Liver Disease

What is Liver Disease? Symptoms & Causes

The liver is an organ with many vital functions. It's involved in ndigesting food, processing toxins and medications, and distributing nnutrients to the body.1 Liver disease refers generally to the variety of diseases that can affect the liver.2


Mostn conditions discussed in this article cause chronic (long-term) liver ndisease. Some result in acute (short-term) or acute-on-chronic illness.3-4n Liver disease represents a group of common conditions that are nimportant to understand, identify, and prevent. Liver disease in nchildren also has unique considerations.


The Centers for Disease nControl and Prevention (CDC) estimates that 4.5 million people, or 1.8 npercent of the US population, are diagnosed with chronic liver disease nor cirrhosis.5 It’s estimated that as many as 80 million people have liver disease without knowing it.14


Thisn group of conditions is the ninth leading cause of death in the US. nGlobally, chronic liver disease (CLD) caused 1.37 million deaths in 2017n and was more common in men than women.6 Improved prevention and treatment for viral hepatitis has decreased liver-related deaths in recent years.


Acuten liver failure (ALF) is rarer than chronic liver disease, causing nillness in less than 0.001 percent of people in high-income countries.7 However, ALF from viral hepatitis remains a significant risk in lower-income countries.


Symptoms, Signs, and Stages of Liver Disease

Symptoms and signs of liver disease depend on the timing (acute vs. chronic) and stage of the condition.


Symptoms can be nonspecific (shared with other diseases) and vary based on the disease stage.8 Liver disease is divided into four stages9-10:


  1. Hepatitis (liver inflammation): Some inflammation in the liver is healthy, but when it becomes a problem, it’s referred to as hepatitis.
  2. Fibrosisn (scarring): Scarring or stiffening occurs in chronic liver disease due nto long-term hepatitis and results from high levels of collagen n(connective tissue protein) buildup.
  3. Cirrhosis (severe scarring): Permanent damage to the liver caused by severe scarring.
  4. Liver Failure: When the liver fails, it’s not performing vital functions. Liver failure can result from acute (usually happening within days11) or chronic (progressing over years through the four stages) liver disease and usually requires a liver transplant.


Hepatitis causes a range of symptoms and signs9:


  • Swelling of the belly
  • Confusion
  • Diarrhea
  • Nausea
  • Changes in urine color (usually dark)
  • Fatigue (low energy)
  • Itchy skin
  • Joint pain
  • Low appetite
  • Malaise (a general feeling of discomfort) and lethargy (severe lack of energy)
  • Jaundice (yellow skin and eyes)
  • Fever
  • Headache


If you have mild-to-moderate liver disease with fibrosis, you likely won’t notice any symptoms.9 Instead, these symptoms are more common in people with cirrhosis and are discussed in another article.


Acute Liver Failure

Acute liver failure starts with symptoms of acute liver injury.11 These symptoms are similar to those of hepatitis and then worsen:


  • Hepatic encephalopathy, which refers to11:
    • Confusion
    • Flapping hands when arms are held up
    • Coma (unconsciousness)
  • Fluid buildup in the belly
  • Swelling of the arms and legs
  • Blood clotting issues


Hepaticn encephalopathy may initially show up as a change in personality, nforgetfulness, changes in sleep patterns, and irrational or violent nbehavior.11


Chronic Liver Failure

Chronic liver failure (CLF) symptoms result from long-term cirrhosis.12 When people develop symptoms of CLF, they have decompensated cirrhosis. Symptoms include:


  • Fluid buildup in the belly
  • Hepatic encephalopathy
  • Bleeding from the stomach or intestines


Liver Cancer

The symptoms of liver cancer can look like other illnesses and usually don’t show up until later stages of the disease.13 In someone with a history of liver disease or who has risk factors, these symptoms and signs may point to liver cancer:


  • Unintentional weight loss
  • Decreased appetite
  • Feeling full after a small meal
  • Nausea or vomiting
  • An enlarged liver (mass under the ribs on the right side)
  • An enlarged spleen (mass under the ribs on the left side)
  • Belly pain
  • Swelling of the belly
  • Itchy skin
  • Jaundice


Causes of Liver Disease and Risk Factors

Theren is a fair amount of overlap between risk factors for and causes of ncertain liver conditions. However, a risk factor is not always a cause. nThe most common risk factors for developing liver disease are also the nmost common causes of it:


  • Alcohol use: nResearch shows a major increase in the risk of developing liver disease nin people who drink alcohol, especially for those who drink heavily for nmany years.15 Alcohol use causes liver disease by increasing nsteatosis (fat storage in the liver). Steatosis leads to inflammation nand death of liver cells.19
  • High amounts of body fat: The liver stores more fat in people with more body fat, causing disease in some cases.16
  • Metabolic conditions: These include dyslipidemia (high cholesterol, triglycerides), hypertension (high blood pressure), and diabetes
  • Viral infection:n Several viruses increase the risk of liver disease and directly cause nit. Long-term inflammation from the body fighting infection causes livern disease.20


