Liver Disease

Liver diseases are a major cause of morbidity and mortality across the globe. Any abnormality with respect to the liver's structure, position, enzyme secretion and other functions is known as a liver disease. Most common causes of liver disease include excessive alcohol intake, viral and parasitic infections, and obesity. If these agents continually injure the liver, it can result in cirrhosis (liver scarring ) and gradually lead to liver failure, which is a life-threatening condition.

Alcoholic Liver Disease (ALD)

It is the most common liver disease and occurs due to excessive and regular alcohol intake. Alcohol acts as a poison to the liver and causes its inflammation. There is an accumulation of fat in the liver resulting in fatty liver. This fat accumulation affects liver functioning and causes symptoms like jaundice, nausea, vomiting, and enlarged veins in the food pipe (oesophageal varices). This eventually leads to irreversible damage to the liver called cirrhosis.

Non-alcoholic Steatohepatitis (NASH)

It is the second most common form of liver injury. The most common causes of NASH are obesity and uncontrolled diabetes, which result in injury to the liver cells and cause accumulation of fat in the liver cells. Symptoms of NASH are same as ALD, only the causes are different. If left untreated, it can result in liver cirrhosis and failure.

Viral Hepatitis 

It is more common in developing countries. Infection by viruses, such as hepatitis A and hepatitis E results in acute liver injury. Hepatitis A and E infections are usually caused by eating food or beverages contaminated with these viruses. It results in jaundice, fever, nausea, vomiting, and abdominal pain. Infection with viruses like hepatitis B, hepatitis C, and hepatitis D can gradually damage the liver and cause chronic liver injury. These are blood-borne infections and spread through infected blood, use of infected needles-syringes, and sexual intercourse. Symptoms of viral liver infection appear gradually and present as slowly developing jaundice.

Hemochromatosis 

It is one of the rare forms of metabolic liver disease where the body accumulates excess iron in the blood, as well as the liver. Iron accumulates in the liver cells damaging it and causing liver inflammation, cirrhosis, and eventually, liver failure or liver cancer if left untreated.

Primary Biliary Cholangitis 

It is one of the rarest forms of liver disease, which is caused due to a faulty immune system that damages the bile ducts. The damaged bile ducts (small tubes that collect bile from liver cells) are unable to transport the bile to the gallbladder. Hence, these contents accumulate in the liver and damage the liver cells. If left untreated, it can lead to cirrhosis and eventually liver failure. This disease was earlier thus called as primary biliary cirrhosis. 

Liver disease have multiple causative factors with lead to a different presentation of each liver disease. However, there is a fixed pattern in which these diseases progress and damage the liver. The stages of a liver disease are:

Inflammation

It is the first stage of liver disease in which the liver becomes inflamed or swollen. Inflammation can make the liver painful and enlarged (hepatomegaly). It indicates that your body is trying to heal the injury. If liver injury continues unchecked longer, it can cause permanent liver damage. This stage of liver disease is completely reversible.

Fibrosis

If inflammation of liver cells continues, then the cells start getting repaired with scar tissue, resulting in scarring of the liver. A scarred liver is not able to perform its functions well. If the extent of scarring increases in the liver, it may cause permanent liver damage. This fibrosis stage is partially reversible.

Cirrhosis

If the fibrotic stage remains unchecked, then the soft liver scar is replaced by a hard-scar tissue. During this stage, most functions of the liver are compromised, and it can lead to several complications, including liver cancer and liver failure.

Liver Failure

The last stage of any liver disease that has been left untreated is liver failure. This is a life-threatening condition that requires immediate care and hospitalization. If left untreated, it can lead to coma and eventually death.

The early phase of liver disease hardly shows any symptoms, and even if they are present, they are vague and non-specific. Yet, there are certain common symptoms that appear during either injury or repair of the liver cells.

Acute liver injury or acute hepatitis shows symptoms such as:

• High-grade fever.
• Nausea.
• Vomiting.
• Jaundice.
• Itchy skin.
• Dark yellow urine.
• Yellowing of the whites of the eye.

