HEPATITIS: DEFINITION: Hepatitis is an inflammation of the liver, which can be caused by a virus, a bacteria, and/or a toxic substance such as alcohol. For viral hepatitis there is usually a week or so of malaise, fatigue, aches, lack of appetite, and headache, followed by nausea and vomiting, dark urine, and jaundice. Hepatitis A is commonly aquired by the fecal-oral route, thus bad water is a common etiology. Hepatitis B and C are aquired by needle sticks and other types of blood transfer from person to person. Hepatitis D, E, and F and still under study. Alcoholic hepatitis is caused from drinking to much alcohol. Bacterial hepatitis is usually caused by a gall bladder infection, this problem is life threatening. Other causes of hepatitis can be by other problems of the liver such as cancer, parasites, etc. DIAGNOSING: Tests will determine which type of hepatitis you have: 1) Hepatitis B: This type of hepatitis is less contagious, but is often transmitted by needles. The length of the illness is longer, and the chance of long-term complications is greater. 2) Infectious hepatitis: More contagious, shorter time of illness (2-4 weeks). THERAPY: Close personal contacts may need to get gamma globulin shots if you have hepatitis A. There is no medical cure for viral hepatitis, though this problem is being worked on. While you are ill, you may receive medication to make you more comfortable. Do not drink, and don't take any drug or medication not approved by your doctor. Rest and try to eat a healthy diet. Many persons that get viral hepatitis, have the disease, it runs its course and the person gets better and over it. A few people get chronic hepatitis which has a poor outcome. IF PROBLEMS Call the doctor if vomiting or abdominal pain become severe. Liver failure is the serious consequence, once the liver stops functioning, a special diet is required, lactulose to decrease the ammonia level and continued therapy. Liver failure has a poor outcome as a general rule. HEPATITIS Background: Hepatitis is a general term which refers to inflammation of the liver. This inflammation can result from various infectious and non-infectious etiologies. Infectious etiologies include viral, bacterial, fungal and parasitic organisms. Non-infectious hepatitis may be caused by medications, toxins and autoimmune disorders. This discussion will focus on acute infectious hepatitis. Frequency: In the U.S.: In 1994, more than 44,000 cases of infectious hepatitis in the United States were reported to the Centers for Disease Control (CDC). These numbers grossly underestimate the actual number of cases of infectious hepatitis because the diagnosis is often missed and because many cases are never reported. The CDC estimates that the true number of cases to be 500,000-750,000 new cases per year. Mortality/Morbidity: Viral hepatitis induced liver disease accounts for 4000-5000 deaths per year. It is the leading cause of fulminant acute hepatic failure in the United States. CLINICAL History: The clinical presentation of infectious hepatitis may vary from person to person. Some patients may be entirely asymptomatic or only mildly symptomatic. Others may present with rapid onset of fulminant hepatic failure. The classic presentation of infectious hepatitis is described as involving four phases. The first phase is that of viral replication. Although patients are asymptomatic during this phase, laboratory studies demonstrate serologic and enzyme markers of hepatitis. The second phase is the prodromal phase. During this phase, patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias, malaise, fatigue, uriticaria, pruritis and some even develop an aversion to cigarette smoke. When seen by a health care provider during this phase, patients are often diagnosed as having gastroenteritis or a viral syndrome. During the third phase, also known as the icteric phase, patients may note darkening of the urine, followed by pale colored stools. In addition to the predominant gastrointestinal symptoms and malaise, patients become icteric and may develop right upper quadrant pain with hepatomegaly. Finally, during the fourth or convalescent phase, symptoms and icterus resolve and liver enzymes return to normal. Physical: The physical findings in patients with hepatitis may vary with the type of hepatitis and with time at presentation. Patients are often found to have low grade fever on exam. In addition, if they have experienced significant vomiting and anorexia, patients may show signs of dehydration such as tachycardia, dry mucus membranes, loss of skin turgor and delayed capillary refill. Patients in the icteric phase may be noted to have icterus of the sclera or mucus membranes or discoloration of the tympanic membranes. The skin may be jaundiced and may reveal macular, papular or urticarial rashes. In viral hepatitis, the liver may be tender and diffusely enlarged with a firm, sharp, smooth edge. If the liver is found to be nodular or if a mass is palpated, one should be suspicious of an abscess or tumor. Causes: The focus of this chapter will be on infectious hepatitis, as such, this section will discuss the etiology