Hepatitis

Introduction


Hepatitis implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The condition can be self-limiting, healing on its own, or can progress to scarring of the liver. Hepatitis is acute when it lasts less than six months and chronic when it persists longer. A group of viruses known as the hepatitis viruses cause most cases of liver damage worldwide. Hepatitis can also be due to toxins, other infections or from autoimmune process. The patient becomes unwell and symptomatic when the disease impairs liver functions that include, among other things, removal of harmful substances, regulation of blood composition, and production of bile to help digestion.

Causes

Acute hepatitis

• Viral Hepatitis: Hepatitis A through E (more than 95% of viral cause), Herpes simplex, Cytomegalovirus, Epstein-Barr, yellow fever virus, adenoviruses.
• Non viral infection: toxoplasma, Leptospira, Q fever, rocky mountain spotted fever
• Alcohol
• Toxins: Amanita toxin in mushrooms, carbon tetrachloride, asafetida
• Drugs: Paracetamol, amoxycillin, antituberculosis medicines, minocycline and many others.
• Ischemic hepatitis (circulatory insufficiency)
• Pregnancy
• Auto immune conditions, e.g. Systemic Lupus Erythematosus (SLE)
• Metabolic diseases, e.g. Wilson's disease

Chronic hepatitis

• Viral hepatitis: Hepatitis B with or without hepatitis D, hepatitis C (Hepatitis A and E do not lead to chronic disease)
• Autoimmune: Autoimmune hepatitis
• Alcohol
  
• Drugs: methyldopa, nitrofurantoin, isoniazid, ketoconazole
• Non-alcoholic steatohepatitis
• Heredity: Wilson's disease, alpha 1-antitrypsin deficiency
• Primary biliary cirrhosis and primary sclerosing cholangitis occasionally mimic chronic hepatitis

Signs and symptoms

Acute hepatitis

Acute hepatitis varies widely from mild symptoms requiring no treatment to fulminant hepatic failure needing liver transplantation. Acute viral hepatitis is more likely to be asymptomatic in younger people. Symptomatic individuals may present after convalescent stage of 7 to 10 days, with the total illness lasting 2 to 6 weeks.

Initial features are of nonspecific flu-like symptoms, 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, dark urine, yellowing of the eyes and skin (i.e., jaundice) and abdominal discomfort. Physical findings are usually minimal, apart from jaundice (33%) and tender hepatomegaly (10%). There can be occasional lymphadenopathy (5%) or splenomegaly (5%).

Chronic Hepatitis

Majority of patients will remain asymptomatic or mildly symptomatic, abnormal blood tests being the only manifestation. Features may be related to the extent of liver damage or the cause of hepatitis. Many experience return of symptoms related to acute hepatitis. Jaundice can be a late feature and may indicate extensive damage. Other features include abdominal fullness from enlarged liver or spleen, low grade fever and fluid retention (ascites). Extensive damage and scarring of liver (i.e., cirrhosis) leads to weight loss, easy bruising and bleeding tendencies. Acne, abnormal menstruation, lung scarring, inflammation of the thyroid gland and kidneys may be present in women with autoimmune hepatitis.

Types of hepatitis

Viral

Most cases of acute hepatitis are due to viral infections:

• Hepatitis A
  
• Hepatitis B
• Hepatitis C
• Hepatitis B with D
• Hepatitis E
• 
  
• Hepatitis F virus
• Hepatitis G, or GBV-C
• In addition to the hepatitis viruses, other viruses can also cause hepatitis, including cytomegalovirus, Epstein-Barr virus, yellow fever, etc.

Other viral causes of hepatitis

Other viral infections can cause hepatitis (inflammation of the liver):

• Mumps virus
• Rubella virus
• Cytomegalovirus
• Epstein-Barr virus
• Other herpes viruses

Alcoholic hepatitis

Ethanol, mostly in alcoholic beverages, is a significant cause of hepatitis. Usually alcoholic hepatitis comes after a period of increased alcohol consumption. Alcoholic hepatitis is characterized by a variable constellation of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen ascites, and modest elevation of liver blood tests. Alcoholic hepatitis can vary from mild with only liver test elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time, and liver failure. Severe cases are characterized by either obtundation (dulled consciousness) or the combination of elevated bilirubin levels and prolonged prothrombin time; the mortality rate in both categories is 50% within 30 days of onset.

Alcoholic hepatitis is distinct from cirrhosis caused by long term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. 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.

