Liver Helpline

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Systemic conditions associated with liver damage

Some patients with liver damage can have underlying systemic diseases, which may also affect liver function. Knowledge of liver involvement in systemic diseases is important for the accurate diagnosis of the liver damage and guide appropriate treatment.

    Cardiovascular diseases

    Ischemic Hepatitis

    Ischemic hepatitis is a condition that can happen rapidly (within 24-48 h) leading to a “shock liver”. This is caused by several heart conditions including left ventricular failure, heart attack, abnormal heart rhythms, malfunctioning heart valves etc. This can also be caused by severe injury (trauma), burns, or bleeding. There is a dramatic transient increase in liver enzymes (blood aminotransferase, lactate dehydrogenase (LDH) levels and bilirubin levels sending the liver into shock.

    It is important to differentiate ischemic hepatitis from acute viral hepatitis

    • LDH elevation is more marked in in viral hepatitis
    • Liver enzymes serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations rapidly return to normal in ischemic hepatitis, usually within 7-10 d

    Kidney damage is seen with the shock liver of ischemic hepatitis

     Right Heart Failure

    Heart failure patients are unable to fill the heart back into the causing a back –up in the veins.  So that legs, ankles, and the abdomen will often swell up. Most often, the lungs are also affected and the patient will experience difficulty is breathing. Short term (acute) or long term (chronic) right-sided heart failure causes liver congestion with the typical liver damage symptoms of:

    • Enlarged liver (hepatomegaly)
    • Swelling of abdomen with fluid (ascites)
    • Enlargement of the spleen (splenomegaly)
    • Yellowing of skin and whites of the eyes (jaundice) may or may not be present

    Liver function tests are abnormal

    • Serum bilirubin is elevated rapidly return to normal 3-7 d after improvement of right-sided heart failure
    • Elevated levels of serum aminotransferases, with the elevation of AST more marked than that of ALT
    • Elevated serum alkaline phosphatase (ALP) return to normal within 1 wk after improvement of heart failure

    Cardiac cirrhosis is a condition that can occur after longstanding liver congestion, but its incidence is relatively low, the risk increasing with age. Treatment of cardiac cirrhosis is based on managing the heart disease causing it.

    Endocrine Diseases

    Diabetes Mellitus

    Non-alcoholic fatty liver disease (NAFLD), a common condition seen across Asia is a complication in 32% to 78% of patients with type 2 diabetes mellitus (Type 2DM). More than half of these patients progress to non-alcoholic steatohepatitis (NASH), eventually leading to extensive scarring (fibrosis). A vicious circle has been suggested to be the cause and effect in persons with diabetes. NAFLD in itself is not only a result of metabolic syndrome (coexisting hypertension, high cholesterol, obesity and Type 2DM, but also actively promotes the development of metabolic syndrome. The liver plays a key role in regulating both glucose and lipid metabolism, disorders that occur in NAFLD and Type 2DM. The liver damage is more in patients with Type 2DM than type 1 DM. It is recommended that persons with type 2DM monitor their liver for NAFLD.

    • Blood tests for liver enzymes and ultrasound imaging can pick up early NAFLD.

    Thyroid Disease

    Hyperthyroidism, or an overactive thyroid gland frequently experience liver damage. It is believed that there is an increased oxygen demand without a simultaneous increase of blood flow to the liver.

    • Liver injury can be detected by blood tests
    • Elevated serum ALP, and elevated ALT is seen

     Cushing Syndrome

    Nearly 50% of patients will have fatty infiltration of the liver, which may progress to NASH.

    Connective Tissue Diseases

    Liver damage is a common complication of systemic lupus erythematosus (SLE). Chronic hepatitis and liver cirrhosis can occur. It is important to distinguish lupus-related chronic hepatitis from autoimmune hepatitis (AIH). AIH often rapidly progresses to liver cirrhosis unless they are treated with appropriate and sufficient doses of corticosteroids.