of this class of hepatitis. A brief discussion of drug-induced and autoimmune hepatitis is at the end of this chapter. Infectious hepatitis, viral: The majority of clinical cases of viral hepatitis are caused by 5 major hepatotropic viruses. These are Hepatitis A virus (HAV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), and Hepatitis E virus (HEV). It is suspected that a small percentage of cases of acute hepatitis may be caused by other viral agents that have yet to be identified. These agents have been referred to in the literature as F, G or non-ABCDE viruses. Hepatitis viruses A, B, C and D are the only four which are endemic to the United States. Hepatitis A virus Epidemiology: The hepatitis A virus is a picornavirus that is quite resistant to environmental factors such as temperature and certain chemicals. HAV is the predominant etiologic agent of viral hepatitis in the United States and is thought to account for 25-32% of new cases of hepatitis per year. In 1991, the CDC estimated that the actual number of new cases of Hepatitis A was approximately 136,000. Transmission: Hepatitis A virus is found in highest concentration in the feces of infected individuals. The greatest fecal viral load tends to occur near the end of the incubation period of HAV. Most commonly, the virus is spread person-to-person via the fecal-oral route. Contaminated water and food, to include shellfish collected from sewage contaminated water, have also resulted in epidemics of HAV. Finally, the virus can also be spread via infected serum. Infection with HAV is known to occur throughout the world. However, risk of infection is greatest in poorly developed countries, areas of low socioeconomic status, and areas without sufficient sanitation. Infection rates are also higher in settings where fecal-oral spread is likely to occur, such as day-care centers. Other groups at high risk for HAV infection include international travelers, users of injection drugs, military personnel stationed abroad, homosexual men and close contacts of infected individuals. Clinical course: The incubation period of HAV is 2-7 weeks, with the average being about 28 days. Clinical symptoms then develop, often presenting similar to gastroenteritis or a viral respiratory infection. The most common signs and symptoms are fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia and rash. Hepatitis A infection is usually a mild, self-limited disease. Chronic infection with HAV does not occur and infection with the virus confers life-long immunity to HAV. Morbidity and mortality: Although HAV usually causes mild disease, the older the patient, the more severe their disease is likely to be. While icteric disease occurs in less than 10% of children under the age of six, it occurs in 40-50% of older children and in 70-80% of adults. The overall mortality rate for Hepatitis A infection is approximately 0.01%. Children less than 5 years of age and adults greater than 50 years of age, however, have higher case-fatality rates. Hepatitis B virus Epidemiology: A major cause of infectious hepatitis seen worldwide, Hepatitis B virus belongs to the class of hepadna viruses. HBV is responsible for about 43% of acute viral hepatitis cases in the United States. For the past several years in the United States, there have been an estimated 200,000-300,000 cases of HBV infections occuring each year, with adults and adolescents accounting for the majority of cases. The incidence of childhood HBV infection is not well established because more than 90% of HBV infections in this age group are asymptomatic. Transmission: The major reservoir of HBV in the United States is the 1.25 million people with chronic HBV infection. In this group, those with hepatitis B e antigen (HBeAg) in their serum tend to have higher virus titers and, thus, greater infectivity. HBV is transmitted parenterally, most often by mucus membrane exposure or percutaneous exposure to infectious bodily fluids. Saliva, serum and semen have all been determined to be infectious. Percutaneous exposures that have led to the transmission of HBV include transfusion of blood or blood products, needlesticks or wounds caused by other sharp implements incurred by hospital workers, injection drug use with shared needles and hemodialysis. Another significant mode of transmission is perinatal transmission. The greatest risk of perinatal transmission occurs in infants of women who are HBeAg-positive. By 6 months of age, these children have a 70-90% risk of infection and, of those, about 90% will go on to develop chronic infection with HBV. For infants born to women who are HBeAg-negative, the risk of infection is approximately 10-40 %, with a chronic infection rate of 40-70%. Even if transmission does not occur in the perinatal period, these children still have a significant risk of developing infection during early childhood. High risk groups for infection with HBV include intravenous drug users, persons born in endemic areas and homosexually active men. Other groups at risk are health care workers with exposure to infected blood or bodily fluids, recipients of multiple blood