Successfully treated sulphasalazine-Induced fulminant hepatic failure, Thrombocytopenia and Erythroid Hypoplasia with intravenous immunoglobulin

We report the simultaneous development of fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia in a child treated with sulphasalazine. A 12-year-old girl with juvenile rheumatoid arthritis developed fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia, which was confirmed by liver histology and bone marrow examination, 2 weeks after initiation of sulphasalazine therapy. The patient recovered after administration of high doses of intravenous immunoglobulin. this is the first reported case of the concurrent development of these complications associated with sulphasalazine hypersensitivity. The use of intravenous immunoglobulin may have helped in the treatment of this rare adverse effect of sulphasalazine.     

Intensive therapy for fulminant hepatic failure: importance of co-operation between physicians of internal medicine and transplantation surgery]

We followed up the patients with fulminant hepatic failure who admitted in our hospital and investigated clinical problems raised in the patients who underwent living-related liver transplantation (LRLT). Among 15 patients with fulminant hepatic failure 6 were managed without LRLT and 3 patients survived, and the survival rate was 50%. Other 9 patients received LRLT, and 2 of these 9 died with their complications after the transplantation. Thus the survival rate by LRLT in fulminant hepatic failure was 77.8%. Brain CT scan examination showed severe brain edema in a patient and the edema did not improve after LRLT. Another patient suffered from development of fungal infection in her lungs after LRLT. We suspected the presence of subclinical infection in the preoperation period. The recovery from brain edema and the existence of subclinical infection are mostly difficult to evaluate but are very important for obtaining a good output. These results suggest that LRLT is a promising procedure for treatment of fulminant hepatic failure but a close cooperation between physicians of internal medicine and transplantation surgery from preoperative management until postoperative period is necessary.     

Fulminant liver failure induced by hepatosplenic alphabeta T-cell lymphoma

Since survival rates of fulminant liver failure are low, early consideration of liver transplantation in patients developing hepatic encephalopathy due to progressive liver failure is mandatory. Rapid diagnostic work-up is necessary to identify the underlying disease and to rule out contraindications to liver transplantation. We report the case of a 35-year-old patient presenting with fulminant hepatitis and a four-week history of biopsy-proven autoimmune hepatitis. Despite high-dose steroid-treatment liver function progressively worsened and hepatic encephalopathy rapidly developed. Histopathologic evaluation of a liver biopsy specimen revealed necrotizing hepatitis and rare atypical lymphocytes. Surgical biopsy specimens confirmed the suspicion of an aggressive hepatosplenic alphabeta T-cell lymphoma which represents a contraindication to liver transplantation.     

Acute pancreatitis caused by salazopyrine. An unusual association]

A 28 year old patient with a moderate attack of ulcerative colitis was treated with sulfasalazine. Ten days after, the patient was admitted with clinical and laboratory symptoms of acute pancreatitis (serum amylase 631 u., serum lipase 1080 u. urine amylase, 910 u.). Upon recovery, sulfasalazine was reintroduced at lower dosage (2 Gm/day), and the patient repeated the clinical and biological picture of acute pancreatitis (serum amylase of 710 and lipase 1010 u.) CAT scan showed pancreatic edema and ultrasonography demonstrated a normal gallbladder. The symptoms and laboratory abnormalities disappeared in three days after stopping sulfasalazine. The patient has been followed-up for one year without recurrence of pancreatitis on maintenance treatment with 1.5 Gm 5-Aminosalicylic acid.     

Late recurrence of fulminant myocarditis related to HSS/DRESS

Hypersensitivity Syndrome or Drug Reaction with Eosinophilia and Systemic Symptoms (HSS/DRESS) is a rare pharmacological hypersensitivity reaction that may include cardiac involvement, with high mortality and long-term heart failure.A 28-year-old woman, two months after the diagnosis of DRESS secondary to sulfasalazine, developed fulminant eosinophilic necrotizing myocarditis. After intensive multiorgan support, recovery and cardiac function normalization were observed. Eight months later presented a recurrence with fast progression to refractory cardiogenic shock and death.We alert to a rare and underdiagnosed pathology, with adverse prognosis, needing timely identification and treatment.     

Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis

In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p < 0.001). By 24 hours, 13 of 15 with organ failure versus 36 of 104 without organ failure met one or the other criterion (p < 0.001). The negative predictive value by 24 hours was 96% for necrotizing pancreatitis and 97% for organ failure. Hemoconcentration with an admission hematocrit > or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.     

Role of phospholipase A2 in human acute pancreatitis

In a prospective clinical trial, 85 patients with acute pancreatitis, including 50 with acute interstitial-edematous pancreatitis and 35 with necrotizing pancreatitis, were recruited. Serum pancreatic immunoreactive phospholipase A2 (IR-PLA2), serum phospholipase A catalytic activity (CA-PLA), and serum phospholipase A2 catalytic activity (CA-PLA2) were determined daily between day 1 and day 10 after the onset of the disease. The serum course of IR-PLA2 values for patients with acute interstitial-edematous pancreatitis was comparable to that for patients with necrotizing pancreatitis. In contrast, the determination of CA-PLA and of CA-PLA2 specific activity in the serum revealed a high differentiation between patients with interstitial edematous and those with necrotizing pancreatitis. The overall accuracy for differentiating patients with necrotizing pancreatitis from those with the interstitial-edematous type was 79% for CA-PLA and 77% for CA-PLA2 (cut-off level: CA-PLA, 15 U/L, day 1-5; CA-PLA2, 3.5 U/L, day 1-5). Patients with pancreatitis-associated pulmonary complications showed significantly higher CA-PLA and CA-PLA2 values in the serum. This study demonstrates the role of serum catalytic phospholipase A2 in human acute pancreatitis where the development of pancreatic necrosis and pulmonary failure is concerned.     

Hemoconcentration as an early risk factor for necrotizing pancreatitis

Objective: The aim of our study was to determine whether measurement of serum hematocrit during the first 24 h helps in distinguishing necrotizing from mild pancreatitis.
Methods: From May 1992 to June 1996, a case-control study was performed with cases of patients with necrotizing pancreatitis. We selected as a control the next patient admitted with mild pancreatitis.
Results: There were 32 patients in each group. Logistic regression identified an admission hematocrit of  ≥ 47%  and a failure of admission hematocrit to decrease at 24 h as the best binary risk factors for necrotizing pancreatitis. At admission, more patients with necrotizing pancreatitis than with mild pancreatitis had a hematocrit  ≥ 47%  (11/32 vs 3/32;   p = 0.03  ). At 24 h, 15 additional patients with necrotizing pancreatitis versus only one with mild pancreatitis showed no decrease in admission hematocrit (   p < 0.01  ). Thus, by 24 h, 26 of 32 patients with necrotizing pancreatitis versus only four of 32 patients with mild pancreatitis met one or the other criterion (   p < 0.01  ). The sensitivity and specificity at admission were 34% and 91%; at 24 h, 81% and 88%.
Conclusions: Hemoconcentration with an admission hematocrit  ≥ 47%  or failure of admission hematocrit to decrease at approximately 24 h were strong risk factors for the development of pancreatic necrosis.     

Fatal Massive Hepatic Necrosis: A Probable Hypersensitivity Reaction to Sulfasalazine

Sulfasalazine (salicylazosulfapyridine) is a commonly prescribed oral medication for inflammatory bowel disease. We report a case of a 15-yr-old boy with ulcerative colitis who developed a generalized hypersensitivity reaction with a serum sickness-like syndrome and severe hepatotoxicity while taking sulfasalazine, perphenazine, and amitriptyline. The injury to the liver persisted for 5 months after withdrawal of the drugs, and the patient died of terminal hepatic failure with massive hepatic necrosis. Severe hepatic toxicity to sulfasalazine is uncommon, but it can be fatal.     

