Initial symptoms are nonspecific and flu-like, common to almost all acute viral infections, and may include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea, and headache. More specific symptoms, which can be present in acute hepatitis from any cause, are profound loss of appetite, aversion to smoking among smokers, choluria (dark urine), jaundice (yellowing of the eyes and skin), and abdominal discomfort. Before patients develop jaundice, physical findings are uncommon. However, 5-10% of people with hepatitis develop tender enlargement of the liver, enlarged lymph nodes, and enlargement of the spleen. Acute viral hepatitis is more likely to be asymptomatic in children. General symptoms may last for 1–2 weeks before jaundice develops, with the total illness lasting weeks.
A small proportion of people with acute hepatitis progress to acute liver failure, in which the liver is unable to remove harmful substances from the blood (leading to confusion and coma due to hepatic encephalopathy) and produce blood proteins (leading to peripheral edema and bleeding).
Chronic hepatitis may cause nonspecific symptoms such as malaise, tiredness, and weakness, and often leads to no symptoms at all. It is commonly identified on blood tests performed either for screening or to evaluate nonspecific symptoms. The presence of jaundice indicates advanced liver damage. On physical examination there may be enlargement of the liver.
Extensive damage to and scarring of liver (i.e., cirrhosis) leads to weight loss, easy bruising and bleeding, peripheral edema (swelling of the legs), and ascites (accumulation of fluid in the abdomen). Eventually, cirrhosis may lead to various complications: esophageal varices (enlarged veins in the wall of the esophagus that can cause life-threatening bleeding), hepatic encephalopathy (confusion and coma), and hepatorenal syndrome (kidney dysfunction).
Acne, abnormal menstruation, lung scarring, and inflammation of the thyroid gland and kidneys may be present in women with autoimmune hepatitis. Hepatitis associated aplastic anemia may occur 2–3 months after an acute attack of hepatitis.
Types of Hepatitis
The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, hepatitis B, hepatitis C, hepatitis D (which requires hepatitis B to cause disease), and hepatitis E.
Hepatitis B is the most common viral hepatitis worldwide, affecting as much as 10% of the adult population in endemic areas and causing approximately 780,000 deaths per year worldwide. It is most often transmitted vertically in areas of high incidence (perinatally) from mother to baby during birth) or horizontally by being exposed to infected blood or blood products. While less common, Hepatitis B can also be spread through exposure to mucous membranes. A vaccine is routinely given in the developed world to prevent infection.
In the United States, Hepatitis C has become the most common viral hepatitis since widespread vaccination for Hepatitis B in the mid-1980s. It affects an estimated 3.2 million adults living in the United States. Roughly 60-70% of HCV-infected adults living in the United States are unaware of their infection. Even following decades without symptoms, HCV-infected persons remain a source of transmission to others and they are also at elevated risk for developing chronic liver disease and/or other chronic HCV-related diseases.
Excessive alcohol consumption is a significant cause of hepatitis and liver damage (cirrhosis). Alcoholic hepatitis usually develops over years-long exposure to alcohol. Alcohol intake in excess of 80 grams of alcohol a day in men and 40 grams a day in women is associated with development of alcoholic hepatitis. Alcoholic hepatitis can vary from mild asymptomatic disease to severe liver inflammation and liver failure. Symptoms and physical exam findings are similar to other causes of hepatitis. Laboratory findings are significant for elevated transaminases, usually with elevation of aspartate transaminase (AST) in a 2:1 ratio to alanine transaminase (ALT).
Alcoholic hepatitis may lead to cirrhosis and is more common in patients with long-term alcohol consumption and those infected with hepatitis C. Patients who drink alcohol to excess are also more often than others found to have hepatitis C. The combination of hepatitis C and alcohol consumption accelerates the development of cirrhosis.
Toxic and drug-induced hepatitis: Hepatotoxicity
A large number of medications and other chemical agents can cause hepatitis. In the United States acetaminophen, antibiotics, and central nervous system medications are among the most common causes of drug-induced hepatitis. Acetaminophen, also known as paracetamol, is the leading cause of acute liver failure in the United States. Herbal remedies and dietary supplements may also cause hepatitis; these are the most common causes of drug-induced hepatitis in Korea. Risk factors for drug-induced hepatitis include increasing age, female sex, and previous drug-induced hepatitis. Genetic variability is increasingly understood as a key predisposing risk factor to drug-induced hepatitis.
Toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disrupting cell metabolism, and inducing structural changes. Some medications, like acetaminophen, cause predictable dose-related liver damage, whereas others cause idiosyncratic reactions that vary among individuals.
Exposure to other hepatotoxins can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. Occupational exposure may occur in many work fields and can present acutely or insidiously. Mushroom poisoning is a common toxic exposure that may result in hepatitis.
Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells. The disease is thought to have a genetic predisposition as it is associated with certain human leukocyte antigens. The symptoms of autoimmune hepatitis are similar to other hepatitides and may have a fluctuating course from mild to very severe. Women with the disease may have abnormal menstruation or become amenorrheic. The disease occurs in people of all ages but most commonly in young women. Many people with autoimmune hepatitis have other autoimmune diseases.
Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is the occurrence of fatty liver in people who have little or no history of alcohol use. In the early stage there are usually no symptoms, as the disease progresses, symptoms typical of chronic hepatitis may develop. NAFLD is associated with metabolic syndrome, obesity, diabetes, and hyperlipidemia. Severe NAFLD leads to inflammation, fibrosis, and cirrhosis, a state referred to as non-alcoholic steatohepatitis (NASH). Diagnosis requires excluding other causes of hepatitis, including excessive alcohol intake. While imaging can show fatty liver, only liver biopsy can demonstrate inflammation and fibrosis characteristic of NASH. NASH is recognized as the third most common cause of liver disease in the United States.
Injury to liver cells due to insufficient blood or oxygen results in ischemic hepatitis (or shock liver). The condition is most often associated with heart failure but can also be caused by shock or sepsis. Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT). The condition usually resolves if the underlying cause is treated successfully. Ischemic hepatitis rarely causes permanent liver damage.
Giant Cell Hepatitis
Giant cell hepatitis is a rare form of hepatitis that predominantly occurs in newborns and children. Diagnosis is made on the basis of the presence of multinucleated hepatocyte giant cells on liver biopsy. The cause of giant cell hepatitis is unknown but the condition is associated with viral infection, autoimmune disorders, and drug toxicity.