What Is Non-Alcoholic Steatohepatitis (NASH)?
The severe form of (NAFLD) non-alcoholic fatty liver disease is known as NASH (non-alcoholic steatohepatitis). Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of liver disease which holds:
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Simple infiltration (steatosis).
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Fat and inflammation (non-alcoholic steatohepatitis - NASH).
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Liver cirrhosis, in the absence of excessive alcohol consumption.
NASH damages and inflames the liver, leading to scarring of the liver (cirrhosis). It is linked with progressive liver fibrosis, which is a life-threatening condition.
What Are the Stages of NASH?
The three different stages of NASH are,
Stage 1 -Stage 1 is called compensated cirrhosis and NASH without fibrosis. The word compensated cirrhosis is termed because the liver is compromised in this stage, but it continues to function normally. The liver is slightly larger, with inflammation and fat more than 5 % (steatosis).
Stage 2 -Stage 2 is referred to as NASH with fibrosis, where in addition to the features of stage 1, scarring (fibrosis) of the liver occurs. Fibrosis involves four stages, but stage 2 consists of fibrosis 1 to fibrosis 3.
Stage 3 -Stage 3 of NASH is the severe stage where cirrhosis of the liver occurs (whole liver) or liver cancer. This stage could be treated only with a liver transplant. Damage to the liver by NASH is dangerous for the cardiovascular system as it releases free radicals into the bloodstream.
Who Are at High Risks of NASH?
The events in NASH are based on the development of,
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Obesity.
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Insulin resistance and type 2 diabetes mellitus (non-insulin-dependent) leading to increased hepatic free fatty acid flux.
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Hypertension.
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Dyslipidemia.
Excessive sitting during a day with little physical exercise and having unhealthy dietary patterns increase the prevalence of obesity and insulin resistance, leading to liver dysfunction.
The other considered risk elements are,
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Poor diet.
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Polycystic ovarian disease (PCOD).
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High cholesterol.
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Small bowel bacterial overgrowth.
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High triglyceride.
NASH can also be a hereditary cause, and the family members with NASH or NAFLD are at more risk. A two-hit hypothesis has been proposed to describe the pathogenesis where the first hit causes the steatosis that then progresses to steatohepatitis.
NASH is caused by the combination of:
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Oxidative stress - Due to free radicals produced during fatty acid oxidation.
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Tumor necrosis factor-alpha (cytokine release).
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Immune factors.
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Direct lipotoxicity.
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Gut-derived endotoxin.
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Endoplasmic reticulum stress.
NASH was associated with a greater than tenfold increased risk of liver-related death and a doubling of cardiovascular risk over a mean follow-up of 13.7 years.
What Are the Clinical Symptoms of NASH?
The average age of NASH patients is 40 to 50 years. In 50 to 60 years, NASH- cirrhosis occurs (absence of alcohol consumption). Childhood obesity is an emerging epidemic which indicates NASH is present more in younger patients. NASH is frequently asymptomatic at the early stages, and so it is called a silent disease, although it may be associated with:
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Fatigue.
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Mild right upper abdomen discomfort.
NASH presents late in the natural history of the disease with complications of cirrhosis and portal hypertension, such as variceal hemorrhage.
NASH leads to cirrhosis of the liver leading to symptoms like:
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Confusion.
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Itchy skin.
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Weakness.
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Bleed easily.
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Loss of appetite.
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Jaundice (late stages).
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Anorexia.
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Bruising.
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Nausea and vomiting.
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Drowsiness
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Abdominal discomfort.
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Slurred speech.
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Swelling in the legs.
How Can We Diagnose NASH?
NASH cannot be ruled out early, at the same time it can only be identified with a physical examination and by analyzing the complete medical history. It can be confirmed by blood tests where there are no single diagnostic blood tests.
Blood Tests:
Elevations of serum alanine transaminase and aspartate aminotransferase are frequently elevated, whereas a rise in the serum bilirubin may occur later. Alanine transaminase levels fall as hepatic fibrosis increases, and the characteristic alanine transaminase and aspartate aminotransferase ratio of less than one is seen in NASH. NASH reverses as the disease progresses towards cirrhosis, meaning that steatohepatitis with advanced disease may be present even in those with normal range alanine transaminase levels.
Ultrasound:
Ultrasound is most often used and provides a qualitative assessment of hepatic fat content, as the liver appears bright due to increased echogenicity. But sensitivity is limited when fewer than 33 % of hepatocytes are steatotic. Alternatives that offer greater sensitivity for detecting lesser degrees of steatosis include:
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CT (computed tomography).
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MRI (magnetic resonance imaging).
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MR spectroscopy.
Liver Biopsy:
It is the standard test for the diagnosis and assessment of the degree of inflammation and extent of liver fibrosis.
The microscopic definition of NASH is based on a combination of three lesions:
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Hepatocellular injury.
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Inflammation.
The biopsy shows hepatocyte ballooning degeneration with or without spotty necrosis and a mild, mixed inflammatory infiltrate. Perisinusoidal fibrosis is considered to be an important feature of NASH. Histological scoring systems evaluate the severity of disease semi-quantitatively. Hepatic fat content diminishes as cirrhosis evolves, hence NASH is under-diagnosed in the setting of advanced liver disease. It is called cryptogenic cirrhosis, as the underlying etiology of 30 % to 75 % of cases is not known.
How Is NASH Managed?
In recognition of the greater morbidity associated with NASH, liver-targeted treatment should be focused particularly on those patients with NASH.
Non-Pharmacological Treatment:
Current treatment comprises lifestyle interventions to promote weight loss and improve insulin sensitivity through dietary changes and physical exercise. Sustained weight reduction of 7 % to 10 % is associated with significant improvement in health. In addition, weight loss surgery is also the best option to reduce a tremendous amount of weight.
NASH can be reversed by following the below:
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Reducing cholesterol levels.
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Controlling diabetes.
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Yoga, meditation, and exercise regularly.
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Stopping alcohol consumption.
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Having a healthy weight, researchers say that reducing 10 % of the weight makes a huge difference.
Pharmacological Treatment:
No pharmacological agents are currently licensed specifically for NASH therapy. Treatment directed at coexisting metabolic disorders such as dyslipidemia and hypertension should be given. Specific insulin-sensitizing agents, in particular glitazones, may help selected patients, while positive results with high-dose Vitamin E (800 U/day) have been shown, and the high dose may be associated with an increased risk of prostate cancer.
Conclusion:
Patients with NASH or liver disorders should undergo appropriate treatment at the early stages to avoid painful complications. There are no standard treatments for NASH, therefore with the help of lifestyle modifications, losing weight, having a balanced diet, or with immediate attention to early diagnosis of hypothyroidism and diabetes is important. Avoiding the consumption of excessive alcohol also helps. Eat healthier to live a long life.