Drug induced hepatitis

A large number of drugs can cause hepatitis:

• Allopurinol
• 
  
• Amitriptyline (antidepressant)
• Amiodarone (antiarrhythmic)
• Atomoxetine
• Azathioprine
• 
  
• Halothane (a specific type of anesthetic gas)
• Hormonal contraceptives
• Ibuprofen and indomethacin (NSAIDs)
• Isoniazid (INH), rifampicin, and pyrazinamide (tuberculosis-specific antibiotics)
• Ketoconazole (antifungal)
• Loratadine (antihistamine)
• Methotrexate (immune suppressant)
• Methyldopa (antihypertensive)
• Minocycline (tetracycline antibiotic)
• Nifedipine (antihypertensive)
• Nitrofurantoin (antibiotic)
• Phenytoin and valproic acid (antiepileptics)
• Troglitazone (antidiabetic, withdrawn in 2000 for causing hepatitis)
• Zidovudine (antiretroviral i.e. against HIV)
• Some herbs and nutritional supplements

The clinical course of drug-induced hepatitis is quite variable, depending on the drug and the patient's tendency to react to the drug. For example, halothane hepatitis can range from mild to fatal as can INH-induced hepatitis. Hormonal contraception can cause structural changes in the liver. Amiodarone hepatitis can be untreatable since the long half life of the drug (up to 60 days) means that there is no effective way to stop exposure to the drug. Statins can cause elevations of liver function blood tests normally without indicating an underlying hepatitis. Lastly, human variability is such that any drug can be a cause of hepatitis.

Other toxins that cause hepatitis

Toxins and drugs can cause hepatitis:

• Amatoxin-containing mushrooms, including the Death Cap (Amanita phalloides), the Destroying Angel (Amanita ocreata), and some species of Galerina. A portion of a single mushroom can be enough to be lethal (10 mg or less of α-amanitin).
• White phosphorus, an industrial toxin and war chemical.
• Paracetamol can cause hepatitis when taken in an overdose. The severity of liver damage may be limited by prompt administration of acetylcysteine.
• Carbon tetrachloride ("tetra", a dry cleaning agent), chloroform, and trichloroethylene, all chlorinated hydrocarbons, cause steatohepatitis (hepatitis with fatty liver).
• Cylindrospermopsin, a toxin from the cyanobacterium Cylindrospermopsis raciborskii and other cyanobacteria.

Metabolic disorders

Some metabolic disorders cause different forms of hepatitis. Hemochromatosis (due to iron accumulation) and Wilson's disease (copper accumulation) can cause liver inflammation and necrosis.

Obstructive

"Obstructive jaundice" is the term used to describe jaundice due to obstruction of the bile duct (by gallstones or external obstruction by cancer). If longstanding, it leads to destruction and inflammation of liver tissue.

Autoimmune

Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection; causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis.

Alpha 1-antitrypsin deficiency

In severe cases of alpha 1-antitrypsin deficiency (A1AD), the accumulated protein in the endoplasmic reticulum causes liver cell damage and inflammation.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the occurrence of fatty liver in people who have no history of alcohol use. It is most commonly associated with obesity. It is more common in women. Severe NAFLD leads to inflammation, a state referred to as non-alcoholic steatohepatitis (NASH), which on biopsy of the liver resembles alcoholic hepatitis.

The diagnosis depends on medical history, physical exam, blood tests, radiological imaging and sometimes a liver biopsy. The initial evaluation to identify the presence of fatty infiltration of the liver is medical imaging, including such ultrasound, computed tomography (CT), or magnetic resonance (MRI). However, imaging cannot readily identify inflammation in the liver. Therefore, the differentiation between steatosis and NASH often requires a liver biopsy. It can also be difficult to distinguish NASH from alcoholic hepatitis when the patient has a history of alcohol consumption. Sometimes in such cases a trial of abstinence from alcohol along with follow-up blood tests and a repeated liver biopsy are required.

NASH is becoming recognized as the most important cause of liver disease second only to hepatitis C in numbers of patients going on to cirrhosis.

Ischemic hepatitis

Ischemic hepatitis is caused by decreased circulation to the liver cells. Usually this is due to decreased blood pressure (or shock), leading to the equivalent term "shock liver". Patients with ischemic hepatitis are usually very ill due to the underlying cause of shock. Rarely, ischemic hepatitis can be caused by local problems with the blood vessels that supply oxygen to the liver (such as thrombosis, or clotting of the hepatic artery which partially supplies blood to liver cells). Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT), which may exceed 1000 U/L. It is rare that liver function will be affected by ischemic hepatitis.