Mild Aminotransferase Elevation Research Articles

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.

MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2. (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.

Evaluation of the safety profile and therapeutic efficacy of remdesivir in children with SARS-CoV-2 infection – a single-center, retrospective, cohort study

Despite 3.5 years of the SARS-CoV-2 pandemic, we still lack effective drugs against COVID-19. The first and most widely used drug, remdesivir, has not yet been shown to be effective in adults. Even less is known about its effectiveness in children. Therefore, the aim of this retrospective study was to evaluate the safety and efficacy of remdesivir in pediatric patients with COVID-19 hospitalized in one medical center. The medical records of 328 children with COVID-19 were analyzed. Analysis was performed on the subgroups of children treated and not treated with remdesivir. Clinical data on general health, course of COVID-19 and treatment received were analyzed. Remdesivir was administered to 64 children, 16 to treat severe or critical illness and 48 because of the presence of risk factors to prevent progression to severe COVID-19. In children with severe COVID-19, remdesivir did not reduce the mortality rate. However, in patients with milder disease and risk factors, the drug significantly reduced the risk of progression to severe disease. Among adverse events, only mild aminotransferase elevations were observed in 4 patients, but none of these required discontinuation of treatment.Conclusions: Remdesivir is a safe treatment option for children with COVID-19. However, the efficacy of this therapy is still uncertain. It appears that in children with asymptomatic to moderate COVID-19 and risk factors for severe disease, remdesivir could be an effective method of prophylaxis. However, its efficacy in controlling severe disease is questionable and requires further study.What is Known:• There are still no effective drugs to combat COVID-19, and the efficacy of the widely used remdesivir in adults is controversial.• All recommendations and guidelines on the use of remdesivir in the pediatric population are based mainly on clinical trials in adults.What is New:• Remdesivir is a safe treatment for COVID-19 in the pediatric population.• In children with asymptomatic to moderate COVID-19 and risk factors for severe disease, remdesivir could be an effective drug to prevent disease progression. However, its efficacy in treating severe disease in children needs further exploration.

Unraveling the Molecular and Cellular Pathogenesis of COVID-19-Associated Liver Injury.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) continues to cause substantial morbidity and mortality. Most infections are mild; however, some patients experience severe and potentially fatal systemic inflammation, tissue damage, cytokine storm, and acute respiratory distress syndrome. Patients with chronic liver disease have been frequently affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes may be a risk factor for disease progression, even in the absence of underlying liver disease. While the respiratory tract is a primary target of SARS-CoV-2, it has become evident that COVID-19 is a multisystemic infectious disease. The hepatobiliary system might be influenced during COVID-19 infection, ranging from a mild elevation of aminotransferases to the development of autoimmune hepatitis and secondary sclerosing cholangitis. Furthermore, the virus can promote existing chronic liver diseases to liver failure and activate the autoimmune liver disease. Whether the direct cytopathic effects of the virus, host reaction, hypoxia, drugs, vaccination, or all these risk factors cause liver injury has not been clarified to a large extent in COVID-19. This review article discussed the molecular and cellular mechanisms involved in the pathogenesis of SARS-CoV-2 virus-associated liver injury and highlighted the emerging role of liver sinusoidal epithelial cells (LSECs) in virus-related liver damage.

Wilson – Konovalov Disease: Clinical Cases with Different Manifestations and Outcomes

Аim: to describe clinical cases of Wilson – Konovalov disease in pediatric patients.Key points. The first clinical case demonstrates the manifestation of Wilson – Konovalov disease with unexplained mild elevation of aminotransferases at the age of 6 years. Despite the persistent hyperenzymemia, no additional laboratory tests were prescribed. At the age of 10, the patient showed signs of liver failure and neurological symptoms. Laboratory and instrumental examination enabled to diagnose Wilson – Konovalov disease at the stage of liver cirrhosis. The diagnosis was confirmed at the Federal medical center. The diagnosis was delayed and made 4 years after the hyperenzymemia was first revealed. The relief of clinical signs was observed after the orthotopic transplantation of the right lobe of the liver from a living related donor. The patient was under surveillance for 10 years after the transplantation.The second clinical case shows another variant of the course of the Wilson – Konovalov disease manifested as an acute hepatitis. To clarify the etiology of the disease, the patient was hospitalized. In 2 weeks, the patient developed symptoms of acute liver failure, progressive hemorrhagic syndrome, acute hepatic encephalopathy. Death from fulminant hepatitis occurred in 3 weeks after the disease onset after the disease onset.Conclusion. Healthcare workers should be aware of clinical signs of Wilson – Konovalov disease. Screening for the disease is recommended for children with an unexplained increase of liver transaminases, acute liver failure, chronic hepatitis and liver cirrhosis.