    • Anti-smooth muscle antibody, which is found in patients with AIH but not in those with lupus-related liver disease

    Other connective tissue disorders causing liver damage include:

    • Juvenile rheumatoid arthritis
    • Rheumatoid arthritis
    • Feltys syndrome
    • Stills disease
    • Scleroderma

    Blood (Hematological) Disorders

    • Hodgkin ’s Disease/ Lymphoma is a type of cancer of a part of the immune system called the lymph system, hence also called Hodgkin’s lymphoma. The first sign of Hodgkin disease is often an enlarged lymph node, and spread to nearby lymph nodes. In the later stages, it may spread to the lungs, liver, or bone marrow. The exact cause is unknown. A lymph node biopsy confirms the diagnosis.
    • Non-Hodgkin Lymphoma will have lymphoma cell infiltration of the liver and is more common than in Hodgkin disease. Some patients can present with liver failure, but liver transplant should be avoided. The spread to the liver is more common in low-grade B-cell lymphomas than in high-grade lymphomas. The jaundice due to non-Hodgkin lymphoma is different from viral hepatitis or drug hepatotoxicity by the presence of liver enlargement and lactic acidosis in the lymphoma.
    • Chronic Lymphoid Leukemia will often cause mild to moderate liver enlargement and extensive lymphocytic infiltration in the portal tracts, with functional impairment of the liver in late stages.
    • Hairy Cell Leukemia often infiltrates the liver, in both the portal veins and the liver sinusoids. This causes liver enlargement in up to 40% of patients
    • Acute Leukemia commonly causes cancer cells to spread to the liver and may present as fulminant hepatic failure. Associated drug-induced liver injury and bacterial or fungal infections may also affect the liver.
    • Multiple Myeloma is a type of bone cancer; an enlarged liver is seen in up to 40% of patients with possible enlargement of the spleen
    • Chronic Myeloid Leukemia will show mild to moderate liver enlargement at presentation in about 50% of patients, with no liver function abnormalities. Later, immature cancer cells may lead to liver enlargement and elevated serum ALP levels

    Other blood disorders affecting the liver are:

    • Sickle-Cell Disease can cause progressive injury to the liver with significant fibrosis, often cirrhosis, and decreased liver function by adulthood due to iron overload. Asymptomatic patients commonly have enlarged livers and elevated liver enzyme levels
    • Thalassemia is a group of disorders in which there is reduced levels of hemoglobin, decreased red blood cell production, and anemia. Abnormal liver function appears to be due to iron overload often aggravated by viral infection. Hepatic siderosis, portal fibrosis and even cirrhosis may develop despite iron chelation therapy
    • Anemiadue to blood loss, folate (folic acid) deficiency, hemolysis, marrow suppression by alcohol affect the liver

    Lung Diseases

    • Pneumonias caused by Legionella pneumophila, Mycoplasma pneumoniaeor Pneumococcus may be associated with elevated concentrations of serum aminotransferase and bilirubin and jaundice
    • Legionnaire’sdisease, liver function tests are likely to show abnormalities, with elevated concentration of serum ALP and aminotransferase in up to 50% of patients.
    • Cytomegalovirus pneumonia can also result in jaundice and elevated levels of ALP and aminotransferases
    • Chronic pulmonary disease is usually associated with heart failure or hypoxia.

    Kidney Diseases

    • Interestingly renal cancer causes enlargement of the liver and abnormal liver function test results, even when the cancer has not spread to the liver. This is called Stauffer’s syndrome.
    • Rare disorders can directly affect both the kidneys and the liver
      • Carbon tetrachloride toxicity
      • Severe kidney damage and kidney failure of hepatorenal syndrome

    Systemic infection-bacteremia and sepsis

    • The major pathogens are S aureusand coliP aeruginosa infection, with mild elevation of ALP and modest elevation of ALT, and normal ALP levels in deep jaundice. These levels often return to normal when infection in the blood (bacteremia) is treated.
    • perfringensmay directly affect the liver by forming an abscess or causing necrotizing massive gas gangrene of the liver, leading to fulminant liver failure.
    • Salmonella typhi infection can cause Salmonellahepatitis
    • Chlamydia or Neisseria infection
    • HIV infection
    • Tuberculosis in the liver can occur, even in the absence of apparent tuberculosis elsewhere. It is caused by Mycobacterium tuberculosis
    • Lyme disease
    • Syphilis – tertiary syphilis may present with gummas formation in the liver, which resemble metastatic tumors
    • Campylobacter infection
    • Fungal infection by C albicansand  tropicans can enter into the liver from the gut and form multiple small abscesses or granulomas in the liver.

    Abnormal liver function tests might be caused by the systemic disease and therefore the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver damage or liver failure require intensive treatments of the liver