transfusions, hemodialysis patients, heterosexual persons with multiple partners or a history of sexually transmitted disease, institutionalized persons including prisoners or the developmentally disabled and household contacts or sexual partners of HBV carriers. Disease course: The incubation period for HBV varies from 30-180 days, with the average time being about 75 days. Patients then enter the prodromal or pre-icteric phase, developing gradual onset of anorexia, malaise and fatigue. During this phase, as the liver becomes inflamed, liver enzymes start to elevate and the patient may experience right upper quadrant pain. Fifteen percent of patients develop an illness resembling serum sickness. These patients may experience fever, arthritis, arthralgias or an urticarial rash. As patients progress to the icteric phase, the liver becomes tender and jaundice develops. They may note that their urine has become dark and that their stools have lightened in color. Other symptoms seen in this stage include nausea, vomiting and pruritis. From this point on, patients may have quite a variable course. Some experience fairly rapid improvement in their symptoms, while others go on to a prolonged disease course with slow resolution. Still others may have symptoms which periodically improve only to later exacerbate. Finally, there is an unfortunate subset of patients who suffer rapid progression of their disease to the point of fulminant hepatic failure. This may occur over days to weeks. Complications: One of the major complications of HBV infection is the development of a chronic carrier state. These patients are at risk of later developing chronic active hepatitis, cirrhosis of the liver and eventual hepatocellular cancer. The risk of developing chronic HBV infection is greatest for those who are infected at an early age. While 90% of those infected at birth develop chronic HBV, only 5-10% of older children or adults go on to chronic infection. The risk of chronic infection is higher as well in patients who are immunocompromised. Patients with chronic HBV infection have a significantly increased risk of developing hepatocellular cancer. In fact, hepatocellular cancer is the leading cause of cancer-related deaths in areas where HBV is endemic. Another major complication of HBV infection is the development of fulminant hepatic failure. About 0.5-1% of HBV infected patients will progress to fulminant hepatic failure. The case fatality rate for these patients is around 80%. Hepatitis C virus Epidemiology: Hepatitis C is a single stranded RNA virus that is the most frequent cause of parenteral non-A, non-B hepatitis worldwide. Before the newer universal screening measures, HCV had accounted for 90% of cases of post-transfusion hepatitis. HCV is responsible for about 20-40% of hepatitis cases in the United States and the CDC estimates that there are 150,000 HCV infections annually. The highest rates of disease prevalence are found in patients with hemophilia and in injection drug users. Transmission: HCV can be transmitted parenterally, perinatally and sexually. HCV is most reliably transmitted through transfusion of infected blood or blood products, transplantation of organs from infected donors and sharing contaminated needles among intravenous drug users. Needlestick injuries among health care workers place them at significant risk of infection. The incidence of HCV infection in health care workers with history of needlestick exposure to infected blood is as high as 10%. Even more concerning, there is a 0.4-1% chance of developing irreversible liver injury from a needlestick in this setting. Disease Course: The incubation period for HCV is 15-150 days, with symptoms developing anywhere from 5-12 weeks post exposure. During acute infection with HCV, symptoms may be similar to those with hepatitis B infection. In up to 80% of cases, however, patients are aymptomatic and do not develop icterus. Complications: Acute infection with HCV can cause fulminant hepatic failure and has been associated with aplastic anemia. Approximately 50-60% of patients become chronically infected with HCV. Of those with chronic HCV, 29-76% later develop chronic active hepatitis or cirrhosis. In fact, HCV is a leading cause of chronic hepatitis and cirrhosis worldwide. Finally, HCV is also strongly linked to the development of hepatocellular cancer. Hepatitis D virus Epidemiology: Hepatitis D is an incomplete virus that requires the presence of HBV in order to replicate. HDV infection is found only in patients who are Hepatitis B surface antigen positive. Patients may acquire HDV as a coinfection (at the same time that they contract HBV) or the HDV can superinfect patients who are chronic HBV carriers. Although it is not a reportable disease, the CDC estimates that HDV results in 7500 infections each year. Approximately 4% of cases of acute hepatitis B are thought to involve coinfection with HDV. Transmission: The modes of transmission of HDV are similar to those for HBV, although perinatal transmission is rare and has not been documented in the United States. Disease course: The incubation period of HDV is approximately 35 