Hepatology & Acute Liver Failure

COMMON LIVER DISEASES

Although liver disease is stereotypically linked to alcohol or drugs, the truth is that there are over 100 known forms of liver disease caused by a variety of factors and affecting everyone from children to adults. The most common are infections such as hepatitis A, B, C, D, E, alcohol related, fatty liver, cirrhosis, cancer and drug damage. Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile. There are also many pediatric liver diseases including progressive familial intrahepatic cholestasis, alpha-1 antitrypsin deficiency, alagille syndrome, biliary atresia and langerhans cell histiocytosis. Cirrhosis is often considered to be a form of liver disease and may be the only liver-related condition that many people have heard of. In fact, cirrhosis is a condition that results from permanent damage or scarring of the liver. It is the end stage of many different forms of liver disease and is known to cause a number of other health problems, including variceal bleeding, ascites and hepatic encephalopathy.

Leading Causes For Liver Disease

Many types of liver disease still have unknown causes but the most frequent liver diseases are generally caused by one of the following factors:

Viral Hepatitis

Caused by viruses that attack the liver, viral hepatitis comes in many forms. The most common forms world-wide are hepatitis A, B and C. Although hepatitis A and B can be prevented by vaccine, there is no vaccine for hepatitis C. In India, hepatitis C is the leading cause of liver transplants.

Obesity

The leading cause of liver disease in Indian cities is fatty liver disease linked to obesity.

Alcohol

Factors such as gender, age, geographical location, weight and health can affect how a person’s liver metabolizes alcohol. When the liver has too much alcohol to handle, normal liver function may be interrupted leading to a chemical imbalance. If the liver is required to detoxify alcohol continuously, liver cells may be destroyed or altered resulting in fat deposits (fatty liver) and more seriously, either inflammation (alcoholic hepatitis) and/or permanent scarring (cirrhosis). Liver cancer can also result from alcohol induced liver disease.

Autoimmune Disorders

Sometimes a body’s immune system may begin to attack the liver or bile ducts causing inflammation and scarring which leads to a progressive form of liver disease. Examples of liver diseases believed to be caused by the immune system are primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) andautoimmune hepatitis.

Drugs and Toxins

The liver is responsible for processing most of the chemicals and medications that enter your body – this leaves it vulnerable to acute or chronic liver disease caused by chemicals. In some cases, this is a predictable consequence of overexposure or over-consumption of certain chemicals such as acetaminophen or industrial toxins like polyvinyl chloride or carbon tetrachloride. In other cases, chemicals can cause an unpredictable reaction.

Cancer

Although primary liver cancer is relatively uncommon, many other forms of cancer often metastasize in the liver. Because the liver filters a high volume of blood which may be carrying cancer cells, it is susceptible to developing a form of secondary cancer. If cancer originates in the liver, it is often caused by hepatitis B, hepatitis C or it can develop in cases of advanced liver disease when cirrhosis is present.

Genetics

Several forms of liver disease are caused or thought to be caused, by defective genes. These forms of liver disease may be diagnosed in infancy or may not show up until later in life. Examples include hemochromatosis, Wilson disease, alpha 1 antitrypsin deficiency and Glycogen Storage disease.

FATTY LIVER

Some fat in your liver is normal. But if it makes up more than 5%-10% of the organ's weight, you may have fatty liver disease. If you're a drinker, stop. That's one of the key causes of the condition.

There are two main types of fatty liver disease:

• Alcoholic liver disease (ALD)
• Non-alcoholic fatty liver disease (NAFLD)

You can also get fatty liver disease during pregnancy.