The following factors increase the risk of developing liver disease but are not known to cause it directly:


  • Cigarette smoking: Smoking cigarettes increases the risk of developing liver cancer.17
  • Certain gene changes passed down through family members increase the risk of developing liver disease.17-18
  • IV drug use: Injecting drugs into the blood increases the risk of contracting viruses that can cause liver disease.13
  • Aflatoxin B1:n Exposure to foods containing aflatoxin B1 (a poison that can grow on nfoods that are kept in humid places) increases the risk of liver cancer,n most commonly in sub-Saharan Africa, southeast Asia, and China.17


Types of Liver Disease

Livern disease shows up differently depending on the cause. Knowing the uniquen characteristics of each type helps to find the right treatment. Here nare the most common types of liver disease in adults.


Viral Hepatitis

Viral hepatitis can be acute or chronic.20n The viruses that cause it are hepatotropic viruses (viruses that targetn liver cells directly, named hepatitis A through E), Epstein-Barr virus,n herpes simplex virus, and cytomegalovirus. Most deaths from this type nof liver disease are caused by chronic hepatitis B and C.


Alcohol-Associated Liver Disease

There are three stages of alcoholic liver disease, starting with steatosis, progressing to hepatitis, and then cirrhosis.19n Once cirrhosis develops, hepatocellular carcinoma (liver cancer) may nfollow. Alcohol-associated liver disease is one of the leading causes ofn liver disease in the United States, along with nonalcoholic fatty nlivery disease, or NAFLD.


NAFLD (Nonalcoholic fatty liver disease)

Nonalcoholic fatty liver disease (NAFLD) is defined as the buildup of fat in at least 5 percent of liver cells without another cause for it.21n NAFLD includes NAFL (nonalcoholic fatty liver disease) and NASH n(nonalcoholic steatohepatitis). NASH is characterized by inflammation ncaused by fat buildup in the liver. NASH can lead to fibrosis, ncirrhosis, and hepatocellular carcinoma. NASH can be related to high nbody fat percentage and metabolic conditions such as diabetes, high nblood pressure, hyperlipidemia (high cholesterol and ntriglycerides) toxin exposure, or drugs.


Autoimmune Hepatitis

The two known types of autoimmune hepatitis (Type 1 and Type 2) are defined by the presence of certain antibodies in your blood.23n Antibodies are proteins made by the immune system to attack foreign nsubstances. Autoimmune hepatitis may result from a combination of ngenetic risk, environmental triggers, and low immune system response. nThis leads to inflammation and fibrosis of the liver.


Primary Biliary Cholangitis (PBC)

PBCn is a chronic liver disease where small bile ducts (tubes that carry nbile through the liver to the gallbladder to store or to the first part nof the intestines for digestion) inside the liver are inflamed.24 Over time, the ducts are destroyed, bile builds up in the liver, and liver function suffers.25n The exact cause isn’t known, but research points to genetics and ncertain triggers that cause the immune system to attack bile ducts.


Primary Sclerosing Cholangitis (PSC)

Primary sclerosing cholangitis (PSC) is a chronic liver disease that also affects bile ducts.26n In PSC, bile ducts within and outside the liver are inflamed and becomen scarred, causing bile buildup in the liver and liver damage. Like PBC, nthe cause of PSC isn’t known.27 Research suggests that genetics, immune system issues, bacterial changes in the gut, and injury to bile ducts may be involved.


Hemochromatosis

Hemochromatosis is a disorder that causes a harmful buildup of iron in the body from absorbing too much iron from the diet.28n The body needs a certain amount of iron to make red blood cells, nmuscle, and heart cells. However, when the body has too much, it can ncause organ damage. Certain genetic mutations cause hemochromatosis.29


Alpha-1 Antitrypsin (AAT) Deficiency

Alpha-1 Antitrypsin (AAT) deficiency is a genetic disorder caused by low production of alpha-1 antitrypsin protein.30n AAT protein protects the body from an enzyme that is released by white nblood cells during infection. Without this protein, the enzyme attacks nlung cells, causing lung disease. The dysfunctional AAT protein can alson accumulate in the liver, causing liver disease.


Drug-Induced Liver Injury (DILI)

Some medications, herbals, vitamins, supplements, and drugs can cause liver damage.


Diagnosis and Testing of Liver Disease

Diagnosing liver disease starts with a detailed history and exam completed by a doctor.31n A doctor will ask questions about your symptoms and complete an exam nlooking for signs of liver disease. They will also ask about medical andn family history, looking for conditions that increase the risk of liver ndisease.


