hepatitis hepatitis hepatitis is inflammation of the liver tissue. some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer. hepatitisalcoholic hepatitis as seen with a microscope, showing fatty changes (white circles), remnants of dead liver cells, and mallory bodies (twisted-rope shaped inclusions within some liver cells). (h&e stain)specialtyinfectious disease, gastroenterology, hepatologysymptomsyellowish skin, poor appetite, abdominal paincomplicationsscarring of the liver, liver failure, liver cancerdurationshort term or long termcausesviruses, alcohol, toxins, autoimmunepreventionvaccination (for viral hepatitis), avoiding excessive alcoholtreatmentmedication, liver transplantfrequency> 500 million casesdeaths> one million a year hepatitis is most commonly caused by the virus hepatovirus a, b, c, d, and e. other viruses can also cause liver inflammation, including cytomegalovirus, epstein–barr virus, and yellow fever virus. other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (nash). hepatitis a and e are mainly spread by contaminated food and water. hepatitis b is mainly sexually transmitted, but may also be passed from mother to baby during pregnancy or childbirth and spread through infected blood. hepatitis c is commonly spread through infected blood such as may occur during needle sharing by intravenous drug users. hepatitis d can only infect people already infected with hepatitis b. hepatitis a, b, and d are preventable with immunization. medications may be used to treat chronic viral hepatitis. antiviral medications are recommended in all with chronic hepatitis c, except those with conditions that limit their life expectancy. there is no specific treatment for nash; physical activity, a healthy diet, and weight loss are recommended. autoimmune hepatitis may be treated with medications to suppress the immune system. a liver transplant may be an option in both acute and chronic liver failure. worldwide in 2015, hepatitis a occurred in about 114 million people, chronic hepatitis b affected about 343 million people and chronic hepatitis c about 142 million people. in the united states, nash affects about 11 million people and alcoholic hepatitis affects about 5 million people. hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer. in the united states, hepatitis a is estimated to occur in about 2,500 people a year and results in about 75 deaths. the word is derived from the greek hêpar (ἧπαρ), meaning "liver", and -itis (-ῖτις), meaning "inflammation". signs and symptoms jaundiced eyes hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. the acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ. acute hepatitis acute viral hepatitis follows three distinct phases: the initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. these include fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. fever, when present, is most common in cases of hepatitis a and e. late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools. yellowing of the skin and whites of the eyes follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. the non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an enlarged liver and right upper abdominal pain or discomfort. 10–20% of people will also experience an enlarged spleen, while some people will also experience a mild unintentional weight loss. the recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. all cases of hepatitis a and e are expected to fully resolve after 1–2 months. most hepatitis b cases are also self-limiting and will resolve in 3–4 months. few cases of hepatitis c will resolve completely. both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity. fulminant hepatitis fulminant hepatitis, or massive hepatic cell death, is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis b, d, and e, in addition to drug-induced and autoimmune hepatitis. the complication more frequently occurs in instances of hepatitis b and d co-infection at a rate of 2–20% and in pregnant women with hepatitis e at rate of 15–20% of cases. in addition to the signs of acute hepatitis, people can also demonstrate signs of coagulopathy (abnormal coagulation studies with easy bruising and bleeding) and encephalopathy (confusion, disorientation, and sleepiness). mortality due to fulminant hepatitis is typically the result of various complications including cerebral edema, gastrointestinal bleeding, sepsis, respiratory failure, or kidney failure. chronic hepatitis acute cases of hepatitis are seen to be resolved well within a six-month period. when hepatitis is continued for more than six months it is termed chronic hepatitis. chronic hepatitis is often asymptomatic early in its course and is detected only by liver laboratory studies for screening purposes or to evaluate non-specific symptoms. as the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis, including fatigue, nausea, vomiting, poor appetite, and joint pain. jaundice can occur as well, but much later in the disease process and is typically a sign of advanced disease. chronic hepatitis interferes with hormonal functions of the liver which can result in acne, hirsutism (abnormal hair growth), and amenorrhea (lack of menstrual period) in women. extensive damage and scarring of the liver over time defines cirrhosis, a condition in which the liver's ability to function is permanently impeded. this results in jaundice, weight loss, coagulopathy, ascites (abdominal fluid collection), and peripheral edema (leg swelling). cirrhosis can lead to other life-threatening complications such as hepatic encephalopathy, esophageal varices, hepatorenal syndrome, and liver cancer. causes causes of hepatitis can be divided into the following major categories: infectious, metabolic, ischemic, autoimmune, genetic, and other. infectious agents include viruses, bacteria, and parasites. metabolic causes include prescription