A case of fulminant hepatic failure secondary to congestive heart failure

It has been generally accepted that congestive heart failure does not lead to fulminant hepatic failure, unless it is associated with cardiac shock or low cardiac output. Only three cases have been reported, in which liver congestion is followed by fulminant hepatic failure without a history of shock or low cardiac output. Here we present a case of a 48-year-old man with dilated cardiomyopathy and pulmonary infarction, who developed fulminant hepatic failure from congestion. When he was admitted for the control of diabetes mellitus, hepatomegaly of 3-finger breadth and marked cardiomegaly without pulmonary congestion was noted. Diabetes was controlled using insulin. But 3 weeks after admission, he sometimes complained of back dullness because of pulmonary infarction. His heart gradually increased in size, and Jugular venous dilatation and pretibial pitting edema also worsened. Jaundice was noted and serum GOT and GPT increased. A large liver of 6-finger breath below the right costal margin was able to be felt. But within one week, the size of the liver markedly decreased and the signs of hepatic failure such as jaundice, hepatic encephalopathy and numerous petechiae appeared. Blood pressure was maintained and no hypotension or cardiac shock was noted. The patient died of fulminant hepatic failure on the 20th days after onset of the hepatic failure. The autopsy revealed liver atrophy with severe central lobular necrosis, and thrombus in the right main pulmonary artery which caused severe pulmonary infarction. The mechanism of fulminant hepatic failure not accompanied with low cardiac output is discussed.     

Successful treatment of hyperthyroidism with amiodarone in a patient with propylthiouracil-induced acute hepatic failure.

Acute hepatic failure is a rare and potentially lethal complication of propylthiouracil (PTU) use for hyperthyroidism. We present a 20-year-old woman with Basedow-Graves' disease who developed PTU-induced fulminant hepatitis, which progressed to acute hepatic failure with grade III hepatic encephalopathy. Laboratory evaluation ruled out the most common causes of fulminant hepatitis. We treated her hyperthyroidism with amiodarone (average daily dose, 200 mg) for 3 weeks, achieving rapid and persistent euthyroidism, (triiodothyronine [T(3)] levels ranged between 64 and 109 ng/dL) without side effects. Amiodarone treatment did not abolish the thyroid radioactive iodine uptake (RAIU), allowing for subsequent treatment with radioactive iodine. The clinical course was favorable and the patient achieved full hepatic recovery 3 months after the hepatic failure was detected. After an extensive review of the literature, we believe that this is the first communication of the successful use of amiodarone to control hyperthyroidism in a patient with PTU-induced fulminant hepatitis.     

Albumin dialysis: effective removal of copper in a patient with fulminant Wilson disease and successful bridging to liver transplantation: a new possibility for the elimination of protein-bound toxins

BACKGROUND: Acute liver failure may be the first manifestation of Wilson disease. If copper elimination fails, liver transplantation is the only remaining therapeutic option. Albumin dialysis, a new method for the removal of protein-bound toxins, was performed in a patient with fulminant Wilson disease. METHODS: An 18-year-old man with Wilson disease presented with hyperacute liver failure, hepatic encephalopathy III, oligo-anuric renal failure, haemolytic anaemia, rhabdomyolysis, pancreatitis and thrombocytopenia. He was treated with albumin dialysis using a 44 g/l albumin-containing dialysate and a slow dialysate flow rate (1-2 l/h). The other details of the technique used are similar to routine continuous veno-venous haemodiafiltration. RESULTS: One hundred and five milligrams of copper were removed by albumin dialysis within the first six treatments, resulting in normalisation of blood-copper levels. Successful treatment of the multiorgan failure was achieved. Hepatic encephalopathy improved within 2 days. The patient initially refused liver transplantation. Therefore 35 additional albumin dialysis treatments were performed. Forty-three grams of bilirubin (an indicator of detoxified substances in the liver) and 196 mg of copper were removed. Multiorgan failure, in particular hepatic encephalopathy, did not recur during 59 days of treatment. Eventually, the patient agreed to liver transplantation and that was successful. CONCLUSION: Albumin dialysis is a new method for the effective treatment of fulminant Wilson disease, resulting in the removal of protein-bound toxins copper and bilirubin. It may serve as a new treatment option in hyperacute liver failure of other origin, acting as an extracorporeal detoxifier.     