days. Patients who are coinfected with HBV and HDV tend to have a more severe disease course than those infected with HBV alone. As many as 1/3 of those with coinfection go on to develop fulminant hepatitis. Chronic HBVcarriers who are superinfected with HDV usually develop chronic HDV infection as well. Chronic infection with both HBV and HDV often leads to rapidly progressive subacute or chronic hepatitis, resulting in a more rapid progression to cirrhosis. Over the long term, as many as 70-80% of these patients are found to have evidence of chronic liver disease with cirrhosis, as compared to only 15-30% of patients with chronic HBV alone. Hepatitis E virus Hepatitis E virus is also referred to as enterically transmitted Non-A, Non-B hepatitis. Seen mainly in developing countries, Hepatitis E transmission has not been documented in the United States. The documented cases diagnosed in the U.S. have all been in persons traveling from countries where HEV is endemic. Transmission: Hepatitis E is transmitted primarily by the fecal-oral route with fecally contaminated water being the most common means of transmission. It is not known whether person-to-person contact results in transmission. Disease course: Hepatitis E virus usually causes an acute self-limited disease. There is no known chronic HEV infection. In pregnant women, however, HEV infection has a case fatality rate of 15-20%. Viral hepatitis, other: There are other proposed agents of viral hepatitis currently being explored. It is suspected that there may be another form of parenterally transmitted hepatitis, now referred to as Non-ABCDE hepatitis. Hepatitis F has been proposed as another enterically transmitted hepatitis virus. Hepatitis G is thought to be a new form of severe, sporadic hepatitis. Other known viruses can cause inflammation of the liver as well. These include cytomegalovirus, Epstein-Barr virus, Herpes Simplex and Varicella Zoster. Infectious hepatitis, non-viral: Infectious hepatitis can be caused by hepatic abscesses as well. These are found more often in patients with chronic illness. The two general categories of abscess are amebic and pyogenic. Amebic abscesses are caused by Entamoeba histolytica and occur most commonly in developing countries. Pyogenic abscesses tend to affect those at the extremes of age. In neonates, sepsis and catheterization of the umbilical vein may result in abscesses caused by gram positive aerobic cocci. In adults, biliary disease can result in pyogenic abscess formation and in the elderly, malignancy is the most common underlying disease. Gram negative rods are the typical causative organisms in adults. The mortality rate of pyogenic abscesses is almost 40%. DIFFERENTIALS Cholecystitis and Biliary Colic Cholelithiasis Gastroenteritis Other Problems to be Considered: Liver abscess Drug - induced hepatitis Autoimmune hepatitis WORKUP Lab Studies: For the non-icteric patient with suspected viral hepatitis, a simple screening test is to check the urine for presence of bilirubin. Alternatively, a liver enzyme panel could be obtained, however, the clinician should remember that this is generally a costly test. Bedside fingerstick glucose testing is important to evaluate for hypoglycemia in patients with an altered or a questionable mental status. Further testing is described below. Serum bilirubin - Total and Fractionated - In infectious hepatitis, total bilirubin may be elevated. Bilirubin levels greater than 30 mg/dl indicate more severe disease. Alkaline phosphatase - This is usually normal, but when elevated, it is usually no higher than 2 times normal level. If the alkaline phosphatase is significantly elevated, consider abscess or biliary obstruction. Prothrombin time - Prolongation of the prothrombin time is a grave finding, indicating impaired synthetic function of the liver. Blood urea nitrogen and serum creatinine - Draw to look for evidence of renal impairment. Decreased renal function suggests fulminant hepatic disease. Serum ammonia - In patients with altered mental status or other evidence of hepatic encephalopathy, a serum ammonia level should be measured. Antibody to hepatitis A virus (IgM anti-HAV) - Detecting the presence of IgM anti-HAV in the serum is the standard for diagnosing acute infection with HAV. Hepatitis B core antibody (IgM anti-HBc) - In order to make the diagnosis of acute HBV infection, the physician needs to determine the presence of IgM anti-HBc in the serum. Hepatitis B surface antigen (HBsAg) - HBsAg may be present in acute infection or in patients who are chronic carriers. Its presence in a patient with symptoms of acute hepatitis strongly suggests acute HBV infection but does not rule out chronic HBV with acute superinfection by another hepatitis virus. Antibody to HCV (Anti-HCV) - With older assays, this antibody may not be detectable until 16 weeks after initial infection. Newer assays are on the horizon. In the future, assays which detect the presence of HCV RNA within 3 weeks of infection may become commercially available. There are assays to detect IgM antibody to HDV but these do not need to be sent routinely on all patients with