Symptoms of a chronic liver disease include:

• Jaundice
• Abdominal pain and swelling.
• Nausea.
• Vomiting.
• Swelling over ankles and legs.
• Itching.
• Spider naevi (small red, spider-like appearance of the blood vessels on the skin).
• Loss of appetite.
• Weight loss.
• Weakness even with minimal activity.
• Easy bruising.

If liver disease advances to the cirrhotic phase, then new symptoms may develop, such as:

• Blood in vomit (hematemesis).
• Bleeding from the anus.
• Accumulation of fluid in the abdomen (ascites).
• Confusion.

Certain liver diseases might show unique symptoms pertaining to that condition in addition to some of the above-mentioned signs and symptoms. If cirrhosis remains untreated, it progresses to liver failure, which is a medical emergency and can present as stupor, and coma along with symptoms, such as severe disorientation, confusion, and bad breath.

Causes 

The most common causes of liver disease are alcohol and obesity. There are some other rare causes that can affect the liver and injure it.

Causes of liver diseases include:

• Alcohol abuse
  As mentioned above, alcohol slowly deteriorates the liver by causing the deposition of fat in the liver cells, thus reducing their function.
• Obesity
  Obesity also results in the deposition of fat in the liver, which causes a large number of hepatitis cases, also known as steatohepatitis.
• Infection 
  Viral and parasitic infections can damage liver cells and cause acute or chronic injury. These include:
  • Hepatitis A virus
  • Hepatitis B virus
  • Hepatitis C virus
  • Hepatitis D virus
  • Hepatitis E virus
  • E. histolytica infection causing liver abscess where there is an accumulation of pus in the liver.
• Immune system disorders
  Conditions where the function of the immune system is hampered and they affect the liver cells or cells of the bile duct causing liver injury include:
  • Autoimmune hepatitis
    It is a condition where the body’s immune system attacks the liver tissue considering it to be a harmful agent. It results in swelling and distention of the abdomen.
  • Primary sclerosing cholangitis
    This is an autoimmune disorder where the bile ducts get blocked due to the accumulation of collagen (a type of fibrous tissue).
  • Primary biliary cholangitis
• Genetic 
  An abnormal gene can result in changes or reduction in the in the enzymes or proteins produced by the liver. These altered substances can damage your liver and cause liver disease.
  • Hemochromatosis
    In this condition, there is an accumulation of excess iron in the liver.
  • Wilson’s disease
    Wilson's disease is characterised by an accumulation of excess copper in the liver.
  • Gilbert’s disease 
    This is a genetic disorder where there is an abnormal metabolism of bilirubin pigment and because of that jaundice remains persistent.
  • Alpha-1 antitrypsin deficiency  
    It is a genetic disorder causing the deficiency of alpha-1 antitrypsin enzyme.
• Cancer 
  Cancer is commonly seen in people who have reached beyond the cirrhotic stage of liver disease. The most common causes are hepatitis B & hepatitis C viruses. Some of the cancers associated with the liver are:
  • Liver cancer
  • Bile duct cancer

Risk Factors 

There are many risk factors that can make one prone to liver diseases. These are:

• Excessive alcohol intake.
• A family history of genetic liver diseases, such as Wilson’s disease.
• Obesity.
• Use of unsterilized needle or syringes (commonly seen amongst drug abusers).
• Prolonged uncontrolled diabetes.
• Blood transfusion.
• Unprotected sex. (Read more - How to have safe sex)
• Exposure to poisons and toxins.
• Frequent use of painkillers, such as NSAIDs (non-steroidal anti-inflammatory drugs) or steroids.
• Healthcare workers are at high risk of acquiring hepatitis B and C infections.