Fontan-associated liver disease.

Fontan-associated liver disease.

Liver injury caused by fenofibrate within 48\xa0h after first administration: a case report

BackgroundFenofibrate is commonly used in the treatment of dyslipidemia. Fenofibrate is related to mild aminotransferase elevations and in some cases severe chronic injury such as fibrosis or cirrhosis, resulting in liver transplantation or death. The latency of disease has been reported to range between weeks to years.Case presentationA 63 years old male with hypertriglyceridemia developed symptoms of fatigue and anorexia 48 h after taking fenofibrate for the first time. The patient’s aminotransferase level was more than 10 times ULN. Immediately, fenofibrate was discontinued and aminotransferase level returned to normal 23 days later. To assess causality between the drug and liver damage, the standardized Roussel Uclaf Causality Assessment Method (RUCAM) was used. The patient's RUCAM score was 7, which fell in the group of “probable”. Eight months later, follow-up examination suggested the liver function was normal.ConclusionsWeakness, fatigue and abnormal liver function during fenofibrate therapy should be closely monitored and trigger prompt withdrawal if these symptoms occur.

Can atypical antipsychotic drugs cause hepatotoxicity?

IntroductionNeuropsychiatric drugs account for 16% of drugs that can lead to hepatotoxicity and psychiatric patients can have multiple comorbidities that can increase the incidence of liver disorders such as alcoholism, drug abuse and polymedication. The continuous use of atypical antipsychotic drugs (AAD) has raised questions over their tolerability over endocrine, metabolic and cardiovascular systems. They are also associated with mild elevation of aminotransferases and occasionally cause idiosyncratic liver injury with varying phenotypes. Hepatotoxicity is defined based on biological parameters such as elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT or clinical abnormalities (jaundice and hepatitis).ObjectivesThis work reviewed the current available evidence on the hepatic damage produced by AAD.MethodsNon-systematic review of the literature with selection of scientific articles published in the past 10 years; by searching Pubmed and Medscape databases using the combination of MeSH descriptors. The following MeSH terms were used: atypical antipsychotic drugs; hepatotoxicity; hepatic; Olanzapine; Clozapine; Risperidone; Aripiprazol; Paliperidone.ResultsAtypical Antipsychotic Drugs are generally well tolerated and hepatic alterations are in general very low or rare. The cases published were observed with Clozapine, Olanzapine and Risperidone. Atypical Antipsychotic drugs have a better profile than Chlorpromazine.ConclusionsIn conclusion, the hepatic injury generally occurs within the first weeks of treatment and is usually reversible with drug withdrawal. Hepatic check-ups may be relevant, especially in the beginning of treatment.DisclosureNo significant relationships.