suspected hepatitis. Imaging Studies: No specific imaging studies are required to make the diagnosis of hepatitis. If your differential diagnosis favors gallbladder disease, biliary obstruction or liver abscess then the appropriate diagnostic studies should be obtained. These might include ultrasound or computed tomography. TREATMENT Emergency Department Care: Viral hepatitis: There is no specific ED treatment other than supportive care including intravenous rehydration. A liver abscess will require intravenous antibiotic therapy directed toward the most likely pathogens and consultation for possible surgical or percutaneous drainage. FOLLOW-UP Further Inpatient Care: Patients with hepatitis should be admitted if they are showing any signs or symptoms suggestive of severe complications. Those with altered mental status, agitation, behavior or personality changes or changes in their sleep-wake cycle require admission and an evaluation for hepatic encephalopathy. Other admission criteria which are suggestive of severe disease include a prothrombin time prolonged greater than 3 seconds, bilirubin greater than 30mg/dl and hypoglycemia. Patients with intractable vomiting, significant electrolyte and fluid disturbances, greater than 50 years of age, significant comorbid illness or who are immunocompromised also require admission. Further Outpatient Care: Most patients with viral hepatitis can be followed as outpatients. Ensure that the patient will be able to maintain adequate hydration and obtain close follow-up care with their primary care physician. Deterrence: Hepatitis A - Improved sanitation, strict personal hygiene and handwashing may all help to prevent transmission of HAV. There is an inactivated viral vaccine that has proven highly effective in preventing infection with HAV when given pre-exposure. Active immunization is recommended for health care workers, daycare personnel and travelers to endemic areas. Passive immunization with immune globulin (dose 0.02ml/kg) can protect against clinical illness for those persons exposed to HAV. It is most effective if given within 48 hours of exposure but may be helpful when given as far as 2 weeks into the incubation period. Hepatitis B - Infection can be prevented by active immunization with the three-dose recombinant DNA HBV vaccine. Use of this vaccine has proven very successful in preventing infection among those at risk for HBV infection because of occupational exposure. It is further recommended that this vaccine be given to all children as part of the usual immunization schedule, as well as to infants born to mothers who are potentially infectious. Unimmunized persons who are close contacts of patients with acute HBV infection or who suffer percutaneous exposure to HBV and infants born to potentially infectious mothers should receive passive immunization with the hepatitis B immune globulin in addition to active immunization. Combining the active and passive immunization in these settings is 80% to 95% effective in preventing transmission of HBV. Hepatitis C - There is no vaccine against HCV and immune globulin has not been proven to prevent transmission. In fact, immune globulin administration has been associated with HCV. At the present time, the major means of preventing transmission is to prevent infected blood, organs and semen from entering the donor pool. Hepatitis D - Since hepatitis D can only infect patients when hepatitis B is present, transmission of this disease can be decreased by effectively immunizing patients against hepatitis B. Unfortunately, at this time, there is no known means of preventing HDV superinfection in patients with chronic HBV. Hepatitis E - There is no vaccine for prevention of hepatitis E and administration of immune globulin does not prevent development of clinical disease. Patient Education: As it is unlikely that the specific etiologic virus will be known at time of discharge from the ED, patients with infectious hepatitis should be referred to their primary care providers for further counseling specific to their disease. Patients need to understand the importance of follow-up in order to monitor for evidence of disease progression or development of complications. In general, patients should be advised to exercise meticulous personal hygiene to include strict handwashing. In addition, they should be instructed not to share any articles with potential for contamination with blood, semen or saliva to include needles, toothbrushes or razors. Food handlers who are suspected of having HAV should be told not to return to work until their primary care physician can confirm that they are no longer shedding virus. MISCELLANEOUS Special Concerns: Pregnancy: In general, none of the hepatitis viruses are known to be teratogenic. Except in the case of Hepatitis E, the disease courses of the various hepatitis viruses are no different in pregnancy. Treatment is usually supportive care. Patients with significant vomiting or dehydration may require admission for hydration as well as monitoring for fetal well being and preterm uterine irritability. Non-immunized pregnant patients who are exposed to