Liver diseases can be prevented. Here are the certain lifestyle and dietary modifications that can help in preventing liver disease:

• Avoid alcohol or consume in moderation
  Taking one drink for women and two drinks for men per week is considered safe and may not result in liver injury; yet, it is always better to avoid alcohol intake.
• Get vaccinated
  Vaccines against hepatitis A and B virus are available and have very high efficacy.
• Use medicines wisely
  Avoid excessive and prolonged use of drugs that are known to be hepatotoxic (toxic to the liver) like acetaminophen, methotrexate, statins, anti-TB drugs and others.
• Avoid the use of aerosol sprays
  Insecticide and fungicide sprays, if inhaled for prolonged duration accumulate in our body and eventually, damage the liver.
• Manage body weight
  Maintaining an ideal Body Mass Index (BMI) can reduce the risk of developing NASH.
• Use sterilized intravenous needles and practice safe sex
  Use of intravenous drugs with unsterilized needle and syringes or reusing them can spread hepatitis B and C viruses. Unprotected sex can also make one prone to these infections.

In most cases, the person’s symptoms suggest the presence of a liver disease. But, it is equally important to find out the underlying cause and extent of the disease, which requires several investigative tests. These are:

• Physical Examination
  A detailed medical history along with a thorough physical examination of the abdomen help in diagnosing the condition. Physical examination shows little tightness and tenderness in the upper part of the abdomen. The liver might be enlarged. Also, yellowish discolouration of the skin and the eyes suggest jaundice (icterus).
• Blood test
  Liver function test is the key to diagnose many conditions of the liver and can suggest the extent of liver injury. Liver function tests include evaluation of liver enzymes, which encompass:
  • Alkaline Phosphatase (ALP/SGPT)
  • Alanine Transaminase (ALT)
  • Aspartate Transaminase (AST/SGOT)
  • GGTP (gamma-glutamyl transferase)
  • Total Bilirubin (Direct bilirubin & Indirect bilirubin)
  • Total proteins (Albumin and Globulin)

Other blood tests like those for detecting hepatitis viruses, high copper and iron levels, might be done when these conditions are suspected.

• Imaging tests 
  Imaging techniques include an abdominal ultrasound and CT scan. While an abdominal ultrasound can provide details about the structure of the liver, a CT scan is more conclusive as it can indicate the extent of liver injury, as well as show the internal architecture of the liver. In certain people, radioactive copper-based CT scan evaluation is performed to determine the extent of the injury.
• Biopsy or tissue analysis 
  In certain cases, when the cause of liver injury or disease cannot be ascertained based on clinical findings, it becomes mandatory to study the microstructure of the liver cells in order to employ the correct and effective line of treatment. In such cases, a biopsy is performed by inserting a long-needled syringe to take out the liver tissue sample and is studied under the microscope.

Liver diseases are treated as per the diagnosis. In certain advanced cases, when curative treatment is not applicable, palliative treatment is prescribed to reduce the severity of symptoms or to prevent the morbidity due to complications. Some of the frequently employed treatment methods include:

• Antiviral Therapy
  Long-standing hepatitis B and C viral infections are treated with antiviral drugs that are usually prescribed for a long duration.
• Antibiotic Therapy
  Liver abscess needs oral antibiotic therapy, but in severe cases, pus drainage and intravenous antibiotics are required for quick and complete recovery.
• Combination Therapy
  It is employed in the cases of autoimmune hepatitis. In this therapy, a combination of corticosteroids, immunosuppressive and anti-inflammatory drugs are given. These medicines reduce the overactivity of the immune system and swelling in the liver.
• Chelation Therapy 
  In the case of Wilson’s disease, copper is chelated using penicillamine class of drugs. The ions of copper bind to the drug and are excreted in urine. Off late, Trientine is used as it has fewer side effects.
• Repeated Phlebotomy
  This is done in the case of hereditary hemochromatosis. Phlebotomy is a procedure in which blood is removed from a vein in the body to lower the high iron levels.
• Supportive therapy
  Certain liver enzymes or proteins are given as supportive drugs to reduce the burden on the liver cells.
• Surgery or Liver Transplant  
  If the disease is severe and incurable, a liver transplant is performed; it may be a cadaveric – whole liver transplant or partial liver-tissue transplant from a living donor.