2259 Severely Jaundiced Body Builder: A Case of Acute Cholestatic Syndrome With Anabolic Androgenic Steroid Use

INTRODUCTION: Illicit use of anabolic androgenic steroids (AAS) has been growing among athletes and bodybuilders for cosmetic and performance purposes. We report a case of one of the possible hepatic complications of AAS, acute cholestatic syndrome (ACS), in a male with anabolic steroid abuse. CASE DESCRIPTION/METHODS: 27-year-old Polish man with no past medical history presented with jaundice, itching of the body, dark-colored urine, clay-colored stools for 5 weeks. No abdominal pain was reported. Patient reported taking for 4 months 4 types of AAS (testosterone, oxandrolone, methasterone and trenbolone) for body building, which he stopped taking 6 weeks prior to initial presentation due to fatigue. Vitals were normal, and on exam he appeared to be a muscular, jaundiced male with scratch marks on his skin. Abdominal exam revealed a non-tender, non-distended abdomen, with difficulty palpating the liver edge due to the muscularity. Laboratory tests were significant for total bilirubin of 34.8 mg/dL with direct of 23.5 mg/dL, AST 55 U/L, ALT 70 U/L, ALP 212 U/L, GGT 57 U/L, INR 1, creatinine 1.1 mg/dL. Liver ultrasound showed hepatomegaly with no biliary dilation and patent hepatic and portal veins. A liver biopsy was obtained showing portal neutrophil predominant inflammation with occasional eosinophils, mild portal fibrosis and cholestasis, suggestive of drug-induced hepatotoxicity. Liver function tests normalized after 4 months of cessation of AAS use, with resolution of his jaundice and pruritis. DISCUSSION: Body builders usually prefer polydrug use of AAS to maximize the desired effects and hypothetically reduce side effects at the same time. But contrary to their belief, the concomitant use of different illicit AAS may be a factor in their toxicity, making difficult to link an adverse effect with a specific substance. Acute cholesta tic syndrome, has been associated with use of the 17α – alkylated anabolic steroids ( i.e. oxandrolone, methasterone), thought related to an increase of reactive oxygen. This leads to prolonged direct toxic effects and intrahepatic cholestasis, though the pathophysiology remains unclear. ACS usually occurs 1-4 months after steroid initiation presenting with nausea, fatigue, pruritis; later, jaundice, dark urine, with significantly elevated total bilirubin and ALP but mild aminotransferase elevation can be seen. Management consists of stopping anabolic steroid use, supportive care and symptomatic treatment of pruritis.

Liver function assessment using indocyanine green plasma disappearance rate in a young male with icteric leptospirosis: a case report

BackgroundLeptospirosis is one of the leading global zoonotic causes of morbidity and mortality. It is induced by a pathogenic spirochete of the genus Leptospira. The icteric form of leptospirosis is characterized by pronounced hyperbilirubinemia and associated with significantly increased mortality. Conventional static liver function tests insufficiently assess hepatic damage and have limited prognostic value. Dynamic tests, such as indocyanine green plasma (ICG) clearance, more adequately reflect hepatic functional status. In this case report we describe the ICG plasma disappearance rates (ICG-PDR) in a patient with leptospirosis and massive hyperbilirubinemia, expanding our knowledge of liver dysfunction in icteric leptospirosis.Case presentationA 21-year-old Caucasian man presented with acute-onset jaundice, myalgia, fever and headaches. Laboratory tests upon admission revealed, most notably, acute kidney failure and hyperbilirubinemia of 17 mg/dl with mild elevation of aminotransferases. In the course of the following 4 days, total serum bilirubin increased to 54 mg/dl. The clinical outcome was favorable with intravenous ceftriaxone and doxycycline. Presumptive diagnosis of leptospirosis was later confirmed by PCR-based amplification of leptospiral DNA in the blood. ICG-PDR values, bilirubin as well as aminotransferases were recorded throughout hospitalization and a 3-month follow-up period. Initially dramatically reduced ICG-PDR (2.0%/min, normal range: 18–25%/min) rapidly normalized within 10 days, while bilirubin remained elevated up to week 7. Mild elevation of serum alanine aminotransferase was at its peak of 124 U/l by day 12 and reached close to normal levels by week 7 upon admission.ConclusionsMarkedly diminished ICG-PDR values presented in this case report suggest severe liver function impairment in the acute phase of icteric leptospirosis. Prolonged elevation of serum bilirubin may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis in addition to the static tests.

Drug-, herb- and dietary supplement-induced liver injury.

