A middle-aged woman with Sjögren's-like symptoms (absence of lacrimation, dry mouth), with hyperbilirubinemia, jaundice and hepatomegaly, makes us think of primary biliary cirrhosis. To diagnose it we will use antimitochondrial antibodies (AMA IgG). Therefore, it would be answer 1.

A middle-aged woman with Sjögren's-like symptoms (absence of lacrimation, dry mouth), with hyperbilirubinemia, jaundice and hepatomegaly, makes us think of primary biliary cirrhosis. To diagnose it we will use antimitochondrial antibodies (AMA IgG). Therefore, it would be [HIDDEN].

A 52-year-old woman consults for having noticed during the previous week a yellowish discoloration of the conjunctivae. She does not refer to risky sexual behavior or epidemiological history of risk of viral hepatitis. She does not consume alcohol or hepatotoxic drugs. She reports a one-year history of generalized pruritus, asthenia, dry mouth and absence of lacrimation with no known cause. Rest of the anamnesis without pathological data. Physical examination showed scratching lesions conjunctival jaundice and non-painful hepatomegaly. The patient brings a blood test carried out in his company with the following pathological results: total bilirubin 3 mg/dl alkaline phosphatase 400 UI sedimentation rate 40 mm at the first hour. Indicate which would be the best recommendation to establish the etiological diagnosis of the patient's condition:

[Acute hepatitis secondary to hepatitis E. Report of two cases from a population of high socioeconomic level Lima].

We describe two cases with acute hepatitis of patients who live at Lima, Peru and have a high socio-economic status. The first case, is a 58 years old female with asthenia, jaundice, coluria and pruritus. The physical exam revealed jaundice and laboratory exams revealed transaminasemia (AST= 1754, ALT= 2680) and hyperbilirubinemia (total bilirubin= 7.98, direct bilirubin=7.03). Furthering serologic tests, revealed a positive test for anti-Hepatitis E virus IgM and IgG. All the symptoms were remitted by the 3rd week of disease. The second case described, is a 64 years old female with asthenia, hyporexia and abdominal pain, without jaundice. The physical exam was normal and initial laboratory tests revealed an AST= 2999 and ALT= 4370. All the symptoms were remitted by the 3rd week of disease. The ELISA testing for anti-Hepatitis E virus IgM, was positive. In both cases other viral hepatitis serologic tests were negative. We make a description of these 2 cases and a literature review, because these both, are the first cases of Hepatitis E described in our city, and for the relevance of this virus in current medical knowledge for patients with non A, non B, non C acute hepatitis.

Epstein-Barr Virus Hepatitis Masquerading as Painless Jaundice.

Epstein-Barr virus (EBV) infection typically presents with pharyngeal symptoms and subclinical transaminitis. We present a case of a 27-year-old woman with no known past medical history who presented with painless jaundice and dark-colored urine for three days. Her review of systems was negative for fever, sore throat, nausea, vomiting, pruritus, or rash. Her last sexual contact was six months ago with a male partner, and she only drank alcohol socially. Family and surgical history were non-significant. Physical examination revealed 3+ bilateral conjunctival icterus without abdominal tenderness or organomegaly. She had elevated transaminases: alanine transaminase (ALT) of 1287U/L and aspartate aminotransferase of (AST) 1057U/L but her alkaline phosphatase (ALP) was only slightly above normal at 109U/L (normal range 35-104U/L), with a direct hyperbilirubinemia - total bilirubin 9.5mg/dl, direct bilirubin 6.8mg/dl; the abdominal ultrasound revealed non-dilated bile ducts. Hepatitis A, B, and C serology was negative, but her EBV serology showed an infection. She had incidental thalassemia minor without splenomegaly or asterixis. She was managed conservatively, and her liver enzymes trended down with supportive management. Although EBV is an uncommon cause of painless jaundice, this diagnosis should be considered, especially when other more common causes of jaundice have been ruled out. A high index of suspicion should be maintained to detect EBV hepatitis as it can easily be diagnosed through serological testing.

Social history of viruses

Hepatitis is a disease of the liver that has been recognised since antiquity. Symptoms include jaundice, a yellowing of the skin, eyes and body fluids. There are numerous causes, including viruses – particularly hepatitis A virus, hepatitis B virus and hepatitis C virus. Throughout history epidemics of jaundice have been reported, mainly affecting soldiers at war. This "campaign jaundice" was common in the Middle Ages. It occurred among Napoleon's armies and during most of the major conflicts of the 19th and 20th centuries, including the American Civil War, where over 40,000 cases and around 150 deaths were reported. The viruses that cause epidemic jaundice were not discovered until the middle of the 20th century. The names for epidemic jaundice, hepatitis A, and for blood-borne infectious jaundice, hepatitis B, were first used in 1947, following a publication in 1946 giving evidence that the two diseases were distinct. In the 1960s, the first virus that could cause hepatitis was

Hepatitis -- History and Physical -- Viral Hepatitis

Phase 2 (prodromal phase) - Patients in this phase usually present with anorexia, nausea, vomiting, malaise, pruritus, urticaria, arthralgias, and fatigue. Many times these patients are misdiagnosed as having gastroenteritis or viral infection. Phase 3 (icteric phase) - Patients in this phase present with dark-colored urine and pale-colored stool. Some patients develop jaundice and right upper quadrant pain with liver enlargement. Phase 4 (convalescent phase) - Patients typically start noticing the resolution of symptoms, and laboratory studies show liver enzymes returning to normal levels. [32]

[Acute sporadic hepatitis caused by the E virus in Chile. Clinical case].