medications, toxins (most notably alcohol), and non-alcoholic fatty liver disease. autoimmune and genetic causes of hepatitis involve genetic predispositions and tend to affect characteristic populations. viral hepatitis main article: viral hepatitis viral hepatitis is the most common type of hepatitis worldwide, especially in asia and africa. viral hepatitis is caused by five different viruses (hepatitis a, b, c, d, and e). hepatitis a and hepatitis e behave similarly: they are both transmitted by the fecal–oral route, are more common in developing countries, and are self-limiting illnesses that do not lead to chronic hepatitis. hepatitis b, hepatitis c, and hepatitis d are transmitted when blood or mucous membranes are exposed to infected blood and body fluids, such as semen and vaginal secretions. viral particles have also been found in saliva and breastmilk. kissing, sharing utensils, and breastfeeding do not lead to transmission unless these fluids are introduced into open sores or cuts. many families who do not have safe drinking water or live in unhygienic homes have contracted hepatitis because saliva and blood droplets are often carried through the water and blood-borne illnesses spread quickly in unsanitary settings. hepatitis b and c can present either acutely or chronically. hepatitis d is a defective virus that requires hepatitis b to replicate and is only found with hepatitis b co-infection. in adults, hepatitis b infection is most commonly self-limiting, with less than 5% progressing to chronic state, and 20 to 30% of those chronically infected developing cirrhosis or liver cancer. infection in infants and children frequently leads to chronic infection. unlike hepatitis b, most cases of hepatitis c lead to chronic infection. hepatitis c is the second most common cause of cirrhosis in the us (second to alcoholic hepatitis). in the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis c virus. since widespread screening of blood products for hepatitis c began in 1992, the risk of acquiring hepatitis c from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently. parasitic hepatitis echinococcus granulosus parasites can also infect the liver and activate the immune response, resulting in symptoms of acute hepatitis with increased serum ige (though chronic hepatitis is possible with chronic infections). of the protozoans, trypanosoma cruzi, leishmania species, and the malaria-causing plasmodium species all can cause liver inflammation. another protozoan, entamoeba histolytica, causes hepatitis with distinct liver abscesses. of the worms, the cestode echinococcus granulosus, also known as the dog tapeworm, infects the liver and forms characteristic hepatic hydatid cysts. the liver flukes fasciola hepatica and clonorchis sinensis live in the bile ducts and cause progressive hepatitis and liver fibrosis. bacterial hepatitis bacterial infection of the liver commonly results in pyogenic liver abscesses, acute hepatitis, or granulomatous (or chronic) liver disease. pyogenic abscesses commonly involve enteric bacteria such as escherichia coli and klebsiella pneumoniae and are composed of multiple bacteria up to 50% of the time. acute hepatitis is caused by neisseria meningitidis, neisseria gonorrhoeae, bartonella henselae, borrelia burgdorferi, salmonella species, brucella species and campylobacter species. chronic or granulomatous hepatitis is seen with infection from mycobacteria species, tropheryma whipplei, treponema pallidum, coxiella burnetii, and rickettsia species. alcoholic hepatitis main article: alcoholic hepatitis excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the u.s. alcoholic hepatitis is within the spectrum of alcoholic liver disease. this ranges in order of severity and reversibility from alcoholic steatosis (least severe, most reversible), alcoholic hepatitis, cirrhosis, and liver cancer (most severe, least reversible). hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics. the most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake. long-term 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 (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). alcoholic hepatitis can vary from asymptomatic hepatomegaly (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure. toxic and drug-induced hepatitis many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis. the spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disruption of cell metabolism, and causing structural changes. some drugs such as paracetamol exhibit predictable dose-dependent liver damage while others such as isoniazid cause idiosyncratic and unpredictable reactions that vary by person. there are wide variations in the mechanisms of liver injury and latency period from exposure to development of clinical illness. many types of drugs can cause liver injury, including the analgesic paracetamol; antibiotics such as isoniazid, nitrofurantoin, amoxicillin-clavulanate, erythromycin, and trimethoprim-sulfamethoxazole; anticonvulsants such as valproate and phenytoin; cholesterol-lowering statins; steroids such as oral contraceptives and anabolic steroids; and highly active anti-retroviral therapy used in the treatment of hiv/aids. of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and paracetamol toxicity the most common cause of acute liver failure in the united states and europe. herbal remedies and dietary supplements are another important cause of hepatitis; these are the most common causes of drug-induced hepatitis in korea. the united-states-based drug induced liver injury network linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements. in the united states, herbal and dietary supplements – unlike pharmaceutical drugs – are unregulated by the food and drug administration. the national institutes of health maintains the livertox archived 2019-07-24 at the wayback machine database