In a majority of the cases, combination therapy along with lifestyle modification help to treat liver diseases.  Regular and careful monitoring of liver function and ultrasound evaluations are also important.

Lifestyle management

Liver disease can affect a person’s normal daily routine. Especially, the chronic complaints need quite a lot of lifestyle modifications to avoid further progression of the disease and associated complications. Some diseases are treated with lifestyle modifications, such as stopping alcohol intake, losing weight, and attaining an ideal BMI. Lifestyle modifications for liver disease include:

• Limit alcohol intake
  Since alcohol is one of the most common causes of developing or worsening a liver disease, it is always advised to limit the intake of alcohol or stop it entirely.
• Meal plans
  Try eating smaller meals frequently throughout the day, as large meals or meals rich in fats may increase the burden on the liver causing further damage.
• Diet modification
  The liver is associated with protein metabolism and disorders of the liver can hamper it. So, it is important to include more carbohydrates in the diet, which help in providing energy for a long duration. Eating proteins should be avoided as they may not get adequately metabolised by the liver. As a result, some toxic byproducts may accumulate in the body and affect the brain. In people with hemochromatosis, vitamin C intake should be limited as it increases the absorption of iron from the diet.
• Use of analgesics or painkillers
  Almost all the painkillers are metabolized in the liver and most of them are hepatotoxic (have certain harmful effects on the liver). So, it is always better to avoid any form of painkillers and should take them only after a doctor’s consultation.
• Avoid smoking
  Smoking is also one of the known factors to cause liver damage. So, to avoid further liver injury, it is better to avoid smoking.
• Weight management
  Losing weight or achieving target BMI works well to reduce fat accumulation and further damage to the liver. At the same time, it can also help to prevent associated complications. (Read more - Weight loss diet chart)
• Vaccination
  A damaged liver is more prone to get affected by hepatitis viruses and viral infection can bring about cancerous changes in the liver; so vaccinating yourself against hepatitis virus is important to avoid complications.

Prognosis

Acute liver diseases, especially those that are caused by hepatitis A & E viruses, are easy to treat and recovery is quick. However, chronic infections like hepatitis B & C viruses have a relatively poor prognosis and the treatment continues for a longer duration. Alcoholic liver disease and obesity-related liver disease (NASH) in early phases i.e., hepatitis and fibrotic phase have very good prognosis if treated in time. Once cirrhosis sets in, prognosis worsens. Liver failure can be life-threatening and has a very poor prognosis.

Complications 

As the liver has one of the most significant roles in metabolism, liver damage can lead to several complications and can involve multiple organ systems. These complications include:

• Portal Hypertension
  Blood pressure inside the portal vein (a vein that carries blood to the liver from organs such as the spleen, pancreas, gallbladder, and gut) increases (portal hypertension) and this can lead to varices (enlargement of smaller veins of the stomach, oesophagus, and sometimes of the rectum).
• Varices and Variceal bleeding
  These small vessels, which become enlarged due to portal hypertension, can rupture and bleed. Minor bleeding can result in melena (blood in stools) and anaemia. Variceal bleeding can also cause hematemesis (blood in vomit), which can be a life-threatening condition
• Ascites
  A chronic liver disease affects protein metabolism and causes portal hypertension, which can result in the leakage and accumulation of fluid in the abdomen, known as ascites. If ascites is not treated completely (drained off well), it can become infected and be life-threatening.
• Encephalopathy
  Hepatic encephalopathy is a late complication of liver disease. It occurs when the liver undergoes cirrhosis and causes symptoms like mental confusion (delirium), disorientation, muscle tremors, stiffness, and slurring of speech. In severe cases, it can lead to coma or even death.
• Liver Cancer
  People suffering from liver cirrhosis have a higher risk of developing liver cancer. This happens due to changes that can take place in the dead liver cells. Liver cancer can lead to liver failure.