A 53 year old female nurse presenting with malaise, jaundice and pruritus is reported. Physical examination only disclosed jaundice and laboratory values showed an ALT of 445 U/l, ASAT of 179 U/l, alkaline phosphatases of 455 U/l and a total bilirubin of 7.7 mg/dl. Serological markers for hepatitis virus E were positive and negative for hepatitis virus A, B and C, cytomegalovirus and Epstein Barr virus. The patient recovered fully in 10 weeks and is asymptomatic after 5 years of follow up. Health care workers probably have a higher risk for hepatitis E than the general population and this is the first acute sporadic case described in Chile.

First_Aid_Step2

Exam often reveals jaundice, scleral icterus, tender hepatomegaly, possible splenomegaly, and lymphadenopathy. Chronic hepatitis usually gives rise to symptoms indicative of chronic liver disease (jaundice, fatigue, hepatosplenomegaly). At least 80% of those infected with HCV and 10% of those with HBV will develop chronic hepatitis. Dramatically ↑ ALT and AST and ↑ bilirubin/alkaline phosphatase are present in the acute form. In chronic hepatitis, ALT and AST are ↑ for > 6 months with a concurrent ↑ in alkaline phosphatase/bilirubin and hypoalbuminemia. In severe cases, PT will be prolonged, as all clotting factors except factor VIII are produced by the liver. The diagnosis of viral hepatitis is made by hepatitis serology (see Table 2.6-8 and Figure 2.6-11 for a description and timing of serologic markers) and by liver biopsy in chronic or severe cases.

Jaundice -- History and Physical -- History

Patients usually present with varying symptoms apart from yellowish discoloration of skin along with pruritus, thus providing clues to narrow down the etiology or can also be asymptomatic. A thorough questioning regarding the use of drugs, alcohol or other toxic substances, risk factors for hepatitis (travel, unsafe sexual practices), HIV status, personal or family history of any inherited disorders or hemolytic disorders is vital. Other important points include the duration of jaundice; and the presence of any coexisting signs and symptoms, like a joint ache, rash, myalgia, changes in urine and stool. [22] A history of arthralgias and myalgias before yellowing indicates hepatitis, either due to drugs or viral infections.

[Results of the biochemical examination of persons who were in contact with infectious hepatitis patients].

The results or biochemical examination (by the micromethod) of persons having close contacts with infectious hepatitis patients and persons living outside the foci of this infection in one of the regions of the Uzbek SSR with unfavorable situation in respect of infectious hepatitis are presented. Among the first group of persons those with hyperenzymemia constituted 2%. Outside the foci of infection such persons constituted 1.5%. The ratio of the frequency of the laboratory diagnosis of the disease to the number of officially registered cases was 0.1:1.0. The greatest percentage of persons with biochemical shifts was established in October-December (2.2-3.4) and among the patients examined after the 20th day of hospitalization (2.6 ), as well as among children under 7 years (3.2) and in the age group 20-29 years (2.6).

Fatal hepatitis E viral infection in pregnant women in Ghana: a case series.

Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy.Case 1 was a 31-year-old Ghanaian woman who presented with a week's history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died.Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation.Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana.

[Natural history of viral hepatitis A in Chilean adults: clinical and laboratory aspects].

In many countries, Hepatitis is mainly due to virus. A. When improving life condition in a given population, initially there is a tendency to increase the number of cases in adults. We report clinical and laboratory findings in 87 adults with acute viral Hepatitis A in Chile. The rate man/woman was 1.55/1. Mean age: 23.8 years. Clinical forms: icteric classical (77.01%), cholestatic (10.34%), anicteric (8.05%), biphasic (2.30%) and fulminant (2.30%). From 87 patients in consult 1, 64 were controlled at day 15 (consult 2) and 35 one year later (consult 3). Laboratory (means): ALT (UI/L): 856.8, 111.6 and 20.8 in consult 1, 2 and 3 respectively. Correlation between values of ALT and AST (p < 0.0001). Mean total bilirubin (mg%): 6.6, 2.5 and 0.8 respectively. The evolution of Hepatitis A was favorable with a rapid decrease of clinical signs and normalization of laboratory values within the 3 first weeks of disease.

InternalMed_Harrison

Benign Recurrent Intrahepatic Cholestasis (BRIC) This rare disorder is characterized by recurrent attacks of pruritus and jaundice. The typical episode begins with mild malaise and elevations in serum aminotransferase levels, followed rapidly by rises in alkaline phosphatase and conjugated bilirubin and onset of jaundice and itching. The first one or two episodes may be misdiagnosed as acute viral hepatitis. The cholestatic episodes, which may begin in childhood or adulthood, can vary in duration from several weeks to months, followed by a complete clinical and biochemical resolution. Intervals between attacks may vary from several months to years. Between episodes, physical examination is normal, as are serum levels of bile acids, bilirubin, transaminases, and alkaline phosphatase. The disorder is familial and has an autosomal recessive pattern of inheritance. BRIC is considered a benign disorder in that it does not lead to cirrhosis or end-stage liver disease. However, the episodes

Cases from the Osler Medical Service at Johns Hopkins University.

A 37-year-old woman presented with increasing abdominal pain and jaundice. Six weeks before admission, she developed persistent diarrhea and jaundice of the skin. She also bruised easily, and her gums bled. In the subsequent weeks, her appetite decreased, she was fatigued, and she had nausea, vomiting, and abdominal distension. She had a history of drinking 1 quart of vodka every day for 20 years, with brief periods of abstinence; she stopped consuming alcohol 11 days before admission because it no longer provided symptomatic relief. Her past medical history was also notable for depression, including a suicide attempt 4 years earlier. She did not smoke, use illicit drugs, or have unprotected sexual intercourse. She had received no blood transfusions and had not traveled recently. She took no medications, except for occasional ibuprofen. On physical examination, she was thin and deeply jaundiced, and she trembled and responded slowly to questions. She was afebrile but tachypneic, and she had orthostatic hypotension. Her HEENT examination was notable for scleral and sublingual icterus, as well as crusted blood on her gums and teeth. The jugular veins were flat. The cardiac examination revealed tachycardia (heart rate, 103 beats per minute) without murmurs, rubs, or gallops. The abdomen was nontender and protuberant, with hypoactive bowel sounds; the spleen was not palpable, and there was no fluid wave or caput medusae. The liver percussed to 18 cm, with a smooth edge extending 10 cm below the costal margin. She had cutaneous telangiectases on her chest and bilateral palmar erythema. There was no peripheral edema. The neurologic examination was notable for asterixis. Her stool was guaiac positive. Laboratory studies revealed the following values: hematocrit, 21.2%; white blood cells, 17,310/mm(3); ammonia, 42 micromol/L; serum creatinine, 3.9 mg/dL; serum urea nitrogen, 70 mg/dL; albumin, 2.1 g/dL; total bilirubin, 26.8 mg/dL; alanine aminotransferase, 14 U/L; aspartate aminotransferase, 77 U/L; alkaline phosphatase, 138 U/L; prothrombin time, 103 seconds (international normalized ratio, 10.6); and urinary sodium, <5 mg/dL. Urinalysis revealed an elevated specific gravity and numerous muddy granular casts. Hepatitis A, B, and C serologies were negative. On abdominal ultrasound examination, there was no ascites, and the liver was echogenic. The portal and hepatic veins were patent, and the hepatic arteries were normal. The spleen measured 14 cm. What is the diagnosis?

Social history of viruses

jaundice, hepatitis B, were first used in 1947, following a publication in 1946 giving evidence that the two diseases were distinct. In the 1960s, the first virus that could cause hepatitis was discovered. This was hepatitis B virus, which was named after the disease it causes. Hepatitis A virus was discovered in 1974.

Ginseng-Related Drug-Induced Liver Injury.

Ginseng is commonly used as a medicinal herb for memory and concentration and general well-being. Drug-induced liver injury (DILI) is one of the most challenging disorders and trending events in the United States which are related to body building and weight loss supplements. Currently, herbal and dietary supplementation is the second most common cause of DILI. Here, we report on a 45-year-old healthy Chinese woman who presented with dull intermittent left upper quadrant abdomen pain for a month. Upon thorough history taking, she had been taking ginseng tea and supplementation for her menopausal symptoms for almost 3 months. Physical examination was unremarkable except mild tenderness in left upper quadrant of the abdomen. Liver function test showed aspartate transaminase (AST) 717 U/L, alanine transaminase (ALT) 343 U/L, total bilirubin 5 mg/dL, direct bilirubin 3.3 mg/dL, alkaline phosphatase 182 U/L, with international normalized ratio (INR) 1.2. Prior liver enzymes (6 months earlier) showed AST 21 U/L, ALT 18 U/L, total bilirubin 0.8 mg/dL, direct bilirubin 0.3 mg/dL, alkaline phosphatase 34 U/L, with INR 0.7. Viral serology for acute hepatitis B, C, E, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus was negative. She was immune to hepatitis A. Her antinuclear antibody was positive. Her anti-Smith antibody, anti-smooth muscle antibody, HFE gene mutation, ceruloplasmin, alpha-1 antitrypsin serologies were within normal references. An abdomen sonogram showed fatty infiltration. Liver biopsy showed moderate to severe portal inflammation and marked lobular disarray. Portal and lobular inflammatory infiltrates consisted of a mixture of histiocytes, lymphocytes, plasma cells, eosinophils, and neutrophils with centrilobular necrosis and focal bridging necrosis, and necro-inflammation. After 6 weeks of follow-up, the patient improved physically, and the abdomen pain resolved. Ginseng has been widely used in the Chinese community as medicinal herb for a variety of conditions for decades. However, proper research has never been done regarding its pharmacokinetics, efficacy, and safety issues. In our case report, the idiosyncratic DILI resulted from ingestion of ginseng as herbal supplementation for premenopausal symptoms. Physicians should be aware of and suspect DILI in any patient with acute liver injury, and patients should be reminded that all medications and supplements have a potential to cause DILI.

Spontaneous Cure of Acute Hepatitis C.

The statistics proved that approximately 25% of the patients with acute HCV present with jaundice, and only 10-20% develop gastrointestinal symptoms. We present the case of a 58 year-old woman, with prior antecedents of arterial hypertension and diabetes mellitus since 25 years old, hypercholesterolemia and hypertriglyceridemia, psoriasis, epilepsy and depressive syndrome. She clinically presents asthenia, anorexia, itching, jaundice and choluria. The objective examination showed an orientated patient, without flapping, hemorrhagic dyscrasia or signs of chronic hepatic disease, with icteric mucosa and skin, abdominal pain, with hepatomegaly and splenomegaly. The laboratory tests have been compatible with acute hepatitis with colestatic pattern: AST/ALT 969/798 UI/ml, FA 796 UI/ml, GGT 2476 UI/ml, BT/BD 7.39/6.10, INR 0.9. The abdominal echography showed: hepatomegaly, regular borders, hepatic steatosis, splenomegaly without ascitic fluid. The viral serological tests revealed protection for hepatitis A ( IgM neg/IgG pos), negative for HVB infection (AgHBs neg, anti-HBc neg), negative for HVE and other viruses (CMV Herpes virus, Epstein Barr, HIV), positive antibodies for HCV and positive RNA VHC (164200 UI/ml), HCV genotype 3a, IL-28B CT, negative autoimmunity. The previous HCV tests were negative, sustaining the recent infection. We assumed an acute hepatitis C. The patient was symptomatically treated with hydroxyzine for the skin itch, with vitamin K for INR correction and she was closely monitored. She had good clinical and laboratorial evolution and she was discharged after one week, maintaining hepatology consultation. She spontaneously cleared HCV infection after 3 months, maintaining negative RNA VHC 6 months after infection. The patient has cured the HCV infection with no need for antiviral treatment.

[Viral hepatitis C. Personal experience with diagnostic, monitoring and epidemiologic studies].

In the period from 1991 to 1993, 18 patients with the acute viral hepatitis type C were treated and followed up--13 men and 5 women, the average age of 42 years. The group of 6 patients (4 men and two women) with the "old" proven liver cirrhosis, whose etiology was unknown for 20 years, was analyzed. The investigations showed that the acute viral hepatitis type C usually began with the mild subjective disorders. The half of the patients did not have either jaundice or hepatomegaly, only half of them recover, and the first cases of cirrhosis could have been expected almost as early as a year after the beginning of illness. The developed liver cirrhoses remained compensated for years. About 58% of patients got infected parenterally, and the rest of them could have gotten infected in other manner. ELISA test showed great reliability in proving the antibodies against the viral hepatitis type C in the confirming the diagnosis of illness.

Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A.

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.

[Hepatitis A in Iceland].

Hepatitis A virus (HAV) epidemics occurred repeatedly in Iceland in the early 20th century, but since then few cases have been reported and no epidemics since 1952. The latest Icelandic studies on HAV from around 1990 showed low incidence of infection and de-- creasing prevalence of antibodies. The objective of this study was to determine the incidence, clinical presentation and origin of HAV, abroad or in Iceland. A retrospective search was undertaken on all patients with positive anti-HAV IgM during the 11 years period of 2006-2016 in the virological database of the National University Hospital of Iceland. Clinical data was collected from medical records on symptoms at diagnosis, blood test results and possible route of transmission. A total of 12 individuals were diagnosed with acute hepatitis A during the period and 6691 HAV total andibody tests and 1984 HAV IgM antibody tests were performed. Nine (75%) had been abroad within 7 weeks from initial symptoms. The most common symptoms were jaundice (83%), fever (67%) and nausea and/or vomiting (58%). 50% were admitted to a hospital. 42% had elevated INR/PT. Everyone sur-vived without complications. Annually, approximately one case of acute hepatitis A was diagnosed in Iceland during the study period but a very high number of antibody tests were performed. The majority of cases occurred among individuals who had recently been abroad. If patients have jaundice, fever and nausea, testing for HAV infection should be undertaken. HAV is not endemic in Iceland.

Hepatitis -- History and Physical -- Hepatitis G

Patients with hepatitis G infection can have a mild infection without jaundice, but most patients are asymptomatic. There have been few reports of fulminant and chronic hepatitis as well as hepatic fibrosis also, but it is not common. The patient can have an elevation of alkaline phosphatase and gamma-glutamyl transpeptidase as well, but most patients infected with the hepatitis G virus have normal liver function tests [24] .

Polyarteritis nodosa

A patient is said to have polyarteritis nodosa if he or she has three of the 10 signs known as the 1990 American College of Rheumatology (ACR) criteria, when a radiographic or pathological diagnosis of vasculitis is made: Weight loss greater than/equal to 4.5 kg Livedo reticularis (a mottled purplish skin discoloration over the extremities or torso) Testicular pain or tenderness (occasionally, a site biopsied for diagnosis) Muscle pain, weakness, or leg tenderness Nerve disease (either single or multiple) Diastolic blood pressure greater than 90 mmHg (high blood pressure) Elevated kidney blood tests (BUN greater than 40 mg/dL or creatinine greater than 1.5 mg/dL) Hepatitis B (not C) virus tests positive (for surface antigen or antibody) Arteriogram (angiogram) showing the arteries that are dilated (aneurysms) or constricted by the blood vessel inflammation

[Epidemiologico-clinical considerations on a case file of acute hepatitis observed 1980-1983].

