Causes of<unk>  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<unk>  involve genetic predispositions and tend to affect characteristic populations. Infectious Viral<unk>  Viral<unk>  is the most common type of<unk>  worldwide, especially in Asia and Africa. Viral<unk>  is caused by five different viruses<unk>  A, B, C, D, and E).<unk>  A and<unk>  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<unk> .<unk>  B,<unk>  C, and<unk>  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. However contrary to myths, kissing,<unk> aring 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<unk>  because saliva and blood droplets are often carried through the water and blood-borne illnesses spread quickly in unsanitary settings.<unk>  B and C can present either acutely or chronically.<unk>  D is a defective virus that requires<unk>  B to replicate and is only found with<unk>  B co-infection. In adults,<unk>  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. However, infection in infants and children frequently leads to chronic infection. Unlike<unk>  B, most cases of<unk>  C lead to chronic infection.<unk>  C is the second most common cause of cirrhosis in the US (second to alcoholic<unk> . In the 1970s and 1980s, blood transfusions were a major factor in spreading<unk>  C virus. Since widespread screening of blood products for<unk>  C began in 1992, the risk of acquiring<unk>  C from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently. Parasitic<unk>  Echinococcus granulosus Parasites can also infect the liver and activate the immune response, resulting in symptoms of acute<unk>  with increased serum IgE (though chronic<unk>  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<unk>  with distinct liver abscesses. Of the worms, the cestode Echinococcus granulosus, also known as the dog tapeworm, infects the liver and forms characteristic<unk> atic hydatid cysts. The liver flukes Fasciola<unk> atica and Clonorchis sinensis live in the bile ducts and cause progressive<unk>  and liver fibrosis. Bacterial<unk>  Bacterial infection of the liver commonly results in pyogenic liver abscesses, acute<unk> , 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<unk>  is caused by Neisseria meningitidis, Neisseria gonorrhoeae, Bartonella henselae, Borrelia burgdorferi, salmonella species, brucella species and campylobacter species. Chronic or granulomatous<unk>  is seen with infection from mycobacteria species, Tropheryma whipplei, Treponema pallidum, Coxiella burnetii, and rickettsia species. Metabolic Alcoholic<unk>  Excessive alcohol consumption is a significant cause of<unk>  and is the most common cause of cirrhosis in the U.S. Alcoholic<unk>  is within the spectrum of alcoholic liver disease. This ranges in order of severity and reversibility from alcoholic steatosis (least severe, most reversible), alcoholic<unk> , cirrhosis, and liver cancer (most severe, least reversible).<unk>  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<unk>  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<unk>  (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). Alcoholic<unk>  can vary from asymptomatic<unk> atomegaly (enlarged liver) to symptoms of acute or chronic<unk>  to liver failure. Toxic and drug-induced<unk>  Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause<unk> . The spectrum of drug-induced liver injury varies from acute<unk>  to chronic<unk>  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 among individuals. 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<unk> ; these are the most common causes of drug-induced<unk>  in Korea. The United-States-based Drug Induced Liver Injury Network linked more than 16% of cases of<unk> atotoxicity to herbal and dietary supplements. In the United States, herbal and dietary supplements – unlike pharmaceutical drugs – are unregulated by the Food and Drug Administration. However, the National Institutes of Health maintains the LiverTox database for consumers to track all known prescription and non-prescription compounds associated with liver injury. Exposure to other<unk> atotoxins can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. The industrial toxin carbon tetrachloride and the wild mushroom Amanita phalloides are other known<unk> atotoxins. Non-alcoholic fatty liver disease Non-alcoholic<unk>  is within the spectrum of non-alcoholic liver disease (NALD), which ranges in severity and reversibility from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) to cirrhosis to liver cancer, similar to the spectrum of alcoholic liver disease. Non-alcoholic liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with metabolic syndrome, obesity, insulin resistance and diabetes, and hypertriglyceridemia. Over time, non-alcoholic fatty liver disease can progress to non-alcoholic steatohepatitis, which additionally involves liver cell death, liver inflammation and possible fibrosis. Factors accelerating progression from NAFLD to NASH are obesity, older age, non-African American ethnicity, female gender, diabetes mellitus, hypertension, higher ALT or AST level, higher AST/ALT ratio, low platelet count, and an ultrasound steatosis score. In the early stages (as with NAFLD and early NASH), most patients are asymptomatic or have mild right upper quadrant pain, and diagnosis is suspected on the basis of abnormal liver function tests. As the disease progresses, symptoms typical of chronic<unk>  may develop. While imaging can<unk> ow fatty liver, only liver biopsy can demonstrate inflammation and fibrosis characteristic of NASH. 9 to 25% of patients with NASH develop cirrhosis. NASH is recognized as the third most common cause of liver disease in the United States. Autoimmune Autoimmune<unk>  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 involved in the immune response. As in other autoimmune diseases, circulating auto-antibodies may be present and are helpful in diagnosis. Auto-antibodies found in patients with autoimmune<unk>  include the sensitive but less specific anti-nuclear antibody (ANA), smooth muscle antibody (SMA), and atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Other autoantibodies that are less common but more specific to autoimmune<unk>  are the antibodies against liver kidney microsome 1 (LKM1) and soluble liver antigen (SLA). Autoimmune<unk>  can also be triggered by drugs (such as nitrofurantoin, hydralazine, and methyldopa), after liver transplant, or by viruses (such as<unk>  A, Epstein-Barr virus, or measles). Autoimmune<unk>  can present anywhere within the spectrum from asymptomatic to acute or chronic<unk>  to fulminant liver failure. Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests. Some studies<unk> ow between 25% and 75% of cases present with signs and symptoms of acute<unk> . As with other autoimmune diseases, autoimmune<unk>  usually affects young females (though it can affect patients of either sex of any age), and patients can exhibit classic signs and symptoms of autoimmunity such as fatigue, anemia, anorexia, amenorrhea, acne, arthritis, pleurisy, thyroiditis, ulcerative colitis, nephritis, and maculopapular rash. Autoimmune<unk>  increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease. Many people with autoimmune<unk>  have other autoimmune diseases. Autoimmune<unk>  is distinct from the
Hepatitis
Cholecystitis
Viral hepatitis
Alcoholic hepatitis
Fatty liver disease
Alcoholic liver disease
Cirrhosis
Cholestasis