Pancreatitis after rectal administration of 5-aminosalicylic acid

A patient treated with sulfasalazine for new-onset ulcerative colitis developed self-limited pancreatitis. Rechallenge with 5-aminosalicylic acid (5-ASA) in enema form (Rowasa) again induced pancreatitis. Recent case reports suggest that the salicylate component of sulfasalazine can lead to the development of pancreatitis with oral 5-ASA administration. This patient's course demonstrates further that rechallenge with 5-ASA in a rectal form may also lead to pancreatitis.     

Acute Pancreatitis Associated with Acute Hepatitis A

The etiology of acute pancreatitis is diverse, and unusual causes include several common viral infections. Although pancreatitis has been found at autopsy in patients with fulminant hepatic failure, there have been only a few reports of an association between mild to moderate acute viral hepatitis and acute pancreatitis. A case of acute hepatitis A complicated by acute pancreatitis is presented, and the relevant literature regarding this unusual association is reviewed.     

Increased serum and hepatic tissue levels of interleukin-18 in patients with fulminant hepatic failure

BACKGROUND: Fulminant hepatic failure is a serious clinical condition associated with a high mortality rate. Interleukin (IL)-18 is a pro-inflammatory cytokine that is associated with several inflammatory diseases. The purpose of the present paper was therefore to investigate whether IL-18 is elevated in patients with fulminant hepatic failure. METHODS: Serum levels of IL-18 were measured in patients with fulminant hepatic failure before and after liver transplantation. Native liver tissue samples were collected and the tissue levels of IL-18 were determined. Liver tissues were stained immunohistochemically with antihuman IL-18 antibody. The serum levels of IL-1beta, IL-6, IL-8, IL-12, interferon-gamma, and tumor necrosis factor-alpha were also determined in patients with fulminant hepatic failure before and after liver transplantation. RESULTS: Elevated levels of IL-18 in serum and hepatic tissue were observed in patients with fulminant hepatic failure. Native liver tissue samples were immunohistochemically positive for IL-18. Interleukin-18 levels were markedly reduced after liver replacement. No other inflammatory cytokines were substantially elevated in patients with fulminant hepatic failure. CONCLUSION: The serum levels of IL-18 levels are elevated much more than those of other cytokines in patients with fulminant hepatic failure.     

猪急性肝衰竭模型的建立及猪纤维介素的表达

目的 建立一个模拟人类疾病进程的猪急性肝衰竭(ALF)模型,用于ALF治疗药物的临床前安全性评价及疗效评价,检测模型中猪纤维介素(pfg12)的表达情况,为针对fg12的基因治疗提供基础和依据. 方法造模组耳静脉快速注射D-氨基半乳糖盐酸盐,剂量1.2 g/kg;对照组耳静脉快速注射5%的葡萄糖,剂量12 ml/kg.观察两组动物临床表现,肝功能指标和肝组织病理学改变,实时定量PCR检测肝组织中pfg12 mRNA表达,免疫组织化学检测肝组织中pfg12蛋白的表达.采用重复测量数据的方差分析和独立样本t检验进行统计学处理.结果 成功建立了与人在临床表现、肝脏生物化学指标、组织病理学改变相似的猪ALF模型;实时定量PCR检测结果显示造模组猪肝组织中pfg12的mRNA表达水平显著增加,与对照组比较,差异具有统计学意义(t=7.695,P＜0.05).免疫组织化学显示造模组猪肝组织中有明显的pfg12蛋白的表达,主要分布在肝细胞坏死区域的肝细胞、炎症浸润细胞、肝血窦内皮细胞及血管内皮细胞,对照组动物肝组织未见pfg12阳性着色.结论 以D-氨基半乳糖盐酸盐诱导的猪ALF模型可用于评价肝衰竭治疗药物的临床前疗效及安全性;pfg12在猪ALF动物模型的肝组织中异常高表达,提示其参与了ALF时肝细胞坏死的发生和发展过程.     

