Contact : mohamed.rela@ildtindia.com

Causes of Liver Disease

Non-alcoholic Fatty Liver Disease

What is it?
This is a chronic condition characterized by accumulation of fat in the liver. It is the commonest cause of abnormal liver function tests in the community and affects 30% of the population around the world. It is much more common in patients with diabetes. In India, due to carbohydrate rich diets, even lean persons have been found to have this problem. Metabolic syndrome comprised of central obesity, diabetes mellitus, hypertension and hyperlipidemia, is closely associated with fatty liver disease.

How does it occur?
NAFLD is characterized by accumulation of fat droplets within liver cells. Long-standing fat accumulation in some patients leads to inflammation in the liver. Presence of fat and inflammation causes liver injury and sets off a process leading to scarring and eventually cirrhosis, where the liver shrinks in size and becomes nodular. It is now believed that many cases of cirrhosis of unknown cause are probably due to NAFLD.

What are the symptoms?
Like most chronic liver conditions, patients with NAFLD are asymptomatic until late in their illness even after progression to cirrhosis. Most patients are rather diagnosed incidentally. Unfortunately, several patients have advanced disease at presentation to us. Jaundice, altered consciousness, fluid accumulation in the abdomen (ascites) and legs, blood vomit and black stools are seen in patients with end stage liver disease. Most patients by this time become malnourished and too weak to perform their day to day activities. In addition, presence of cirrhosis increases the risk of primary liver cancer (hepatocellular carcinoma) by several fold.

How can it be diagnosed early?
The presence of risk factors such as obesity, diabetes, hypertension should increase our suspicion regarding this problem. Blood tests in the early stage of NAFLD may show slightly elevated liver enzymes (AST and ALT) but this condition can exist even with normal liver function tests. Ultrasound abdomen is readily available, is non-invasive and inexpensive. It may show a ‘bright liver’ suggestive of fatty liver. However, it is not a sensitive test until the fat in the liver is moderate to severe and abdominal obesity reduces its accuracy. Fibroscan (Transient elastography) is a new tool that measures liver stiffness. It identifies fibrosis (scarring) and also the progression of fibrosis that occurs as a consequence of NAFLD. It is simple to use, non-invasive, inexpensive and reproducible.

Liver biopsy is the best test for detection and assessing the severity of fatty liver. However, it is an invasive procedure and is not commonly used. A combination of clinical parameters, liver enzymes, and ultrasound are used to diagnose fatty liver disease.

How to treat fatty liver disease?
Life style modification is the most important aspect of treatment for fatty liver disease. This involves weight loss through change in dietary habit and exercise. Weight loss of 5-10% over 6 months has been shown to improve NAFLD and obesity. Too rapid a weight loss by starvation is not recommended as it may worsen the problem.

Diet
High calorie intake significantly contributes in the development of fatty liver disease. Diet rich in carbohydrates and saturated fats should be avoided. Most fast-food and aerated soft drinks increase liver fat, worsen liver injury and should be avoided. Diets rich in fruits & vegetables with limited red meat consumption are recommended.

Exercise
Regular exercise such as brisk walking, jogging or swimming helps weight reduction, improvement in liver enzymes and decreases the risk of diabetes. Moderate exercise with expenditure of at least 400 calories, 3-4 times a week improves NAFLD in the short term.

Medications
A variety of drugs have been used to treat this condition with unimpressive results and sometimes serious side effects. Some new drugs such as Losartan and Exenetide show promise but are still under evaluation. Herbal medications for weight loss are notorious for causing further liver damage and should be avoided.

Bariatric surgery
Bariatric surgery may be considered for morbidly obese (BMI>40) patients who are otherwise unable to lose weight by other measures. Most of these procedures can now be done by key-hole surgeries. However, careful evaluation of the severity and stage of liver disease is necessary as bariatric surgery is contraindicated in patients with advanced liver disease. In such patients, sudden deterioration in liver function can occur.

Liver transplantation is indicated in patients with end stage cirrhosis due to fatty liver disease that develops complications such as liver failure or liver tumors.

Alcoholic Liver Disease

Alcohol is the most common cause of serious liver disease in our country. In addition to the liver, it can also seriously damage the pancreas and heart.

How does alcohol damage the liver?
Alcohol damages the liver by several mechanisms.Patients with alcoholic liver disease go through three phases of liver damage.

1. Simple steatosis (fatty liver): Stopping alcohol at this stage completely reverses the liver damage.

2. Alcoholic hepatitis: This is a serious condition where patients present with severe jaundice, altered consciousness, and sometimes fever. These patients are highly prone for infection. Many patients with alcoholic hepatitis may have underlying cirrhosis. These patients may require ICU care with adequate fluid balance, nutrition and supportive measures. Stopping alcohol at this point is still beneficial in reducing long-term damage.

3. Cirrhosis. Here the patient becomes malnourished and weak. He/she may develop fluid accumulation in the abdominal cavity, may vomit blood leading to liver failure and death. There is also the risk of liver cancer in these patients.

How much can I drink without developing liver disease?
Patients who consume excess alcohol regularly over several years are more likely to develop cirrhosis. Alcohol consumption of over 90 ml of liquor or equivalent quantity of beer or wine will definitely lead to serious liver disease. There is however, no safe level of alcohol consumption below which liver disease cannot develop.Those who binge drink on the weekends are not spared!

