Fatal Hepatic Coma Complicating Oxymetholone Therapy in Multiple Myeloma

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma. G. P. Young, P. S. Bhathal, J. R. Sullivan, A. J. Wall, D. J. Fone and T. H. Hurley, Aust. N.Z. J. Med, 1977,7, pp. 47–51. Two patients with multiple myeloma died in acute liver failure. Both had been treated with the anabolic steroid oxymetholone and both subsequently developed severe cholestatic hepatitis. In one the histological lesion progressed despite cessation of oxymetholone therapy. Myeloma infiltration of the liver and peliosis hepatis were not seen. As a fatal outcome from cholestatic hepatitis due to oxymetholone is rare it is possible that an unknown potentiating factor is present in multiple myeloma that can lead to a fatal outcome. If oxymetholone therapy is to be used in such patients then close clinical and laboratory assessment of liver function should be carried out in an attempt to prevent this unusual and fatal complication.     

Severe acute cholestatic hepatitis by infiltration of monoclonal plasma cells in multiple myeloma

BACKGROUND: Plasma cell infiltration of the liver can be detected in 25 to 40% of patients with multiple myeloma. However, there are only rare cases of multiple myeloma clinically presenting as acute liver disease. CASE REPORT: We report an 88-year-old woman with painless jaundice and abnormal liver function tests, resembling acute cholestatic hepatitis. Viral hepatitis as well as autoimmune hepatitis could be excluded. Liver biopsy revealed a diffuse portal and sinusoidal infiltration of plasma cells with lambda light chain restriction. Serological immune fixation disclosed monoclonal gammopathy of IgG lambda with bone marrow infiltration of 25% plasma cells. After administration of 60 mg prednisolone per day, the elevated liver enzymes declined considerably. CONCLUSION: Hepatic plasma cell infiltration of multiple myeloma can, in rare cases, manifest as acute cholestatic hepatitis, which may respond to treatment with corticosteroids.     

Hepatocellular carcinoma associated with anabolic steroid therapy: Report of a case and review of the Japanese literature

We report herein the case of a 35-year-old woman with aplastic anemia who developed hepatocellular carcinoma after long-term therapy with oxymetholone. She was treated with 60mg/day of oxymetholone for 3 years (total dose 64.8g). Alphafetoprotein, hepatitis B surface antigen, and hepatitis C antibody were all negative, but serum titers of carcinoembryonic antigen and carbohydrate antigen were elevated. Lateral segmentectomy of the liver was performed. The histopathological findings were compatible with those of multiple hepatocellular carcinoma without liver cirrhosis. Three years since the operation, the patient is doing well and no signs of tumor recurrence have been detected. According to our review of Japanese cases of hepatocellular carcinoma associated with anabolic steroid therapy, in all instances the tumors developed after long-term administration of anabolic steroids for hematologic diseases. In patients under long-term anabolic steroid therapy, routine screening of the liver by ultrasonography and computed tomography should be performed to detect liver tumors in the early stages.     

Hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis

A case of hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis is described. The patient was admitted with symptoms of hepatitis with cholestatic jaundice. Antibody tests for hepatitis B and C and human immunodeficiency virus were negative. The patient continued to deteriorate clinically. Eventually, the patient succumbed to hepatic failure. Autopsy disclosed systemic cryptococcosis that caused extensive necrosis of the liver. In review of the literature, only nine cases of cryptococcal infection presenting as hepatitis, cholangitis, and cholecystitis as initial manifestation were reported. Four of these patients had been subjected to exploratory laparotomy for clinical suspicion of acute abdomen. One patient developed cirrhosis as a result of cryptococcal hepatitis. Two patients succumbed to hepatic failure. Cryptococcosis is known to occur commonly in immunocompromised patients, yet only two reported cases presenting as hepatitis were associated with immunocompromised status.     

Case Report: Severe cholestatic jaundice induced by Epstein-Barr virus infection in the elderly

Infectious mononucleosis due to Epstein-Barr virus (EBV) is almost always a self-limited disease, most commonly seen in young adults. Hepatitis is a well-recognized complication of EBV infection that usually resolves spontaneously. Jaundice occasionally results from the unusual complication of autoimmune haemolytic anaemia rather than hepatitis. We report a 60-year-old man with severe cholestatic jaundice whose history, liver histology and laboratory findings suggested EBV infection. He also developed significant jaundice related to his hepatitis, but not to autoimmune haemolysis, a situation that led to diagnostic delay. Costly diagnostic laboratory tests and invasive procedures were performed to rule out a malignant extrahepatic biliary obstruction. Physicians need to be aware of this complication and EBV infection should be included in the differential diagnosis of cholestatic jaundice in the elderly.     

Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate

Background/Aims: Autoimmune hepatitis is a heterogeneous disorder that typically responds to glucocorticoids with or without azathioprine. Treatment options for patients not responding to standard therapy are limited.Methods: We describe a 52-year-old female who presented with jaundice, marked elevation in liver enzymes, positive antinuclear antibody and a liver biopsy consistent with autoimmune hepatitis. Liver enzymes did not normalize with prednisone alone. When azathioprine was added, the disease flared. The patient refused cyclosporine. Methotrexate 7.5 mg po per week resulted in normalization of liver enzymes, improved liver histology, and has maintained remission with a steroid-sparing effect.Results/Conclusion: In this patient methotrexate was used successfully to treat type 1 autoimmune hepatitis. This suggests that methotrexate may have a role in treatment of autoimmune hepatitis refractory to standard therapy.     

