Cholestatic hepatitis induced by Epstein-Barr virus infection in an adult

Liver involvement is nearly universal in healthy persons with Epstein-Barr Virus (EBV) infection-induced infectious mononucleosis. It is usually mild, undetected clinically and resolves spontaneously. Jaundice is distinctly uncommon and may reflect either more severe hepatitis or an associated hemolytic anemia. Cholestatic hepatitis due to EBV infection is infrequently reported and may pose a diagnostic quandary. We describe a patient who presented with jaundice and a markedly elevated serum alkaline phosphatase level due to serologically confirmed acute infection with EBV. Imaging studies excluded biliary obstruction. Symptoms and laboratory abnormalities resolved spontaneously. EBV infection should be included in the differential diagnosis of cholestatic hepatitis in adults.     

Autoimmune hepatitis type-2 and Epstein-Barr virus infection in a toddler: art of facts or an artifact?

Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.     

Cholestatic jaundice during infancy: experience at a tertiary-care center in Bangladesh.

BACKGROUND AND OBJECTIVE: Cholestatic jaundice in early infancy is a difficult diagnostic problem. Early diagnosis is important for proper management. This retrospective study was conducted to find out the etiology and clinical profile of neonatal cholestatic disorders in Bangladesh. SETTING: Tertiary-care hospital in a developing country. METHODS: Clinical profile and cause of cholestatic illness were studied in 62 infants with cholestatic jaundice developing before three months of age and persisting for more than two weeks. RESULTS: Neonatal hepatitis (22; 35.5%--17 with TORCH, 5 with urinary infection), followed by biliary atresia (16; 25.8%) and idiopathic neonatal hepatitis (15; 24.2%), were the commonest causes of cholestasis. Mean age at presentation was 3.5 months. Ten (62.5%) of 16 biliary atresia cases were male and jaundice appeared before 14 days in 14 (87.5%) cases. CONCLUSIONS: Neonatal hepatitis, biliary atresia and idiopathic neonatal hepatitis were the common causes of neonatal cholestasis in infancy. Though cholestatic jaundice developed early, most of the cases presented late.     

Epstein-Barr Virus Infection Mimicking Drug-Induced Hepatitis in a Critically ill Patient During Antituberculosis Therapy

Introduction:

Although hepatitis is frequently observed during antituberculosis (anti-TB) therapy, acute viral hepatitis should be ruled out first, especially in the endemic areas. In addition to common types of viral hepatitis, ie, hepatitis A, hepatitis B, and hepatitis C viruses, Epstein-Barr virus (EBV) may result in hepatitis in some cases.

Case Presentation:

Herein, we reported a critically ill patient who developed cholestatic hepatitis in the intensive care unit during the anti-TB therapy, which was misdiagnosed as anti-TB agents-induced hepatitis in the beginning. Further serologic tests and liver biopsy confirmed the diagnosis of EBV hepatitis. In contrast to previously reported hepatitis by EBV, which had presented with transient liver dysfunction and self-limiting illness, hepatitis with progressive jaundice was followed by coagulopathy and encephalopathy in our case and the patient died of hepatic failure complications.

Conclusions:

According to the presented case and subsequent literature review on fatal EBV hepatitis, clinicians should consider EBV infection in the differential diagnosis when hepatitis occurs in critically ill patients during the anti-TB therapy. Although hepatitis caused by EBV is mostly self-limited, some might be fetal.     

A case of severe cholestatic jaundice with hyperthyroidism successfully treated with methimazole

Liver dysfunction is a common complication observed in patients with hyperthyroidism, however the dysfunction is always mild and obvious jaundice is rarely observed. We present the case of a 43-year-old man who suffered from hyperthyroidism complicated by severe jaundice. The jaundice likely occurred as a secondary consequence of cholestasis due to hyperthyroidism, since other causes such as drug-induced or autoimmune liver dysfunction were ruled out. Treatment with methimazole improved severe cholestatic jaundice in parallel with normalization of thyroid function. The mechanism of cholestasis as a secondary complication of hyperthyroidism has not been uncovered and there is no specific biochemical marker for cholestasis due to this hormonal disease at present. This case serves as a reminder that severe jaundice can be a manifestation of simple hyperthyroidism, and that administration of antithyroid drugs is an effective treatment for severe cholestatic jaundice in such cases.     