Drug- and substance-induced liver injury accounts for approximately 20% of pediatric cases of acute liver failure. It is caused by two mechanisms: direct and idiosyncratic hepatotoxicity. Direct hepatotoxicity is the result of the administration of a drug with intrinsic toxicity and is dose-dependent (e.g., acetaminophen). Idiosyncratic hepatotoxicity is unpredictable, uncommon, variable in presentation, and doseindependent. The clinical, histological, and laboratory manifestations include hepatitis, which is generally asymptomatic but with a significant increase of liver enzymes; cholestasis, accompanied with jaundice, pruritus, prominent elevation of alkaline phosphatase, and mild elevation of aminotransferases; or mixed, with elements of both hepatitis and cholestasis. Time to recovery is variable, depending on the type of liver injury. Early detection and discontinuation of the causative drug is the most effective and important step for the fast resolution of histological and clinical changes, thus reducing severe liver injury.

Clinico-etiological profile of raised aminotransferases in hospitalized children with liver disease and correlation with their severity level

Objective: The aim of this study was to analyze the clinico-etiological profile of raised aminotransferases in children with their severity level. Materials and Methods: We retrospectively analyzed 65 admitted children aged 1 month to 18 years with raised aminotransferases levels from January 2015 to July 2015. We divided them into three groups based on more liver specific, alanine aminotransferase (ALT) levels as mild (1-3 times of normal), moderate (3-20 times of normal), and severe if ALT ?20 times. Results: Total 65 children were retrospectively studied with a mean age of 72±52 months (range 1 month - 18 years), and male: Female ratio of 1.5/1. These patients were divided into three groups on the basis of their maximum ALT levels. Average levels of deranged ALT (mean±standard deviation) in mild, moderate, and severe groups were 78.8±27, 289±153, and 1938±861 IU/L, respectively. Out of 65 children, the clinical presentation was acute hepatitis in 35 (53%), acute liver failure in 15 (23%), acute on chronic liver failure in 7, and chronic liver disease in 8 patients. The etiologies were acute infective hepatitis in 41% (27) followed by metabolic in 15% (10), extra hepatic obstruction (7), autoimmune hepatitis (5), ischemic causes (7), neonatal hepatitis (2), hemophagocytic lymphohistiocytosis (HLH) (2), drug induced (2), cryptogenic (2), and diabetic ketoacidosis (1). Mild elevation of aminotransferases (n=17) was most commonly seen in metabolic liver disease (35%) followed by biliary tract obstruction (28%). Moderate elevation of aminotransferases levels (n=24) was seen in acute infective (29%) followed by metabolic liver disease (16%). In patients with severe elevations (n=24), the most common etiological diagnosis was acute infective hepatitis in (70%) followed by ischemic hepatitis (20%). The most common cause of acute infective hepatitis was acute viral hepatitis A. Conclusion: On the correlation of raised ALT with etiology, we suggest that severity grading of deranged aminotransferases can guide toward etiological diagnosis and narrow down the specific investigation required. Thus, it may help in early diagnosis and cost-effective management.

Assessment of Dengue fever severity through liver function tests.

To assess the utility of liver function tests (LFTs) for early recognition and prediction of severity of Dengue fever in hospitalized patients. An analytical study. Services Institute of Medical Science and Fatima Memorial Hospital, Lahore, from September - December 2010. Admitted cases of Dengue fever were divided into 3 groups; mild, moderate and severe increases in aminotransferases. Elevation in LFTs was co-related with good or bad outcome i.e. (survival or complication free stay) or (death or complications). RESULTS were analyzed in SPSS version 18. Out of the 353 patients with mean age of 37.12 ± 15.45 years, 245 (69.4%) were males and 108 (30.6%) were females. Seventy five patients (21.2%) had mild elevation of aminotransferases (2 fold increases), 265 patients (75.1%) had moderate increases (3 to 4 fold) and 13 (3.7%) had severe (> 4 fold increase). ALT was statistically higher in patients with septicemia, hepatic and renal failure (p-value ² 0.05). AST was higher in almost all complications. Prolonged hospital stay was associated with raised LFTs and greater complications and mortality. AST was found to be twice as much raised as ALT. AST and ALT were statistically higher in patients with worse outcome thus can lead to early recognition of high risk cases.

Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions.

The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management.