Between January 1980 and December 1983, 332 consecutive cases of acute hepatitis were observed in adult patients admitted to the Department of Infectious Disease and Gastroenterology of Siena. Sex and age of the patients, the presence of jaundice, the maximum value of the serum-glutamate-pyruvate-transaminase (SGPT) were considered. Serum specimens were tested for hepatitis B surface antigen (HBsAg), antibody against hepatitis B core antigen (anti-HBc) of the IgM class, antibody against hepatitis A virus (anti-HAV) of the IgM class, antibody against cytomegalovirus (CMV) of the IgM class, Paul Bunnel Davidshon reaction. Hepatitis A was diagnosed in 25 cases (7.5%). Hepatitis B in 167 (50.3%). Hepatitis due to CMV in 2 cases (0.6%). And, by exclusion, hepatitis non A, non B in 138 cases (41.6%). Male patients were affected with significantly higher frequency than female (p less than 0.01); the same was seen for young patients (14-30 years) compared to the older ones (31-50 years, and over 50 years) (p less than 0.01 in both). Biochemical investigation showed that hepatitis A and B had a significantly higher, maximum SGPT value than hepatitis non A non B (p less than 0.01 in both). Icteric patients were significantly more frequently observed among hepatitis A and B cases than hepatitis non A non B cases (p less than 0.01 in both).

Intrahepatic cholestasis occurring with prurigo of pregnancy.

A 23-year-old woman presented to our polyclinic complaining of itching, generalized dermatitis, and jaundice. She was in her 31st gestational week and had developed pruritus and the dermatitis since the first month of pregnancy; her jaundice started about a month before presentation. Her history included similar complaints in a previous pregnancy, which resulted in premature birth of a baby with a permanent brain defect. One of her sisters had had jaundice and itching in her 27th gestational week and delivered a healthy baby; a second sister had experienced itching and dermatitis in her second trimester and delivered a healthy baby. Physical examination of the patient showed that her eyes were jaundiced (Figure 1); skin examination revealed generalized erythematous excoriated papules, symmetrically distributed all over her body (Figure 2 Figure 3). Laboratory analyses revealed the following results: leukocyte count, 14.30/mm(3) (3.8-10.3/mm(3)); erythrocyte sedimentation rate, 25 mm/h (<20 mm/h); aspartate aminotransferase, 44 U/L (5-40 U/L); alanine aminotransferase, 63 U/L (5-40 U/L); lactate dehydrogenase, 1158 U/L (220-450 U/L); total bilirubin, 6.88 mg/dL (<1.10 mg/dL); and direct bilirubin, 3.27 mg/dL (<0.35 mg/dL). Urinalysis results were positive for bilirubin and urobilinogen. Positive serologic findings included rubella immunoglobulin G, 93 AU/mL (<15) and cytomegalovirus, 188 AU/mL (<10); negative findings included herpes simplex virus type 2 and hepatitis. Histopathologic examination of material collected from the left breast via punch biopsy showed parakeratosis, acanthosis, and perivascular lymphocyte infiltration in dermal vessels. Treatment with 2 g/d cholestyramine and a topical corticosteroid was effective in the patient, who was diagnosed with intrahepatic cholestasis of pregnancy and prurigo of pregnancy based on the clinical, histopathologic, and laboratory findings. To the authors' knowledge, this is the first such reported case in the literature.

Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications.

A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had taken a five-day course of amoxicillin-clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 × 10<sup9</sup/L (normal 3.6-9.3), haemoglobin 11.8 g/dl (normal 11-15), platelet count 356 × 10<sup9</sup/L (normal 170-420), sodium 138 mmol/L (normal 134-144), potassium 3.5 mmol/L (normal 3.5-5.0), creatinine 32 µmol/L (normal 40-75), albumin 30 g/L (normal 35-48), alanine aminotransferase 707 IU/L (normal 15-54), alkaline phosphatase 151 IU/L (normal 30-130), bilirubin 384 µmol/L (normal 7-31) and prothrombin time 27.2 s (normal 11.7-14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells. Her clinical condition deteriorated in the following days with prothrombin time and bilirubin rising to 56.6 s and 470 µmol/L, respectively. At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. Human leucocyte antigen (HLA) typing was performed as a part of preparatory investigations and showed the patient carried the HLA haplotype HLA-DRB1∗15:02-DQB1∗06:01. Following orthotopic transplantation of a deceased donor graft her explant histology revealed severe ongoing hepatitis with multi-acinar necrosis (Fig. 1A and B). This case raised a number of important questions about the diagnosis of drug-induced liver injury and tools available for clinicians to make the best decisions for patient care: In this Grand Rounds article, we will explore these questions, describing the pathophysiology, diagnostic and prognostic biomarkers, and clinical management of drug-induced liver injury. We will also discuss ongoing areas of uncertainty.

[Recurrences of viral hepatitis A].

The aim of the study was to examine the frequency, severity, persistence and etiology of relapses occurring during the hepatitis A viral infection. Therefore, a prospective study of 910 patients suffering from hepatitis A (HA) was carried out. The clinical examination and determination of glutamyl pyruvic transaminase (GPT) in the serum every 7-14 days till recovery (usually during 6--8 months) were performed. HAV infection was confirmed by detecting anti-HAV IgM in the blood of all the examined by radioimmunoassay. In 876 (93.3%) patients HA had typical clinical features and a monophasic course. All cases made a rapid clinical recovery and liver function tests improved strikingly between 1 and 4 months after the onset of illness. However, in 34 (3.7%) of 910 patients, after an asymptomatic interval of 4--8 weeks, relapsing hepatitis occurred. Mild clinical symptoms: fatigue, myalgia, nausea, epigastric discomfort accompanied by the elevated levels of GPT in the serum were noticed in 11 patients, while 3 of them redeveloped jaundice. In 23 remaining patients relapses of hepatitis were asymptomatic, except for the reappearance of icterus in six cases. The only way to establish the exacerbation of the disease was through the pathological findings of GPT in the serum, which increased 10--60 times above the upper limit of the normal value. While 25 patients had one relapse, in 9 there were two or more relapses, so that hepatitis had a biphasic or polyphasic course. The second relapse was registered 3--6 weeks after the first one disappeared. Through biochemical tests the average values of the GPT were established: 1566 U/L in the acute stage, 107 U/L during the early stage of convalescence and 1016 U/L during the first relapse of hepatitis. After the first relapse and during remission, in 9 patients the average values of GPT in the serum were 84 U/L, while during the second relapse 518 U/L. Clinical signs of relapsing hepatitis disappeared approximately in 4 days, but liver function tests decreased slowly and persisted elevated between 5 and 12 months. A possibility of establishing the etiology of relapsing hepatitis, which has yet remained unknown, is discussed. Anti-HAV IgM were present in all 34 patients during the initial and relapsing phase of hepatitis and in 26 cases in the latter phase of convalescence between 9 and 11 months after the beginning of the disease. Serological tests excluded infection with hepatitis B, cytomegalovirus and Epstein-Barr virus. With a great probability other infections and toxic agents damaging the liver could have been excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Cholestatic Liver Injury From Hydralazine Intake.

Hydralazine is a commonly used oral antihypertensive agent. We report a rare case of hydralazine-induced hepatotoxicity in the form of subacute hepatic necrosis. A 75-year-old African American woman presented with jaundice of 7-day duration. She was started on hydralazine 100 mg 3 times a day 10 weeks before presentation. On physical examination, scleral icterus was noted. Workup revealed elevated liver transaminases, alkaline phosphatase, and conjugated bilirubin. She had no history of liver disease, and liver function tests had been normal before starting hydralazine. Other etiologies, including viruses, common toxins, drugs, autoimmune, and copper-induced hepatitis, were excluded. Abdominal imaging studies did not show any evidence of intrahepatic or extrahepatic biliary ductal dilatation, and no pathologies were seen in the liver and pancreas. The patient's liver biopsy revealed extensive lobular hepatitis, significant necrosis, mixed inflammatory infiltrate, and no significant fibrosis, supporting a diagnosis of drug-induced liver injury. Hydralazine was immediately discontinued. She showed improvement of clinical and laboratory abnormalities within 5 days after discontinuation of hydralazine. To establish the diagnosis of hydralazine-induced liver injury, we used assessment tool outlined by the Council for International Organization of Medical Sciences (CIOMS) scale that led to "high probable" relationship. Although rare, clinically significant, and potentially life-threatening liver injury can result from use of hydralazine. Both clinical and histological presentations in our patient suggest acute liver injury. The hydralazine-induced hepatitis seems to be reversible as discontinuation of the drug improves clinical outcomes. We highly recommend monitoring of the liver function during hydralazine treatment.

[The characteristics of the course of viral hepatitis C].

Time-related course and results of examination were studied in patients with viral hepatitis C, having gotten infected through blood. Based on the comparison of similar indicators in patients with viral hepatitis B particular features were revealed of the clinical course of viral hepatitis C. These are as follows: short-in-duration prejaundice period, in other instances there is no prejaundice period at all, subfebrile states set in quite often; among other features are dyspepsia-like events together with signs of a damage to pancreas. There has been noted a slow dynamics of the icteric period reversibility, with biochemical indicators showing the same tendency.

[Manganese superoxide dismutase-inhibiting autoantibodies in cholestatic Epstein-Barr viral hepatitis].

A 21-year-old woman reported no serious previous illness. For 3 days before admission she had a fever, headache and joint pains. She had become progressively more jaundiced. Physical examination was normal except for enlarged liver and spleen, swollen lymph nodes and facial oedema. GOT (30 U/l), GPT (33 U/l) and alkaline phosphatase (172 U/l) were slightly elevated. Serum bilirubin was raised to 12.4 mg/dl. The total white blood cell count was normal, but there were 45% atypical lymphocytes (activated T lymphocytes). Abdominal sonography and endoscopic retrograde cholangiopancreatography were unremarkable. Serology for hepatitis A, B and C as well as for antimitochondrial antibodies was negative, but there were specific IgM (1:640) and IgG antibodies (1:80) against Epstein-Barr virus (EBV) capsid antigen in the immunofluorescence test. The EBV infection (infectious mononucleosis) was complicated by cholestatic hepatitis. High concentrations (1832 Göttingen units/ml) of enzyme-inhibiting autoantibodies against the antioxidative enzyme manganese-superoxide dismutase (MSD) were demonstrated. The autoantibodies reduced the antioxidative action of the enzyme by more than 70% and favoured the oxidative cell damage in vitro. After bed-rest for one week without further treatment the symptoms improved and the abnormal laboratory values, including the autoantibodies against MSD, regressed. Autoantibodies against MSD are formed during an acute infection with EBV. Their enzyme-inhibiting action promotes abnormalities of oxidative cell function and may thus be the cause of cholestatic hepatitis in this infection.

Augusto Murri

Murri is particularly concentrated on the observation and analysis of the events in order to reach the right diagnosis and also an appropriate therapy. His works "Sulla natura del processo morboso dell’itterizia grave" ("The nature of the morbose process of the severe jaundice") "Nosologia e psicologia" ("Nosology and psychology") "Lezioni di clinica medica" ("Lectures on medical clinic") References Bibliography

Cerebral Venous Sinus Thrombosis in Systemic Lupus Erythematosus.

A 38-year-old woman presented with general weakness and vaginal bleeding. One month prior, she had been diagnosed with Evans syndrome (haemolytic anemia with positive Coombs test and thrombocytopenia) and was given oral steroid as maintenance therapy. Her serology examination was negative for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Her obstetrical history was marked by miscarriage in second pregnancy and preeclampsia in third pregnancy. She used hormonal contraceptives until 5 months prior to admission. On physical examination, she had anemic conjunctiva and no organomegaly. Blood tests were significant for anemia (3.4 g/dl) and thrombocytopenia (28,000/µl). Her vaginal bleeding had ceased, however her platelet continued decreasing to 12,000/µl during first several days of hospitalization despite receiving platelet transfusion. On the tenth hospital day, she suddenly complained of severe headache and blurred vision. She had bilateral edema and erythema of palpebral, chemosis, decreased in visual acuity, and reduced ocular motility. Ear and nose examination were normal. Peripheral blood smear showed no blast. Prothrombine time (PT), INR, APTT tests were normal and D Dimer was slightly increased (3.3 mg/l; NV ≤0.5 mg/l). Urine examination revealed proteinuria with 24 hour urine protein was 1,863 mg (NV <150 mg/day). We assessed her as cavernous sinus thrombosis and treated her empirically with intravenous broad-spectrum antibiotics, morphine drip. Either digital subtraction angiography or anticoagulant was deferred due to low platelet. Further examination revealed positive for ANA, anti-SSA, and diagnosis of SLE was established. Anticardiolipin antibodies of IgG and IgM and anti-beta2 glycoprotein antibodies of IgM and IgG tests were non reactive. Methylprednisolone pulse therapy (1g/day) was given for 3 consecutive days, and then tapered to oral methylprednisolone. She additionally received azathioprine 50 mg tab BID. Meanwhile her clinical symptoms alleviated and platelet count was increased, brain MRI and MR venography finally performed suggesting cerebral venous sinus thrombosis. She got additional oral anticoagulant rivaroxaban 15 mg tab BID and eventually discharged. Cerebral venous sinus thrombosis may be the presenting symptoms or occur concomitantly within the onset of SLE. Our patient had SLE, meeting 4 of the Systemic Lupus International Collaborating Clinic classification criteria (hemolytic anemia, thrombocytopenia, renal involvement, and positive for ANA test). Vasculitis due to endothelial cell injury mediated by immune-complex deposition is proposed to be the pathogenesis of CVST in SLE. Hypercoagulable state could be other etiology factor. Antiphospholipid antibodies were absent in our case as reported in some cases, emphasizing vasculitis as the underlying mechanism. Treatment of CVST in SLE consisting of anticoagulant, steroid, and immunosuppressant. This case elicits intriguing problem: CVST and thrombocytopenia. Anticoagulant treatment is proposed as the cornerstone treatment for CVST, however it was deferred due to risk of bleeding in thrombocytopenia. Steroid plays role in treatment of CVST in SLE, owing to its anti-inflammatory property. As shown in previous cases, the patient had remarkable response to high dose steroid treatment and eventually got anticoagulant after her platelet had increased. In summary, prompt diagnosis and treatment of CVST are important for a favorable prognosis.

PBC-AIH overlap syndrome with concomitant ITP and Hashimoto's disease with positivity for anti-centromere antibody.

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimoto's disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6 g/dl; gamma-globulin (glb), 35.9%; total bilirubin (T-bil), 9.41 mg/dl; direct bilirubin (D-bil), 7.52 mg/dl; aspartate aminotransferase (AST), 957 U/l; alanine aminotransferase (ALT), 651 U/l; alkaline phosphatase (ALP), 595 U/l; gamma-guanosine triphosphate (GTP), 129 U/l; IgG, 2620 mg/dl; IgM, 223 mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimoto's disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study.

<bCASE STUDY</b RS, a 36-year-old female, presented to the emergency department (ED) of a large academic medical center upon the advice of her primary care provider because of 3 weeks of progressive mental status changes, weakness, and decreased oral intake. According to her husband, RS was diagnosed with stage IIIA large cell lung cancer 8 months earlier and was treated with concurrent chemotherapy (carboplatin, pemetrexed, and bevacizumab) and radiation therapy that was completed 4 months prior to admission. No other specific information about her treatment or outside health records was available. According to her husband, RS had been in her usual state of health until approximately 3 weeks prior, when she began having significant mental status changes. She first exhibited some difficulty finding words and later was noted to be putting food in a coffee maker. This spontaneously resolved after approximately 1 week; however, she rapidly developed slurred speech and began to make nonsensical statements. These manifestations also slowly improved but were followed by worsening speech deficit, difficulty walking, and impaired balance. During one of these episodes, she had an occurrence of incontinence. Her husband also noted an incident where her "eyes were beating back and forth and the left side of her face was twitching." RS also had periods (according to her husband) where she "did not seem to be interacting with her environment." These progressively worsened during the last week, and she completely stopped walking and talking 2 days prior to coming to the ED. According to her husband, RS had rheumatoid arthritis and no surgical history. Her family history was unknown except that RS's mother had "seizures." RS had reportedly not used tobacco, alcohol, or drugs, and she was sexually active with her husband. Home medications included transdermal fentanyl 12 μg/hr patch changed every 72 hours; oxycodone-acetaminophen tablets 5-325 mg, two every 4 hours as needed for pain; prednisone 10 mg, one tablet daily; and megestrol 40 mg/mL suspension, 20 mL once daily for appetite stimulation. RS was admitted to an inpatient medical oncology service and evaluated by the oncology advanced practitioner (AP) on her second inpatient day. Upon exam, RS was nonverbal except for moaning in response to painful stimuli and to her sister's voice. Her vital signs were normal. She appeared ill but well-nourished, and she was mildly diaphoretic. Neurologic examination revealed that her pupils were slightly sluggish but equal, round, and reactive to light. Extraocular muscle movements were intact, but she did not move her eyes in response to commands. She tracked the AP and family members around the room with her eyes. Cranial nerve examination was intact with the exception of cranial nerves IX, X, and XI, which were difficult to examine given her inability to cooperate and open her mouth. Motor examination revealed increased tone throughout and intermittent, inconsistent resistance to passive movement. She was seen to move all four extremities spontaneously although not in response to commands. Deep tendon reflexes were intact and equal in all extremities. Examination of other body systems was as follows: there was dry, peeling skin on her lips, but her mucous membranes were moist and free of erythema or lesions. Her lungs were clear to auscultation bilaterally. Her heart rate and rhythm were regular, there were no murmurs, rubs, or gallops, and distal pulses were intact. Her abdomen was nondistended with normally active bowel sounds in all four quadrants. Her abdomen was soft, nontender to palpation, and without palpable masses. There was no peripheral discoloration, temperature changes, or edema, and examination of her skin was benign. <bWorkup</b On admission to the emergency department, serum laboratory studies were unrevealing for any potential causes of encephalopathy. Kidney and liver function were normal, making diagnoses of uremic and hepatic encephalopathies less likely. Cultures of the urine and blood were negative. Samples of cerebrospinal fluid (CSF) were obtained via lumbar puncture and were unrevealing for any abnormalities. Computed tomography (CT) of the head without contrast was negative for any acute intracranial process. Ultrasound of the right upper quadrant revealed a single, nonspecific, hypoechoic hepatic lesion. Computed tomography scans of the chest, abdomen, and pelvis demonstrated the primary malignancy in the upper lobe of the left lung, as well as possible metastatic disease within the left lung, right lung, and liver, and widespread osseous metastatic disease. Magnetic resonance imaging (MRI) of the brain performed 1 day after admission demonstrated numerous scattered punctate foci of enhancement throughout the supratentorial and infratentorial brain parenchyma, measuring at most 3 to 4 millimeters in diameter. There was no significant mass effect or midline shift. A paraneoplastic panel was sent to an outside laboratory and returned positive for antivoltage-gated potassium channel (VGKC) autoantibodies. <bDifferential Diagnosis</b Clinically, RS was exhibiting signs of encephalopathy, a broad term that indicates general brain dysfunction, the hallmark of which is altered mental status. Diagnosing encephalopathy is challenging, as many differential diagnoses must be considered. The clinician must consider metabolic derangements, toxic and infectious etiologies, psychiatric disorders, and less commonly, prion disorders and progressive dementia. Cultures of RS's blood and urine as well as other specialized endocrine tests were negative, decreasing the likelihood of a metabolic or infectious cause for her presentation. The abnormalities on her brain MRI were reviewed by a neuro-oncology team, who felt that the faint, nondescript nature of the visualized lesions was not suspicious for metastatic disease. Sequelae of seizures was also considered by neuro-oncology but dismissed given a grossly normal prolonged electroencephalogram. Some encephalopathies are caused by autoimmune or inflammatory mechanisms, which are confirmed by the presence of autoantibody markers and/or clear response to immunomodulatory treatment (Vernino, Geschwind, & Boeve, 2007). These types of encephalopathies have been seen in patients with cancer and have thus been termed paraneoplastic. The presence of anti-VGKC antibodies on RS's paraneoplastic panel directed the inpatient medical oncology team toward a paraneoplastic neurologic disorder (PND) as the most likely diagnosis.

[Primary biliary cirrhosis--analysis of clinical material].

The analysis is presented of 67 patients with primary biliary cirrhosis treated in the years 1971-1988. The group consisted of 60 women (89.5%) and seven men (10.5%). Presenting symptoms were mostly itching (66%) and jaundice (12%). The time between the onset of the first symptoms and the diagnosis was three years, on the average. Autoantibodies to mitochondria were present in 86% of patients. In 27% of cases markers of HB virus infection were found. Cholelithiasis was present in 19 patients (28%). Primary biliary cirrhosis was diagnosed with delay. Third degree of histological changes was observed in 38.8% of cases and in 18% of patients it was already fourth degree. Eighteen patients (27%) died after six years, on the average, from the onset of symptoms. The direct causes of death were, most frequently, liver failure and haemorrhage from oesophageal varices.