Causes:

Alcoholic Liver Disease (ALD)

You can get alcoholic liver disease from drinking lots of alcohol. It can even show up after a short period of heavy drinking. Genes that are passed down from your parents may also play a role in ALD. They can affect the chances that you become an alcoholic. And they can also have an impact on the way your body breaks down the alcohol you drink. Other things that may affect your chance of getting ALD are:

• Hepatitis C (which can lead to inflammation in your liver)
• Too much iron in your body
• Being obese

Non-alcoholic Fatty Liver Disease (NAFLD)

It's not clear what causes this type of fatty liver disease. It tends to run in families. It's also more likely to happen to those who are middle-aged and overweight or obese. People like that often have high cholesterol and diabetes as well.

Acute Fatty Liver of Pregnancy

It's rare, but fat can build up in your liver when you're pregnant. This could be risky for both you and your baby. It could lead to liver or failure in either of you. It might also cause a serious infection or bleeding.
No one fully understands why fatty liver happens during pregnancy, but hormones may play a role.
Once you get a diagnosis, it's important that your baby gets delivered as soon as possible. Although you may need intensive care for several days, your liver often returns to normal in a few weeks.

Symptoms of Fatty Liver Disease

You might have fatty liver disease and not realize it. There are often no symptoms at first. As time goes on, often years or even decades, you can get problems related to chronic liver disease like:

• Feeling tired
• Loss of weight or appetite
• Weakness
• Nausea
• Confusion, poor judgment, or trouble concentrating

You might have some other symptoms, too. Your liver may get larger. You could have a pain in the center or right upper part of your belly. If you have alcoholic liver disease, you may notice that the symptoms get worse after a period of heavy drinking.

Prevention/treatment of Fatty Liver Disease

There is no specific treatment. But you can improve your condition by managing your diabetes, if you have it.
If you have alcoholic liver disease and you are a heavy drinker, quitting is the most important thing you can do. Talk to your doctor about how to get help. If you don't stop you could get complications like alcoholic hepatitis or cirrhosis. Even if you have non-alcoholic fatty liver disease, it can help to avoid drinking. If you are overweight or obese, do what you can to gradually lose weight -- no more than 1 or 2 pounds a week.
Eat a balanced and healthy diet and get regular exercise. Limit high-carb foods such as bread, grits, rice, potatoes, and corn. And cut down on drinks with lots of sugar like sports drinks and juice.

JAUNDICE

Someone with jaundice is likely to have a yellow look to their skin and the whites of the eyes. Jaundice is caused by a build-up of bilirubin in the blood and body tissue. That build-up is often due to conditions affecting the liver, such as cirrhosis, hepatitis or gallstones.

Symptoms of jaundice

• As well as the classic yellow tinge to the skin and whites of the eyes, someone with jaundice may also have yellowing of mucous membranes in the mouth and nose.
• Stools can be pale in colour and urine dark in colour.
• Some underlying conditions, which lead to jaundice, may feel like flu, and may also result in fever, chills, stomach pain, itching or weight-loss or be without an explanation such as a diet.

Causes of jaundice

When red blood cells break down naturally in a 120-day cycle, bilirubin is produced as a waste by-product. The journey bilirubin takes out of the body's waste disposal systems sees it carried by blood to the liver. There is it combined with bile (digestive fluid) from the gallbladder. This mixture exits the body through faeces and urine. If everything is working well, faeces should be brown and urine light yellow. Infections or damage can disrupt this process, leading to jaundice.

Pre-hepatic jaundice

If an infection or medical condition makes the red blood cells break down sooner than usual, bilirubin levels rise. This is known as pre-hepatic jaundice. Conditions that may trigger this include malaria, sickle cell anaemia, thalassaemia, Gilbert's syndrome, hereditary spherocytosis and Crigler-Najjar syndrome.

Intra-hepatic jaundice

If the liver is damaged, it may be less able to process bilirubin. This causes what doctors call intra-hepatic jaundice. The liver damage may be a result of causes that include hepatitis, alcoholic liver disease, glandular fever, liver cancer, illegal drug use including ecstasy, and paracetamol overdose. Obesity and non-alcoholic fatty liver disease can be a cause of cirrhosis of the liver and jaundice.

Post-hepatic jaundice

Gallstones, pancreatitis, pancreatic cancer and cancers of the gallbladder or bile duct may also disrupt the bilirubin removal process leading to jaundice. This is called post-hepatic jaundice. Eating a high-fat diet can raise your cholesterol levels and increase the risk of having gallstones.

Jaundice diagnosis

The yellowing of skin and eyes are likely to be the main clues a doctor will use before confirming a jaundice diagnosis. A person will be asked about other symptoms and risks, such as foreign travel or drug misuse. A physical examination will be carried out to look for signs of swelling of the liver and legs, ankles or feet, which might indicate cirrhosis of the liver. Urine can be tested for urobilinogen, which is produced when bilirubin is broken down. Finding high or low levels can help pinpoint the type of jaundice. Blood tests may be used to check for conditions like malaria or hepatitis. A liver function blood test may indicate hepatitis, cirrhosis or alcoholic liver disease. Sometimes a liver biopsy - removal of small tissue sample - is needed to confirm or rule out conditions such as cirrhosis or liver cancer. Doctors may also need to look inside the body for problems with the liver or bile duct using ultrasound, X-ray with contrast, MRI or CT scans.

Jaundice treatment

The treatment given to someone with jaundice will depend on what type they have, how serious it is and what caused it. It may include tackling an underlying condition such as malaria and bothersome symptoms, such as itching. For genetic conditions that don't get better, like sickle cell anaemia, a blood transfusion may be given to replenish red blood cells in the body. If the bile duct system is blocked, an operation may be needed to unblock it. During these procedures measures may be taken to help prevent further problems, such as removal of the gallbladder. If the liver is found to be seriously damaged, a transplant may be an option.

Preventing jaundice

As many things can cause jaundice, it is hard for doctors to give specific prevention advice in all cases. General tips include avoiding hepatitis infection, staying within recommended alcohol limits, maintaining healthy weight and managing cholesterol.

NASH

Nonalcoholic steatohepatitis (NASH) is a condition that causes inflammation and accumulation of fat and fibrous (scar) tissue in the liver. Liver enzyme levels in the blood may be more elevated than the mild elevations seen with nonalcoholic fatty liver (NAFL). Although a similar condition can occur in people who abuse alcohol, NASH occurs in those who drink little to no alcohol. The exact cause of NASH is unknown. However, it is seen more frequently in people with certain medical conditions such as diabetes, obesity, hyperlipidemia and insulin resistance. This combination of disorders if often called the metabolic syndrome. People with NASH should be vaccinated against hepatitis A and B if they are not already immune.

Nonalcoholic steatohepatitis symptoms - Most people with NASH have no symptoms. Rarely, NASH is diagnosed in people with fatigue, a general feeling of being unwell, and a vague discomfort in their upper right abdomen, although it is not clear if these symptoms are related to NASH.

Nonalcoholic steatohepatitis diagnosis - NASH is most often discovered during routine laboratory testing. Additional tests help confirm the presence of NASH and rule out other types of liver disease. Imaging tests (such as ultrasound, CT scan, or magnetic resonance imaging [MRI]) may reveal fat accumulation in the liver but cannot differentiate NASH from other causes of liver disease that have a similar appearance. A liver biopsy may be required to confirm NASH if other causes of liver disease cannot be excluded.

Nonalcoholic steatohepatitis treatment:

• Weight loss
• Treatment of insulin resistance
• Vitamin E supplements (only if recommended by your doctor)
• Timely medication

CIRRHOSIS OF LIVER

Cirrhosis is a slowly progressing disease in which healthy liver tissue is replaced with scar tissue, eventually preventing the liver from functioning properly. The scar tissue blocks the flow of blood through the liver and slows the processing of nutrients, hormones, drugs, and naturally produced toxins. It also slows the production of proteins and other substances made by the liver. According to the National Institutes of Health, cirrhosis is the 12th leading cause of death by disease.

What Causes Cirrhosis of the Liver?