CHOLESTASIS IN ACUTE ALCOHOLIC LIVER DISEASE

10 of a series of 108 patients with alcoholic liver disease presented with cholestasis associated with non-cirrhotic alcoholic liver disease and without evidence of extrahepatic biliary obstruction. In 7 patients liver histology and the associated conditions presenting as cholestasis were heterogeneous. However, in 3 patients who had been drinking excessively before cholestatic jaundice developed, cholestasis was a major feature of liver histology. The term acute alcoholic cholestasis is suggested for this apparently distinct syndrome of cholestatic jaundice in the absence of hepatitis.     

Cholestatic hepatitis related to use of irbesartan: a case report and a literature review of angiotensin II antagonist-associated hepatotoxicity

We report a patient who developed cholestatic hepatitis shortly after starting therapy with irbesartan, one of the new, recently marketed angiotensin II antagonists. Serological studies and ultrasonography ruled out viral hepatitis and extrahepatic obstructive jaundice, respectively. A percutaneous liver biopsy showed a portal inflammatory infiltrate with eosinophils and marked cholestatic features in the perivenular area. Irbesartan was discontinued and the patient's jaundice resolved slowly over a period of several weeks, although mild biochemical cholestasis lasted for more than 1 year. There have been seven prior cases of angiotensin II antagonist-induced hepatotoxicity reported in the literature. A class warning for hepatotoxicity for these compounds should probably be considered.     

Fatal hepatic decompensation in a bone marrow transplant recipient with HBV-related cirrhosis following lamivudine withdrawal

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.     

Pazopanib-induced severe acute liver injury: A case report

Rationale:Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States. Painkillers and fever antipyretics are the most common cause of DILI. Hepatic injury can be provoked by DILI as hepatocellular or cholestatic type.Patient concerns:A 48-year-old woman presented jaundice accompanied by nausea and vomiting. The patient was an inactive hepatitis B carrier with low viral titer and was diagnosed renal cell carcinoma (RCC) with hepatic metastasis requiring pazopanib treatment. Prior to administration of pazopanib, tenofovir administration was started to prevent exacerbation of hepatitis B. The patient was referred to clinic of gastroenterology department due to sudden elevation of bilirubin after 5 weeks of pazopanib treatment.Diagnoses:Abdominal ultrasound and computed tomography showed non-specific finding other than metastatic nodule in the liver and liver cirrhosis. After then, the patient was performed liver biopsy, and the biopsy result was acute cholestatic hepatitis with centrilobular area necrosis and portal inflammation. Therefore, considering the clinical history and biopsy results, the patient was diagnosed as DILI due to pazopanib.Interventions:After the biopsy, empirical steroid therapy was initiated and after 7 weeks of pazopanib discontinuation.Outcomes:The total bilirubin level returned to normal from peak level of 24.61 to 1.52 mg/dL.Lessons:In patients with renal cell carcinoma, pazopanib treatment requires clinical caution as it causes rare complications such as severe jaundice and acute cholestatic hepatitis.     

Flucloxacillin induced delayed cholestatic hepatitis

We report four cases of severe delayed cholestatic hepatitis induced by flucloxacillin. All patients presented with deep jaundice and pruritus which developed soon after ceasing flucloxacillin. Liver function tests were abnormal in all patients with markedly elevated serum bilirubin concentration, alkaline phosphatase and aspartate transaminase levels. Extrahepatic biliary obstruction and infective hepatitis were excluded in all cases. Liver biopsies showed centrilobular cholestasis with portal and lobular inflammation and eosinophil infiltration. Although symptoms resolved within six weeks in all patients, cholestatic liver function tests have persisted in two patients for more than six months. With the increasing usage of this drug and the delayed presentation of cholestasis, flucloxacillin needs to be considered in the differential diagnosis of all patients presenting with cholestatic jaundice.     

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.     

Severe aplastic anaemia following hepatitis A

A 3-year-old child developed severe aplastic anaemia following hepatitis A. Since no HLA-compatible donor was available, he was treated with oxymetholone, antithymocytic globulin and methylprednisolone, but no haematologic recovery was observed and he consequently died of pneumonia. Although the association of aplastic anaemia and hepatitis A has already been recognized, this patient represents the first case of aplastic anaemia in which the previous hepatitis A has been well documented.     

Refractory hypocalcemia precipitated by dual infection with typhoid fever and hepatitis A in a patient with congenital hypoparathyroidism

We present this rare occurrence of a 17 yr old boy, a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures. Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels. Investigations revealed severe hypocalcaemia (3.2 mg/dL), low 25 hydroxyvitamin D levels and hypomagnesaemia. The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes. Microbiological investigations were confirmatory for both hepatitis A and typhoid fever. In spite of the aggressive management with intravenous calcium gluconate infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels. We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient.     