Plasmapheresis and corticosteroid treatment for persistent jaundice after successful drainage of common bile duct stones by endoscopic retrograde cholangiography

Prolonged cholestasis is a very rare complication of endoscopic retrograde cholangiography （ERC）. Only few cases with this complication are reported in the English literature. We report persisting cholestatic jaundice in a 73-year old man after successful therapeutic ERC for choledocholithiasis. Serologic tests for viral and autoimmune hepatitis were all negative. A second-look ERC was normal also. He denied any medication except for prophylaxis given intravenous 1 g ceftriaxon prior to the ERC procedure. After an unsuccessful trial with ursodeoxycholic acid and cholestyramine for 2 wk, this case was efficiently treated with corticosteroids and plasmapheresis. His cholestatic enzymes became normal and intense pruritis quickly resolved after this treatment which lasted during his followup period. We discussed the possible mechanisms and treatment alternatives of intrahepatic cholestasis associated with the ERC procedure.     

Cholestatic hepatitis as a rare side effect of therapy with ticlopidine

A 71-year-old man with chronic atrial fibrillation was treated with aspirin because of a right cerebral infarction. Oral anticoagulation was not initiated because of a secondary hemorrhagic transformation. Six years later after a left cerebral transient ischemic attack aspirin was replaced by ticlopidine. Two weeks after starting ticlopidine he experienced abdominal cramps and diarrhea. Also dark urine and gray-colored stools were noticed, so that the patient stopped taking ticlopidine. 40 days after starting ticlopidine he was admitted to our hospital because of cholestatic jaundice. Serum alkaline phosphatase (305 U/l) and gamma GT (143 U/l) were elevated, the total bilirubin was 18.6 mg/dl at peak. GOT and GPT were 2.7 fold increased. After exclusion of a viral infection and autoimmune disease liver biopsy was performed, which showed a centroacinar cholestasis compatible with a drug-induced liver damage. 79 days after discontinuation of the drug laboratory signs of cholestasis had disappeared. In patients in whom long-term therapy with ticlopidine is indicated regularly laboratory tests and clinical examinations should be done to recognize infrequent side effects such as the cholestatic hepatitis in time.     

Acute hepatitis E virus infection presenting as a prolonged cholestatic jaundice

Hepatitis E virus (HEV) is an enteric virus that usually causes a self-resolving hepatitis; although, it may be fatal, especially in pregnant women. Although HEV is endemic in Israel, there have been no recent local outbreaks. We report the case of a 70-year-old man who presented with painless jaundice. Ultrasound and abdominal computed tomography scan revealed gallstones, with no evidence of cholecystitis and no dilatation of the intra-or extrahepatic bile ducts. An open cholecystectomy was performed with intraoperative cholangiography. There was no evidence of choledocholithiasis. A subsequent endoscopic retrograde cholangiopancreatography was normal. His bilirubin level subsequently increased to a maximum of 25 mg/dL, and his gamma-glutamyl-transferase level reached 1,400 U/L. There was no evidence of any autoimmune or metabolic disease, and routine viral serology was normal except for immunoglobulin G to hepatitis A virus. A liver biopsy revealed an acute cholestatic picture. The jaundice resolved slowly after a period of 6 months. Hepatitis E virus RNA was isolated from the acute-phase serum and was not detectable in the convalescent serum. This case is a unique example of chronic cholestatic jaundice that we think is caused by acute HEV infection.     

The Overlap Syndromes of Autoimmune Hepatitis

Autoimmune hepatitis has two major variant phenotypes in which the features of classical disease are co-mingled with those of primary biliary cirrhosis or primary sclerosing cholangitis. These overlap syndromes lack codified diagnostic criteria, established pathogenic mechanisms, and confident management strategies. Their clinical importance relates mainly to the identification of patients who respond poorly to conventional corticosteroid treatment. Scoring systems that lack discriminative power have been used in their definition, and a clinical phenotype based on pre-defined laboratory and histological findings has not been promulgated. The frequency of overlap with primary biliary cirrhosis is 7–13 %, and the frequency of overlap with primary sclerosing cholangitis is 8–17 %. Patients with autoimmune hepatitis and features of cholestatic disease must be distinguished from patients with cholestatic disease and features of autoimmune hepatitis. Variants of the overlap syndromes include patients with small duct primary sclerosing cholangitis, antimitochondrial antibody-negative primary biliary cirrhosis, autoimmune sclerosing cholangitis, and immunoglobulin G4-associated disease. Conventional corticosteroid therapy alone or in conjunction with ursodeoxycholic acid (13–15 mg/kg daily) has been variably effective, and cyclosporine, mycophenolate mofetil, and budesonide have been beneficial in selected patients. The key cholestatic features that influence the prognosis of autoimmune hepatitis must be defined and incorporated into the definition of the syndrome rather than rely on designations that imply the co-mingling of different diseases with manifestations of variable clinical relevance. The overlap syndromes in autoimmune hepatitis are imprecise, heterogeneous, and unfounded, but they constitute a clinical reality that must be accepted, diagnosed, refined, treated, and studied.     

Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature.

OBJECTIVE: The aim of this study was to describe a case of acute acalculous cholecystitis occurring in the course of primary Epstein-Barr virus (EBV) infection. METHODS: The clinical features of the case were analyzed and compared to those of three other similar cases reported in the international literature. RESULTS: All cases occurred in European females with cholestatic hepatitis, presented with gallbladder wall thickening, and recovered uneventfully without the need for surgical intervention. CONCLUSIONS: Acute acalculous cholecystitis may occur during the course of acute EBV infection, especially in patients with cholestatic hepatitis. Clinicians should be aware of the possible involvement of the gallbladder during EBV infection to avoid unnecessary invasive procedures or the overuse of antibiotics.     

Variant syndromes in autoimmune hepatic diseases

Some autoimmune hepatic diseases patterns can be of difficult classification, sometimes as overlap of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and chronic viral hepatitis. The recognition of these forms is not so easy, but it is necessary for an effective therapeutic approach. At present, the specificity in these cases of the score system done and revised by the International Autoimmune Hepatitis Group is being discussed. Patients showing such diseases have different modalities of presentation of their hepatic disease and different courses. The role of histology appears to be important, but often the overlap of more manifestations is not helpful to a correct diagnostic definition. The variant syndromes could be classified as intermediate patterns of cholestatic forms and of autoimmune hepatic diseases or cholestatic forms of autoimmune hepatitis or hepatitic forms of cholestatic syndromes.     

Jaundice in Multiple Myeloma: The Role of Oxymetholone

Jaundice complicated the course of disease in 11 (41%) of 27 consecutive patients with multiple myeloma. In only one patient was myeloma cell infiltration of the liver the sole cause of jaundice. One patient was found to have carcinoma of the pancreas. In nine jaundice developed during therapy with the bone marrow stimulant oxymetholone. Liver histology in six of the nine showed cholestatic hepatitis or a predominantly cholestatic reaction; clinical events were consistent with oxymetholone-induced cholestasis in the remaining three. In addition to oxymetholone all patients were receiving intermittent therapy with melphalan, prednisolone and procarbazine, but such therapy was not temporally related to the onset of jaundice. All jaundiced patients were HB_sAg negative. Of the 19 patients treated with oxymetholone for refractory anaemia, nine (47%) developed jaundice. The reason for such a high complication rate is obscure. Three of these patients, who showed a severe cholestatic hepatitis, died in acute liver failure. These results indicate that high doses of oxymetholone should be used with great care in the therapy of refractory anaemia in multiple myeloma.     

Differenzialdiagnose Ikterus

Jaundice is the result of increased serum bilirubin levels. An initial differentiation of the underlying causes can be made by distinguishing increased conjugated and non-conjugated serum bilirubin and the findings of abdominal ultrasound examination. This combined approach enables a first classification into extrahepatic causes, hepatocellular dysfunction and intrahepatic and extrahepatic forms of cholestasis. In each diagnostic category of jaundice the differential diagnosis can be improved by additional imaging techniques comprising helical CT scanning, MRCP or ERCP, targeted laboratory tests and finally a liver biopsy. Specific difficult-to-diagnose cholestatic diseases include primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis PBC and PSC overlap syndromes, IgG4 cholangiopathy and familial deficiency of biliary transporters due to mutations in the ATP8B1, ABCB11, ABCB4 and Jag1 genes. Molecular genetic testing enables these familial conditions to be differentiated.     

Epstein-Barr virus induced hepatitis: An important cause of cholestasis.