Hepatitis C, fatty liver, and alcohol abuse are the most common causes of cirrhosis of the liver in the U.S., but anything that damages the liver can cause cirrhosis, including:

• Fatty liver associated with obesity and diabetes.
• Chronic viral infections of the liver (hepatitis types B, C, and D; hepatitis D is extremely rare).
• Blockage of the bile duct, which carries bile formed in the liver to the intestines, where it helps in the digestion of fats; in babies, this can be caused by biliary atresia in which bile ducts are absent or damaged, causing bile to back up in the liver. In adults, bile ducts may become inflamed, blocked, or scarred, due to another liver disease called primary biliary cirrhosis.
• Repeated bouts of heart failure with fluid backing up into the liver.
• Certain inherited diseases such as:
  • Cystic fibrosis
  • Glycogen storage diseases, in which the body is unable to process glycogen, a form of sugar that is converted to glucose and serves as a source of energy for the body
  • Alpha 1 antitrypsin deficiency, an absence of a specific enzyme in the liver
  • Diseases caused by abnormal liver function, such as hemochromatosis, a condition in which excessive iron is absorbed and deposited into the liver and other organs, and Wilson's disease, caused by the abnormal storage of copper in the liver Although less likely, other causes of cirrhosis include reactions to prescription drugs, prolonged exposure to environmental toxins, or parasitic infections.

What are the Symptoms of Cirrhosis of the Liver?

The symptoms of cirrhosis of the liver vary with the stage of the illness. In the beginning stages, there may not be any symptoms. As the disease worsens, symptoms may include:

• Loss of appetite
• Lack of energy (fatigue), which may be debilitating
• Weight loss or sudden weight gain
• Bruises
• Yellowing of skin or the whites of eyes (jaundice)
• Itchy skin
• Fluid retention (edema) and swelling in the ankles, legs, and abdomen (often an early sign)
• A brownish or orange tint to the urine
• Light colored stools
• Confusion, disorientation, personality changes
• Blood in the stool / vomiting
• Fever

What is the Treatment for Cirrhosis of the Liver?

Although there is no cure for cirrhosis of the liver, there are treatments available that can stop or delay its progress, minimize the damage to liver cells, and reduce complications. The treatment used depends on the cause of cirrhosis of the liver.

• For cirrhosis caused by alcohol abuse, the person must stop drinking alcohol to halt the progression of cirrhosis.
• If a person has hepatitis, the doctor may prescribe steroids or antiviral drugs to reduce liver cell injury.
• For people with cirrhosis caused by autoimmune diseases, Wilson's disease, or hemochromatosis, the treatment varies.

Medications may be given to control the symptoms of cirrhosis. Edema (fluid retention) and ascites (fluid in the abdomen) are treated, in part, by reducing salt in the diet. Drugs called diuretics are used to remove excess fluid and to prevent edema from recurring. Diet and drug therapies can help improve the altered mental function that cirrhosis can cause. Laxatives such as lactulose may be given to help absorb toxins and speed their removal from the intestines. Liver transplantation may be needed for some people with severe cirrhosis.

How Can I Prevent Cirrhosis of the Liver?

There are several ways to reduce your risk of developing cirrhosis of the liver:

• Don't abuse alcohol. If you do drink alcohol, limit how much you drink and how often. Remember, it's not only the heavy drinker who gets cirrhosis. If you drink more than 2 drinks a day, you are increasing your risk. A drink is a 5-oz glass of wine, a 12-oz can of beer, or a 1 1/2-oz portion of hard liquor.
• Avoid high-risk sexual behavior such as unprotected sexual contact with multiple partners.
• Be careful around synthetic chemicals, such as cleaning products and pesticides. If you come into contact with chemicals often, wear protective clothing and a facemask.
• Get vaccinated against hepatitis B.
• Eat a well-balanced, low-fat diet high in fruits and vegetables and take vitamins.
• Maintain a healthy weight, because excess body fat can cause fatty liver, which may lead to liver disease.