肾移植后纤维化淤胆性肝炎的临床病理特点

目的 探讨纤维化淤胆性肝炎（fibrosing cholestatic hepatitis,FCH)临床病理特点和拉米夫定的防治效果。方法 回顾性分析我院794例肾移植后发生的17例重度黄疸性肝炎，其中6例经肝活检证实，2例有发病前后组织病理对比。结果 肾移植者中慢性HBV感染者为9.3%，其中FCH发生率为22.9%，肝活检证实的6例发病时间在移植后的1.5-22个月中，2例经拉米夫定治疗后缓解，4例慢性乙肝患者移植前后服用拉米夫定未发生纤维化淤胆性肝炎，移植后应用极大剂量多种免疫抑制剂，逐渐发生淤胆性肝炎和迅速进展肝功能衰竭，血清HBVDNA达极高水平；组织学表现独特的病变组合；肝细胞广范围气球样变性，毛玻璃样肝细胞不少见，区域性肝细胞溶解消失，淤胆，而炎症浸润轻微，并由汇管区发展的广范围纤维化。结论 肾移植后可发生纤维化淤胆性肝炎，拉米夫定对FCH有明显的即时治疗效应。     

Changes in plasma high density lipoprotein cholesterol and phospholipid in acute viral hepatitis and cholestatic jaundice

Forty-four male and female subjects aged 22-57 years were studied. Thirteen patients had acute viral hepatitis, and eleven patients had cholestatic jaundice due to carcinoma of the head of the pancreas. Twenty healthy volunteers who served as controls were also included. In hepatitis patients, the mean plasma levels of total cholesterol (TC) and the high density lipoprotein (HDL)-phospholipid/phospholipid (HDLPL/PL) ratio were reduced, and HDL-cholesterol (HDLC), HDL-phospholipid (HDLPL) and the phospholipid/total cholesterol (PL/TC) ratio were normal, while total phospholipid (PL) levels and the HDLC/TC ratio were significantly increased compared to the control values. In patients with cholestatic jaundice the mean plasma total cholesterol, phospholipid and HDLC levels were elevated, and HDLPL/PL, HDLPL, HDLC/TC and PL/TC remained normal compared to the control values. A comparison within the patient groups showed that plasma TC, PL and HDLC levels were significantly increased in cholestatic jaundice when compared with the corresponding levels in hepatitis patients. The mean plasma levels of HDLPL, HDLC/TC and PL/TC did not show any significant variation within the patient groups. Alkaline phosphatase (ALP) correlated positively with TC, and total protein correlated negatively with TC and HDLPL, while albumin correlated negatively with TC, HDLC and HDLPL in cholestatic jaundice. Alanine amino-transferase (ALAT) also correlated positively with PL in cholestatic jaundice, while albumin correlated positively with TC in hepatitis. The results suggest that lipoproteins might be metabolized differently in these two forms of cholestasis.     

Cholestatic hepatitis induced by the amoxicillin-clavulanic acid combination. A case and review of the literature

We report the case of a patient who developed jaundice after receiving amoxicillin-clavulanic acid for 7 days. Laboratory features were consistent with acute cholestatic hepatitis. Histopathological examination of a liver specimen showed cholestasis. Complete recovery occurred within 2 months after withdrawal of the drug. Analysis of the 24 reported cases of amoxicillin-clavulanic acid induced hepatitis revealed a predominantly cholestatic syndrome occurring soon after drug administration. In all cases, hepatic dysfunction disappeared within 1 to 3 months after discontinuation of the drug. Because of the small number of cases in contrast with the widespread use of this drug, associated with blood hypereosinophilia or eosinophilic infiltration of portal triads in some cases, a hypersensitivity phenomenon is suggested.     

Cholestatic jaundice associated with D-penicillamine therapy

Cholestatic jaundice is a rare complication of penicillamine therapy. We report here a 35-year-old patient who developed fever, a rash and cholestatic jaundice 16 days after commencing treatment with penicillamine for cystinuria. The jaundice subsided slowly after discontinuation of the drug and with prolonged therapy with prednisone. The literature on penicillamine-induced liver injury is reviewed.     

CASE REPORT: Light Chain Deposition Disease of the Liver Without Renal Involvement in a Patient with Multiple Myeloma Related to Liver Failure and Rapid Fatal Outcome

We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie stage III) who developed jaundice and severe cholestasis after a first cure with systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound and CT scan showed mild hepatomegaly without evidence of extrahepatic or intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive amorphous substance. Immunohistochemistry showed positivity for kappa-light chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD immunoglobulins as well as for AA and AL proteins and for amyloid P component. A diagnosis of light chain deposition disease (LCDD) of the liver was made. The patient developed rapid deterioration of liver function, leading to a multisystem dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5% and myeloma is the underlying disease in two thirds of patients with LCDD. The kidneys are involved in almost all cases of LCDD and renal dysfunction usually reveals the disease. Only three patients with LCDD of the liver without overt renal involvement have been reported so far. This is the first observation of LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis of high tumor mass myeloma, without overt renal involvement, leading rapidly to the patient's death.