猪急性肝衰竭模型的建立及猪纤维介素的表达

目的 建立一个模拟人类疾病进程的猪急性肝衰竭(ALF)模型,用于ALF治疗药物的临床前安全性评价及疗效评价,检测模型中猪纤维介素(pfg12)的表达情况,为针对fg12的基因治疗提供基础和依据. 方法造模组耳静脉快速注射D-氨基半乳糖盐酸盐,剂量1.2 g/kg;对照组耳静脉快速注射5%的葡萄糖,剂量12 ml/kg.观察两组动物临床表现,肝功能指标和肝组织病理学改变,实时定量PCR检测肝组织中pfg12 mRNA表达,免疫组织化学检测肝组织中pfg12蛋白的表达.采用重复测量数据的方差分析和独立样本t检验进行统计学处理.结果 成功建立了与人在临床表现、肝脏生物化学指标、组织病理学改变相似的猪ALF模型;实时定量PCR检测结果显示造模组猪肝组织中pfg12的mRNA表达水平显著增加,与对照组比较,差异具有统计学意义(t=7.695,P＜0.05).免疫组织化学显示造模组猪肝组织中有明显的pfg12蛋白的表达,主要分布在肝细胞坏死区域的肝细胞、炎症浸润细胞、肝血窦内皮细胞及血管内皮细胞,对照组动物肝组织未见pfg12阳性着色.结论 以D-氨基半乳糖盐酸盐诱导的猪ALF模型可用于评价肝衰竭治疗药物的临床前疗效及安全性;pfg12在猪ALF动物模型的肝组织中异常高表达,提示其参与了ALF时肝细胞坏死的发生和发展过程.     

Extreme lymphoplasmacytosis and hepatic failure associated with sulfasalazine hypersensitivity reaction and a concurrent EBV infection—case report and review of the literature

We present an unusual case of a patient with extreme lymphoplasmacytosis and hepatic failure in association with a reaction to sulfasalazine and a concurrent Epstein-Barr virus (EBV) infection. Sulfa drugs can cause a wide range of allergic and hypersensitivity reactions and occasionally can lead to a fulminant illness. In the case under discussion the patient had hepatotoxicity, skin rash, fever, and peripheral blood atypical lymphocytosis. Initial impressions suggested the possibility of a malignant lymphoproliferative disorder. Flow cytometry of peripheral blood and a bone marrow biopsy provided clear evidence for a reactive, polyclonal process as opposed to a malignant disorder. Cessation of the offending drug and administration of steroids led to dramatic improvement. This case illustrates that drug hypersensitivity reactions can be manifested by an extreme lymphocytoid leukemoid reaction.     

Potentiation of Acetaminophen Hepatotoxicity by Phenytoin,Leading to Liver Transplantation

We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the “nontoxic” range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.     

Surgical treatment of acute pancreatitis

Opinion statement Patients with predicted severe necrotizing pancreatitis as diagnosed by C-reactive protein (>150 mg/L) and/or contrast-enhanced computed tomography should be managed in the intensive care unit. Prophylactic broad-spectrum antibiotics reduce infection rates and survival in severe necrotizing pancreatitis. Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy is a causative therapy for gallstone pancreatitis with impacted stones, biliary sepsis, or obstructive jaundice. Fine needle aspiration for bacteriology should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome. Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for surgery. Patients with sterile pancreatic necrosis should be managed conservatively. Surgery in patients with sterile necrosis may be indicated in cases of persistent necrotizing pancreatitis and in the rare cases of “fulminant acute pancreatitis.” Early surgery, within 14 days after onset of the disease, is not recommended in patients with necrotizing pancreatitis. The surgical approach should be organ-preserving (debridement/necrosectomy) and combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate. Minimally invasive surgical procedures have to be regarded as an experimental approach and should be restricted to controlled trials. Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis.