually sufficient to diagnose the presence of liver fat; however, the sensitivity of ultrasonography is limited when steatosis is <20% of hepatocytes, and performance is suboptimal in individuals with a BMI of >40 kg/m2.

If available, liver stiffness should be measured by elastography as it is a more sensitive tool.

Liver elastography can be used with both ultrasonography and magnetic resonance imaging. Transient elastography with the Fibro Scan device uses pulse-echo ultrasound waves to evaluate liver stiffness as an indirect indicator of the presence or absence of advanced fibrosis and steatosis. It can be used in most patients, except in those with severe obesity. Magnetic resonance elastography is very sensitive at diagnosing steatosis and fibrosis, but it is expensive and not widely available.

Currently there are no robust liquid biomarkers that can confidently and easily be used outside of research settings to diagnose the presence of hepatic steatosis.

Liver biopsy remains the gold standard test for both diagnosis and staging of the disease but is infrequently used.

• Once a diagnosis of MAFLD is made, the next step is to assess the stage of fibrosis, as this is the most important predictor of liver-related morbidity and mortality in patients, with the highest risk among those with cirrhosis Fibrosis staging can be performed by using a combination of non-invasive liver scores (e.g. Fibrosis-4 [FIB-4] and NAFLD Fibrosis Score [NFS] or liver stiffness measurement by elastography. The FIB-4 and NFS can be easily calculated using smartphone apps.

(The Fibrosis-4 score and NFS are non-invasive tools using age, aspartate aminotransferase and alanine aminotransferase values, platelet count, BMI, albumin and diabetes like parameters to identify patients at risk for fibrosis.)

What is the management protocol for Fatty liver disease

Most patients with MAFLD do not require specialist hepatology referral and are best managed holistically in primary care. There is no approved pharmacotherapy for MAFLD. Hence, current management involves reducing the burden of metabolic dysregulation to reduce both liver injury and adverse extrahepatic outcomes.

The cornerstone of current therapy remains lifestyle modification including dietary change, weight loss and structured exercise intervention.

Lifestyle intervention programs focusing on weight loss can reduce liver fat content, with subsequent resolution of steatohepatitis and fibrosis, and improve a patient’s quality of life in a dose-dependent manner.

The overall aim of lifestyle intervention should be a hypocaloric diet (500–1000 kcal deficit) resulting in weight loss (up to 1 kg/week).There is no strong evidence to support a particular dietary approach for the resolution of MAFLD.

In terms of exercise for the resolution of MAFLD, there is no clear consensus on the optimal type, intensity or volume. There appears to be a dose-dependent relationship between exercise volume and reduction in hepatic fat, while exercise has clear benefits for cardiovascular health, which is critical as cardiovascular disease is the leading cause of death for people with MAFLD.

An important strategy is to reduce or remove medications that are steatogenic with long-term use, such as corticosteroids, valproic acid, methotrexate and amiodarone.

These decisions should be made after consideration of each patient’s risk versus benefit profile for their underlying condition, and in discussion with the relevant specialist doctors.

MAFLD is one of many disease entities associated with metabolic dysregulation; others include cardiovascular and renovascular disease. As part of a diagnosis of MAFLD, patients require evaluation for cardiovascular risk, with particular attention to dyslipidaemia, hypertension and diabetes.

Management of these associated entities, and referral to speciality care if required, is part of the essential treatment plan for patients with MAFLD. Currently there are no head-to-head evidence-based treatments for dyslipidaemia, hypertension and type 2 diabetes in the setting of MAFLD.

Disease-specific management

There are no evidence-based medications for the treatment of MAFLD. However, MAFLD is a ‘hot’ area for clinical trials, with >200 ongoing trials in various phases worldwide.

Several of the compounds being investigated have shown promising results in early phase trials, but phase III trial data are awaited. Highly promising are the newer insulin-sensitising agents, such as GLP-1 receptor agonists. Metformin does not improve liver histology.

Bariatric and metabolic therapies (both endoscopic and surgery) can be beneficial for patients with MAFLD, reducing steatosis, inflammation and fibrosis. According to recent systematic reviews and meta-analyses, resolution of hepatic steatosis is seen in >75% of patients following bariatric and metabolic therapies.

The lack of randomised controlled trials to investigate bariatric surgery and other procedures for the treatment of MAFLD currently limits the risk versus benefit evaluation; therefore, bariatric surgery should not be used with MAFLD as the primary indication.

Long-term monitoring

Patients with MAFLD without fibrosis can be monitored at intervals of 2–3 years in the absence of worsening metabolic risk factors using a combination of non-invasive liver scores (e.g. NFS and FIB-4) and liver stiffness measurement by elastography in primary care.

Patients with MAFLD and fibrosis (especially those with stage 2 fibrosis, pre-cirrhosis or cirrhosis) should have the benefit of specialist consultation, which will likely determine the long-term monitoring schedule on the basis of individual patient characteristics.

Patients with cirrhosis should undergo six-monthly surveillance for hepatocellular carcinoma with abdominal ultrasonography and alfa-fetoprotein measurements, and all will require endoscopy at some stage to look for and manage varices, especially patients with a platelet count <150 × 109/L.

FAST FACTS-

• MAFLD is a consequence of metabolic dysregulation resulting in increased fat deposition in the liver.

• MAFLD can develop in lean patients, and patients with metabolic risk factors should be screened.

• Screening for hepatic steatosis should be performed with abdominal ultrasonography; if available, additional assessment with liver elastography and non-invasive liver scores should be considered.

• Management of MAFLD currently focuses on weight loss, an improved dietary composition and increased physical activity.

• There is no current specific pharmacological treatment for MAFLD however many clinical trials are going on worldwide.

****************************************************************

Blog by Dr. Aditi Kumar