Presence of Fatty Liver increases risk of Covid19 complications:
In this observational study, a history of NAFLD/NASH was associated with a significantly increased odds of hospitalization
https://www.medrxiv.org/content/10.1101/2020.09.01.20185850v1
Pathology, Diagnosis and Epidemiology:
NAFLD: Non Alcoholic Fatty Liver Disease is an umbrella diagnosis which includes a spectrum of clinical stages ranging from simple fatty liver to cirrhosis and liver failure.
Due to the strong association with obesity, insulin resistance or type 2 diabetes mellitus, and dyslipidaemia, NAFLD has been described as the hepatic manifestation of the metabolic syndrome
Most patients with nonalcoholic fatty liver disease (NAFLD) are
asymptomatic. However, if questioned, more than 50% of patients with
fatty liver or nonalcoholic steatohepatitis (NASH) report persistent
fatigue, malaise, or upper abdominal discomfort.
Around one third of the population had evidence of steatosis on imaging,
- 70%–90% having simple steatosis
- 10%–30% of subjects with NAFLD have non-alcoholic steatohepatitis (NASH)
NAFL:
Simple fatty infiltration of the liver or hepatic steatosis (fat content
exceeds 5% of liver volume)
Fatty liver is the accumulation of triglycerides and other fats in the liver cells. The amount of fatty acid in the liver depends on the balance between the processes of delivery and removal.
As the condition progresses, fatty liver may be accompanied by hepatic inflammation and liver cell death (steatohepatitis).
NASH:
- fat and inflammation with hepatocyte injury (ballooning) with or without fibrosis
- the risk of progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma is higher
In the USA steatosis affects approximately 25%-35% of the general population. Nonalcoholic fatty liver disease (NAFLD) is found in over 80% of patients who are obese. Asian studies reported NASH and NAFLD occurring at a lower body mass index (BMI). Abnormal glucose tolerance testing is an independent risk factor for progression of nonalcoholic steatohepatitis (NASH)
Average age of people with NASH is 40-50 years and for NASH-cirrhosis 50-60 years. Fibrosis or cirrhosis of the liver is present in 15%-50% of patients with NASH. Approximately 30% of patients with fibrosis develop cirrhosis after 10 years.
Fatty liver accounts for
-Most common cause for liver transplant in women
-Second most common cause for liver transplant in men ( after alcoholic liver disease )
-Third most common cause of Liver Cancer after Alcoholic Liver Cirrhosis and Chronic Hepatitis C
-However the most common causes of death in patients with Fatty liver are
1. Cardiovascular disease such as heart attack and stroke
2. Cancers related to obesity and metabolic syndrome
3. Liver failure.
In about 1/3 of cases of NASH, non-organ specific autoantibodies are found the presence of anti-nuclear antibodies is reported to be associated with more severe insulin resistance and more advanced liver disease
Serum leptin, a cytokine-type peptide hormone mainly produced by adipocytes, may play an important role in the pathogenesis of steatosis. Steatosis occurs with decreased leptin action, whether due to leptin deficiency or resistance.
Data from animal studies and clinical studies support the role of proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) in the early stages of fatty liver, as well as in alcoholic steatohepatitis
Management Strategies:
Management of NAFLD should include treating the associated obesity, hyperlipidemia, insulin resistance, and type 2 diabetes.
Diet & Exercise:
- a calorie restricted diet (600 Kcal less than a person needs to remain at the same weight) should be recommended aiming to lose 0.5–1 kg per week until the target weight is achieved
- patients should avoid saturated fats, simple carbohydrates and sweetened drinks.
- increase physical activity and exercise have been shown to reduce steatosis and improve liver enzyme levels independent of weight loss
- reduce and minimize alcohol intake
A low-fat diet is recommended, and a weight loss goal of 1-2 pounds per week is suggested. Diets associated with improvement include those restricted in rapidly absorbed carbohydrates and those with a high protein-to-calorie ratio
Mounting evidence indicates that high-fructose diets (eg, sodas and preserved foods) are factors for developing fatty liver and that their elimination may reverse fatty liver. The mechanism appears to be related to depletion of adenosine triphosphate (ATP), as well as to increased uric acid production from excess fructose.
In mouse models of NASH, a high-fat diet combined with a high-fructose diet (equivalent to the typical American “fast food diet”) resulted in more liver damage than a high-fat diet alone. In a study of rats on a high-fructose diet, exercise (swimming 1 hour a day, 5 days a week) prevented the development of fatty liver disease.
Multiple human studies have shown that exercise added to diet appears to improve the results and increase insulin sensitivity by increasing muscle mass. Exercise that includes both cardiovascular fitness and weight training should improve NASH. Cardiovascular fitness often results in weight loss. Weight training will increase the muscle mass and improve insulin sensitivity. Combining these two activities helps relieve the underlying derangements of NASH.
Even regular exercise that is not associated with weight loss has been shown to improve fatty liver disease. Most experts agree that walking for 20 minutes 5-7 days a week can stabilize liver disease.
In a randomized trial, improvement on liver biopsy was seen after a 7% weight loss resulting from lifestyle changes (improved diet, exercise, and behavioral modification).Weight loss of 3%-5% of body weight generally reduces hepatic steatosis, but up to 10% weight loss may be needed to improve necroinflammation.
Medical Management:
A study by Foster et al found that Atorvastatin 20 mg, combined with vitamins C and E, is effective in reducing the odds of having hepatic steatosis by 71% in healthy individuals with NAFLD after 4 years of active therapy. It should be noted that Vitamin E supplementation in higher doses has been implicated in possibly being related to Prostate Cancer.
Omega-3 fatty acids may be considered for hypertriglyceridemia in patients with NAFLD
Drugs used for type 2 diabetes which assist weight loss such as GLP1 Agonists ( eg Semaglutide / Ozempic), SGLT2 inhibitors ( eg Empaglifozin / Jardiance ) and Biguanide Metformin / Glucophage are likely to slow progression of fatty liver.
Pioglitazone may be used to treat steatohepatitis in both patients with and without type 2 diabetes with biopsy-proven NASH although this is not usually first line when treating type 2 diabetes and causes weight gain.
Other drugs which have been studied with some early positive results include Ezetimibe, Gemfibrozil and Ursodiol.
Supplements which may help include Black Coffee, Green Tea, Curcumin and Milk Thistle.
Bariatic Surgery is a possible treatment to reduce the burden of NASH in patients who meet the agreed criteria for the management of obesity (BMI >=40 or BMI >=35 with comorbidities)
Therapies
under study currently include NAC ( N- Acetyl Cysteine ) and CPAP for
patients with co-combitant Obstructive Sleep Apnoea.
INFORMATION & DISCLAIMER:
I obtained my primary medical education from India and post graduate MD in Family Medicine from the United Kingdom. After working in National Health Service, England for 15 years, I moved to Canada five years ago. As a Family Physician, I consider my speciality as engaging patients, interpreting medical information for them, guiding them through their health journey, promoting wise health choices and encouraging early detection and management of disease.
The information on this blog is accurate as per time of publishing. Scientific information and evidence changes dynamically and my opinions would change accordingly.
Patient confidentiality must be upheld at all times and any patients wishing to discuss specific medical scenarios on social media are requested to do so anonymously in 'third party' sense.
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