HAV or HBV should receive active and passive immunization with the appropriate immune globulin and viral vaccine as described earlier. Immune globulin, Hepatitis B immune globulin, HAV vaccine and HBV vaccine are all approved for use during pregnancy at this time. Hepatitis A virus: Hepatitis A has an incidence of less than 1 in 1000 in pregnancy. HAV is not transmitted to the fetus in utero but may be transmitted to the neonate during delivery or during the post-partum period (fecal-oral route). Infants born to women infected with HAV during the third trimester should receive post-exposure prophylaxis with immunoglobulin. Hepatitis B virus: Acute infection with HBV occurs at a rate of 1-2 per 1000 pregnancies. In addition, 0.5% to 1.5% of pregnant women are chronic carriers of HBV. There is no evidence of transplacental infection; perinatal infection of the neonate usually occurs during delivery. Infants born to mothers who are chronic carriers of HBV or who acquire acute HBV infection during the third trimester should receive active and passive immunization. When these neonates receive hepatitis B vaccine and hepatitis B immune globulin within 12 hours of delivery, the rate of vertical transmission is decreased such that less than 5% of exposed neonates will go on to become chronic carriers. Hepatitis C virus: The most common risk factor for HCV infection in pregnancy is history of substance abuse. Vertical transmission does occur but the exact frequency of this occurence is unknown. Hepatitis D virus: Perinatal transmission rarely occurs. Hepatitis E virus: The disease course of HEV during pregancy may be more severe. HEV in pregnancy has a high case fatality rate, especially when the disease is contracted during the second or third trimester. Perinatal transmission does occur but with undetermined frequency. When vertical transmission of HEV does occur it is associated with significant perinatal morbidity and mortality. Drug-induced hepatitis: There are a large number of prescription medicines, drugs and chemical agents known to cause hepatotoxicity. Some agents cause hepatic damage directly, while others induce an autoimmune response against the liver. Damage can ocurr acutely or from chronic exposure. Hepatitis induced by medication accounts for up to 5% of hospitalizations for hepatitis in the United States. Moreover, drug-induced hepatitis follows viral hepatitis as a leading cause of fulminant hepatic failure in the United States. Several drugs of abuse are known to cause hepatic injury. These include cocaine, methylenedioxymetamphetamine (ecstacy), toluene, trichloroethylene, phencyclidine and ethanol. Patients hospitalized with hepatitis induced by ethanol have a reported mortality rate of 20-65%. Herbal medicines and toxic plants have also been implicated in causing hepatitis. Finally, occupational exposure to a variety of industrial agents can produce liver injury. Acute hepatitis can result from a single large exposure to one of the hepatotoxic agents. These substances may be ingested, inhaled as toxic fumes or absorbed through the skin. In general, once significant exposure has occurred, there is a three phase clinical syndrome of acute hepatic injury described. During phase 1, patients develop gastrointestinal symptoms such a nausea, vomiting, diarrhea and abdominal pain. They may also exhibit delerium, seizures or coma, representing associated central nervous system toxicity. Between 24-48 hours after exposure, patients enter phase 2, where they often experience resolution of their symptoms. Phase 3 occurs 48-72 hours post-exposure with the development of fulminant hepatic failure, often accompanied by renal failure. Some of these patients may deteriorate to the point that they face death or require emergent liver transplantation. Autoimmune hepatitis: Autoimmune hepatitis is a progressive inflammatory disease of the liver. This disease occurs more commonly in young women and girls. The etiology is not known but is believed that a certain environmental trigger incites an autoimmune response directed against the liver. These triggers might be viruses, chemicals or other unknown agents. The resulting chronic hepatitis eventually leads to fibrosis and cirrhosis. Autoimmune hepatitis has also been associated with progression to primary hepatocellular carcinoma, but not with the same frequency as viral hepatitis. As with other forms of hepatitis, the clinical presentation of autoimmune hepatitis can be quite varied. Patients may be asymptomatic or they may present with insidious onset of constitutional symptoms and jaundice. Occasionally, patients may develop acute onset of symptoms, significant jaundice and elevated transaminases, mimicking a severe viral hepatitis. Patients with autoimmune hepatitis have circulating autoantibodies in their serum and often have elevated serum globulins, gamma globulins in particular. Other autoimmune diseases which may affect these patients include Grave's disease, idiopathic thrombocytopenic purpura, pulmonary fibrosis, vitiligo, ulcerative colitis, glomerulonephritis, insulin dependent diabetes mellitus, and myasthenia gravis.