Blood Testing for Liver Disease

Because early nliver disease is usually asymptomatic, testing is usually needed to maken a diagnosis. When liver disease is a concern, certain blood tests are nordered8:


  • Liver tests: Measure nliver enzymes (proteins that speed up chemical reactions in the body), nsuch as albumin, aspartate transaminase (AST), alanine transaminase n(ALT), alkaline phosphatase (ALP), or bilirubin (a substance produced inn the spleen when blood cells are broken down and processed by the nliver). A common test of liver function is the international normalized nratio (INR) test, which measures your blood’s clotting ability, which nrelies in part on a liver-produced protein called prothrombin.
  • Fibrosis blood tests: Combines multiple lab tests to provide a general idea of the level of fibrosis in the liver.
  • Viral tests: Used to identify viral infections, including hepatitis A through E, cytomegalovirus (CMV), and Epstein-Barr virus.
  • Iron studies: Measure the level of iron and related proteins in the body, which can help diagnose hemochromatosis.
  • Autoimmune tests: Used to identify autoimmune hepatitis, PBC, and PSC.
  • Alpha-1 antitrypsin: Measures the protein affected in AAT deficiency to diagnose this condition.


Imaging Tests for Liver Disease

Imaging is another important part of diagnosing liver disease.8


  • Ultrasoundsn (US): US images are created by passing sound waves through a part of nthe body. US of the abdomen (belly) is one of the most common initial ntests used to characterize liver disease. US shows the size and amount nof fibrosis or scarring of the liver to help diagnose cirrhosis.
  • Computed tomography (CT) and magnetic resonance imaging (MRI):n CT scans use multiple X-rays to image internal organs. CTs can show nliver tumors/masses or blockage in the bile ducts. MRI uses magnets to nimage the liver and is better than CT at diagnosing cancer, nhemochromatosis, and steatosis.35
  • Transient elastography (TE or fibroscan):n This is a special type of ultrasound. TE is used to diagnose early ncirrhosis by measuring how high-speed sound waves move through the nliver. The waves move faster through stiffer tissue, helping to identifyn a scarred liver.
  • Liver biopsy: A biopsy takes an small piece of tissue from the liver to look at under a microscope. nIt’s used in situations where your doctor suspects liver disease and nwants to confirm it, or for a more specific assessment of how damaged nthe liver is.32 Biopsies can be taken through the skin, through the belly in a surgical procedure, or through a neck vein.8


Complications of Liver Disease and Effects on the Body

Some liver diseases, like infection with hepatitis A, can cause short-lived illness that has no long-term effects.33 However, liver disease usually causes chronic illness.8n Chronic liver disease can affect organs other than the liver, nespecially when liver function suffers significantly. The most common ncomplications of liver disease are portal hypertension, hepatocellular ninsufficiency, and hepatocellular carcinoma, as described below.


Portal Hypertension

Portal hypertension is high blood pressure in the vein that feeds blood to the liver.8n When a liver becomes scarred, the blood has a harder time moving nthrough it, creating high pressure in blood vessels. The most common ncause of portal hypertension is cirrhosis. Symptoms of this condition ninclude:


  • Swelling in the blood vessels of the esophagus and stomach
  • Swelling in the veins around the belly button
  • Swelling in the rectal veins
  • Fluid buildup in the belly


Anytimen blood vessels get swollen, they are more likely to bleed or cause pain.n Importantly, ascitic fluid (fluid buildup in the belly) can become ninfected and cause spontaneous bacterial peritonitis (SBP). This ncomplication of liver disease is life-threatening and treated with nintravenous antibiotics.


Hepatocellular Insufficiency

Hepatocellular insufficiency means that liver cells are not functioning normally.8n Liver cells are important for detoxification. When liver cells aren’t nworking, harmful substances like ammonia (a substance made when proteinsn break down) can build up. High levels of ammonia in the blood leads to nconfusion, abnormal movements, and loss of consciousness. Because the nliver makes important proteins, other problems can occur, such as nbleeding and clotting.


Hepatocellular Carcinoma (HCC)

Hepatocellularn carcinoma (HCC)—the fifth most common cause of cancer nworldwide—develops in people diagosed with cirrhosis at a rate of about n1.5% annually.22,23 The types of liver diseases that cause HCC are hepatitis B and C, alcoholic liver disease, and NAFLD/NASH.


Prevention of Liver Disease

Inn cases where someone has a genetic liver disease, prevention may not be npossible. However, many of the liver diseases discussed here can be nprevented with the right strategies35:


  • Eat a balanced diet with fruits, vegetables, and healthy (unsaturated) fats
  • Exercise regularly
  • Avoid alcohol
  • Take medications as prescribed
  • Screen for hepatitis B and C
  • Treat related conditions, like diabetes, hepatitis B and C, and NASH
  • Get the hepatitis B vaccine


Resources for Living with Liver Disease

Ifn you or a loved one is living with liver disease, there are many nresources that can support you. Look at these resources to get started:



Medical Disclaimer: Then information provided in this article is not a substitute for the advicen of qualified healthcare professionals. While we strive to publish naccurate information, it is not possible to cover all potential nscenarios, including drug or treatment effects, interactions, or usage. nYou should not rely solely on this article to determine whether a nparticular treatment, drug, or clinical trial is suitable for you or anyn other individual. Always consult a healthcare professional before nstarting or changing any treatments.

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