INTRODUCTION:: Epstein-Barr virus (EBV) infection frequently involves the liver, presenting as elevations in transaminases. EBV infection associated hepatitis, presenting with hyperbilirubinemia is rare. We describe a case of infectious mononucleosis that presented with cholestatasis, and summarize 23 cases from the literature to categorize this increasingly recognized clinical spectrum of EBV infection induced cholestatic hepatitis. METHODS:: We conducted an extensive literature review of all cases of EBV in pediatric and adult literature with cholestatasis using MEDLINE and EMBASE. We also included information on one case from our institution. RESULTS:: We identified 24 cases. Median age was 20 years (range 1-72 years), with 14 (58%) females. On presentation, fever (72%), jaundice (67%) and splenomegaly (62%) were the most common signs. Laboratory data revealed the median asparate aminotransferase (AST), or alanine aminotransferase (ALT) level was 179IU/L (range 56-2518IU/L), median serum bilirubin level 12.6mg/dL (range 2.2-47.5mg/dL) and median alkaline phosphatase level 749IU/L (range 31-3105IU/L). Diagnosis was confirmed using EBV viral capsid antigen IgM in 20 (83%) patients. HIV testing was done in 7 (29%) of the cases, and was negative. One patient died from the illness, while full recovery was reported in all other cases, with median follow-up of 30 days (range 5-180 days). CONCLUSIONS:: Cholestatasis is associated with EBV infection, and should be part of the differential diagnosis in all age groups, presenting with hyperbilirubinemia.     

Salmonella hepatitis

Typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. There have been more than 150 cases of salmonella hepatitis reported from both developed and developing countries. The documented incidence varies widely from less than 1% to 26% of patients with enteric fever. The possible associated factors for development of salmonella hepatitis are virulence of the organisms, delayed treatment and poor general health of the patients. The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial and includes endotoxin, local inflammatory and/or host immune reactions. Clinical jaundice in salmonella hepatitis usually occurs within the first 2 weeks of the febrile illness. Hepatomegaly and moderate elevation of transaminase levels are common findings. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis. A positive culture for salmonella from blood or stool is essential to differentiate salmonella hepatitis from other causes of acute hepatitis. Hepatic pathology is characterized by the presence of typhoid nodules with marked hyperplasia of reticuloendothelial cells. The prognosis is usually good as salmonella hepatitis responds well to a specific antibiotic therapy and jaundice resolves with clinical improvement. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of salmonella infection. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance.     

De novo autoimmune hepatitis in liver transplant: State-of-the-art review

In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necroinflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of nonorgan specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management.     

Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558AT) in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase. Acute and chronic liver diseases with viral, metabolic and autoimmune etiology were excluded. Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance. Liver biopsy showed: Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment, Kupffer's cell activation/hyperplasia and preserved biliary ducts. Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria, ATP8B1 and ABCB11 gene analysis was performed. Surprisingly, we found a novel nonsense variant of ATP8B1 gene(c.1558AT) in heterozygosis. The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance. Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6~(th) and 12~(th) mo.CONCLUSION A genetic abnormality, different from those already known, could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition, thus encouraging further mutation detection in this field.     

Hepatitis due to Epstein–Barr virus and cytomegalovirus: clinical features and outcomes

Objective: To determine the frequency of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes.

Methods: A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006–2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records.

Result: Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain–Barré syndrome following the infection.

Conclusion: A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.     

CASE REPORT: Vanishing Bile Duct Syndrome Associated with Chronic EBV Infection

We reported here an adult patient with vanishing bile duct syndrome due to chronic EBV infection. A 22-year-old male was admitted to a nearby hospital complaining of a sore throat and jaundice. He received a high dose of prednisolone for bile stasis of acute viral hepatitis. However, the hepatitis did not improve, and he was transferred to our hospital. He had exhibited jaundice for one year as well as hemophagocytic syndrome and intestinal perforation. Subtotal intestinal resection was successfully performed. Three follow-up biopsied liver specimens indicated vanishing bile duct syndrome. Positive results of EBV-DNA in his serum and mRNA of EBV by in situ hybridization of his liver indicated that massive doses of prednisolone caused chronic EBV infection and vanishing bile duct syndrome.     

A case of carbimazole-induced intrahepatic cholestasis. An immune-mediated reaction?

A patient is described with cholestatic hepatitis following the use of carbimazole. A liver biopsy specimen showed intracanalicular cholestasis and some mononuclear cell infiltrate in the portal triades, consistent with drug toxicity; indications of an autoimmune or viral pathogenesis were absent. Rechallenge with the drug precipitated jaundice and disturbed liver function once more. Carbimazole induced a blastogenic response of patient lymphocytes in vitro. Both may suggest the involvement of an immune-mediated reaction, especially as it has been shown that sensitized lymphocytes may produce a cholestatic factor on stimulation with antigen.