Viral Hepatitis

Hepatitis B

The extent of the problem
In India, around 4% of the population carry hepatitis B virus. In some areas in the North-East it can be as high as 12%. According to the WHO nearly 40 million Indians carry hepatitis B virus. It is 100 times more infectious than HIV. It spreads from mother to baby, through needles, blood transfusions and unprotected sex. Hepatitis B virus infection rarely produces symptoms until late in the illness. Therefore, most patients are unaware that they carry the virus. Most patients get detected incidentally, during a master health checkup, prior to blood donation or when one of their family members are diagnosed with hepatitis B. Chronic hepatitis B infection leads to cirrhosis and liver cancer. Worldwide, hepatitis B infection is the commonest cause of primary liver cancer.

Diagnosing Hepatitis B infection
Despite the lack of symptoms the Hepatitis B virus causes ongoing liver injury. However due to the large size of the liver and its ability to repair itself liver functions tests can be normal. Hepatitis B infection can only be diagnosed by a specific blood test. A patient diagnosed with hepatitis B infection, should get evaluated further to know how much virus they carry, how active the virus is and the amount of liver damage. Blood tests such as Liver function tests (LFT), Hepatitis B DNA, Hepatitis B e antigen and antibody status, and abdominal scan help in evaluation. Based on these tests, your hepatologist will make a decision regarding treatment. Not all patients with hepatitis B require treatment, but they certainly require regular follow up because the disease may progress so that treatment may be necessary at a later date and also, to screen for liver cancer.

Treatment of Hepatitis B
Suppression of the virus with treatment limits progression of liver disease to cirrhosis, and prevents development of liver cancer. There are 2 types of treatment available for chronic hepatitis B infection. Pegylated interferon works by stimulating your genes to fight against the virus. The advantage of treatment with Peg-IFN is that the treatment consists of an injection given under the skin on a weekly basis for a year (finite therapy). IFN is more suitable for younger people who need not take long-term tablets, women at the child bearing age, patients with more inflammation and less scarring. Because, interferon does not act on the virus directly it does not cause resistance. Interferon related side effects are flu like symptoms, which usually occurs after the day of injection but settles in 1-2 days. Some patients may develop low white cell count, depression and thyroid problems. For these reasons patients on IFN get monitored every 1-4 weeks. Symptoms improve with subsequent injections. Response to treatment is assessed by means of blood tests.

Oral anti-viral drugs act directly to suppress viral replication. Lamivudine and adefovir are the older drugs. Newer generation drugs are Telbivudine, Entecavir and Tenofovir. The main difference between these two generation of drugs is the development of viral resistance which is extremely rare with newer drugs particularly Entecavir and Tenofovir. These drugs usually need to be taken for years and should not be stopped without your Hepatologist advice. These drugs are well tolerated and side effects are rare.

Do all patients with hepatitis B need treatment?
Patients who are in the inactive carrier phase of the infection need not be treated with antiviral therapy. Your Hepatologist would know the phase of your disease from the blood tests and advise you accordingly. Even if no treatment is given, regular checkups with blood tests and scans is essential as the virus may become active and cause liver damage without any symptoms. This can only be detected by blood tests. Hence all patients with hepatitis B should undergo 6- monthly abdominal ultrasound and a blood test (AFP) to screen for liver cancer.

Hepatitis B vaccination
Universal immunization against hepatitis B is highly effective and is strongly recommended. It is especially necessary when a family member is detected to be hepatitis B positive. All family members of patients with hepatitis B should be screened for the virus. If they are negative, they should be vaccinated to prevent the viral infection.

Hepatitis C

Extent of the problem
Around 1-4% of the Indian population suffers from hepatitis C viral infection. It spreads by transfusion of inadequately screened blood and blood products, cross-infection through dialysis machines, sharing used needles and shaving razors and through unprotected intercourse.

Diagnosis
Like hepatitis B infection, patients will be asymptomatic for decades. Detection is usually made during a master health check up, screening blood donors or family screening. Chronic hepatitis C virus leads to cirrhosis and its dreadful complications including primary liver cancer. Diagnosis is through blood tests and abdominal scan. In addition to determining the stage of your liver disease and the amount of virus, subtype of the virus should be determined.

Treatment
All patients with hepatitis C viral infection should be treated with anti-viral therapy. Treatment consists of Peg-IFN (injection) and ribavirin (tablets) combination therapy. The duration of treatment depends on the subtype (genotype) of the virus. Genotype 1 and 4 requires 48 weeks of therapy, whereas genotype 2 and 3 require 24 weeks of therapy. Response to treatment must be assessed at regular intervals -4 weeks, 12 weeks, at the end of treatment and 3 months after stopping treatment. If the virus remains undetectable at 3 months after completion of treatment, you are cured! In genotype 1 the chance of cure is around 40-60% and for genotype 2 and 3 the cure rate is 70-80%.

Newer drugs known as Directly Acting Anti-Virals(DAAs) like Sofusbuvir and Simeprevir in combination with ribavirin have been extremely effective in clearing the Hepatitis C virus. These medicines are now freely available in the world market, but caution needs to be exercised regarding their use and need to be taken only under the guidance of your Hepatologist. They require shorter treatment duration and the cure rate are as high as 90 to 95%.