Biliary Ascariasis: A difficult extraction

AbstractHepatobiliary ascariasis (HBA) is a common complication of Ascaris infestation. It is reported mostly from developing countries. It is a common cause of biliary colic and cholangitis in some parts of India. It is also proposed as an etiology of a subset of patients with recurrent pyogenic cholangitis (RPC). Conservative management, endoscopic removal of the worm wherever needed and deworming is the accepted treatment approach. We herewith present a unique challenge that we encountered during worm removal. The patient was a 35-year-old female with 3 days history of epigastric pain, fever with rigors and vomiting. Her biochemical evaluation showed mild neutrophilic leukocytosis, mild elevation of aminotransferases and alkaline phosphatase. Ultrasound abdomen showed a tubular filling defect in the common bile duct extending in to the left hepatic duct. On endoscopic retrograde cholangiopancreatography (ERCP), the extraction was difficult because of left ductal stricture and a knot at the end of the worm. Such a worm conformation is rarely reported in the literature. In addition to presenting a challenge during removal it may act as a nidus for further infections and damage to the biliary tree particularly if the worm is dead or decaying. RPC is a disease with high morbidity and mortality. HBA is argued as an inciting event in significant number of cases. Recognition of such worm conformations emphasizes the need of meticulous ductal clearance at the time of ERCP, subsequent deworming and improved sanitation to protect such case from subsequent dreaded complications.

Disulfiram-induced Fulminant Hepatic Failure

Introduction: Disulfiram has been used as an adjunct therapy in treatment of chronic alcoholism. Disulfiram-induced liver injury can range from asymptomatic elevations in serum aminotransferases to symptomatic liver injury with jaundice, and, rarely, to fulminant hepatic failure and death. We present a rare case of disulfiram-induced fulminant hepatitis. Case Presentation: A 66-year-old male with history of hypertension, diabetes mellitus, and atrial fibrillation on Coumadin was admitted with acute liver failure. He had a history of heavy alcohol use, and decided to quit alcohol three weeks prior to admission. He was started on disulfiram, but did not tolerate the medication, and stopped it 10 days prior to current admission. He presented with hypoglycemia, and was found to have elevation of liver enzymes with total bilirubin of 13, AST of 2749, ALT of 3423, and alkaline phosphatase of 293. INR was greater than 10. Work-up was negative for acute viral hepatitis, Tylenol, and salicylate toxicity. Coagulopathy initially reversed with vitamin K, and was felt to be due to Coumadin toxicity. There was no evidence of encephalopathy on admission. However, INR continued to remain elevated even after discontinuing Coumadin. CT did not show cirrhosis, but showed evidence of portal hypertension. He was started on N-Acetylcysteine protocol for acute liver failure. Liver function tests (LFTs) continued to increase, with bilirubin peaking at 36 mg/dL. Liver biopsy was planned, but deferred, as the patient developed fulminant hepatitis. He was not a liver transplant candidate due to recent alcohol use. Encephalopathy and coagulopathy continued to worsen, and the family opted for hospice. Discussion: Disufiram has been used in treatment of chronic alcoholism since 1948. It inhibits acetaldehyde dehydrogenase enzyme leading to accumulation of acetaldehyde. This leads to flushing, tachycardia, nausea, vomiting, and confusion. Chronic therapy with disulfiram is associated with mild aminotransferase elevations, but elevations above three times the upper limit of normal (ULN) occur in up to 4% of patients. Liver injury usually occurs within 2-12 weeks of starting disulfiram, but latency period tends to be shorter in cases of re-exposure. The clinical presentation of disulfiram-induced hepatotoxicity resembles acute viral hepatitis. In severe injury, the fatality rate is at least 10%. Histologically, findings include focal hepatocellular necrosis, lobular disarray, and chronic inflammatory cell infiltrates with eosinophils. Conclusion: Disulfiram-induced hepatotoxicity is associated with high mortality, and should lead to immediate discontinuation of the drug. If stopped early, complete recovery is expected within 4-6 weeks.

Herpes Simplex Virus Hepatitis in Infants: Clinical Outcomes and Correlates of Disease Severity

To better characterize the clinical outcomes of infants with herpes simplex virus (HSV) infection and identify useful correlates of disease severity. Infants aged ≤6 months with HSV infection treated between 1999 and 2009 were identified. In patients with concurrent hepatitis, laboratory and clinical variables were examined to identify predictors of specific outcomes, including death or the need for liver transplantation and the need for intensive care. Of the 15 patients enrolled, 4 (27%) had fatal disease and 2 (13%) required liver transplantation. Infants who lacked skin lesions (P = .04), had a positive HSV polymerase chain reaction result (P = .01), had more severe thrombocytopenia (P = .001), or had other organ system dysfunction (P = .002) were more likely to require intensive care. A higher International Normalized Ratio value (P = .001) and peak total bilirubin level (P = .0002) were predictive of death or the need for liver transplantation. Peak direct bilirubin level was predictive of the need for intensive care and of death or the need for liver transplantation (P = .04 and .009, respectively). HSV hepatitis represents a broad spectrum of disease from mild aminotransferase elevation to fulminant liver failure and death. HSV DNA detected by polymerase chain reaction, a lack of skin lesions, and the degree of coagulopathy, thrombocytopenia, and cholestasis portend unfavorable outcomes.

American association for the study of liver diseases endpoints conference: Design and endpoints for clinical trials in primary biliary cirrhosis

American association for the study of liver diseases endpoints conference: Design and endpoints for clinical trials in primary biliary cirrhosis

Sevoflurane Hepatotoxicity: A Case Report of Sevoflurane Hepatic Necrosis and Review of the Literature

Sevoflurane, a halogenated anesthetic, is associated with mild aminotransferase elevations but does not tend to cause clinically significant hepatotoxicity. We report a rare case of severe hepatic necrosis following exposure to sevoflurane during surgery. A 37-year-old man presented with nausea,vomiting, abdominal pain, and jaundice on the third postoperative day after an abdominal wall mass resection. Laboratory tests showed markedly elevated aminotransferase levels, hyperbilirubinemia, and coagulopathy. His viral hepatitis and human immunodeficiency virus (HIV) serologies were negative for acute infection, and his Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serologies were suggestive of recent EBV infection and remote CMV infection. Antinuclear antibody and anti-smooth muscle antibody screens were negative. Ceruloplasmin and serum copper values were in the normal range. The histopathological findings included an acute centrilobular cholestatic hepatocellular injury compatible with the clinical history of acute drug-induced hepatotoxicity. The patient improved with conservative management. Unlike other halogenated anesthetics, proposed mechanisms of sevoflurane hepatotoxicity include production of compound A, increased cytosolic free Ca(2+), and activation of free radical metabolizing enzymes. The patient was likely susceptible to toxicity due to an underlying EBV infection and a probable history of exposure to halogenated anesthetics. Sevoflurane is generally considered to be relatively safe for subjects with mild liver dysfunction, in comparison with other halogenated anesthetics. However, this case suggests that sevoflurane can lead to severe life-threatening hepatic necrosis in at-risk individuals.

Factors Associated With Increased Serum Alanine Aminotransferase Levels During the French Guiana Dengue Epidemic of 2005-2006

Mild elevation of aminotransferases is a common feature of dengue virus infection, and severe acute liver injury has been described. The aim of this retrospective study was to assess relationships between antipyretic drugs and chronic alcohol use and the increase in serum alanine aminotransferase (ALAT) level in patients hospitalized with dengue fever during the 2005-2006 dengue epidemics in French Guiana. In the 162 included patients in this study (99 adults [62%] and 63 children [38%]), 2 analysis were performed comparing (1) 64 adults (65%) with an ALAT value greater than twice the upper limit of the normal value and 35 controls (35%) and (2) 24 children (39%) with an ALAT value greater than twice the upper limit of the normal value and 38 controls (61%). The factors associated with ALAT elevation were: (1) acetaminophen exposure and length of intake in adults and (2) acetaminophen overdose during the hospitalization of children. Another analysis suggested a role for alcohol consumption. Acetaminophen and alcohol consumption should be searched and taken into account in dengue fever.

Efficacy and safety of azathioprine maintenance therapy in a group of Crohn's disease patients in China

To evaluate the efficacy and the safety of long-term azathioprine maintenance therapy in a group of Chinese patients with Crohn's disease. The efficacy of azathioprine (2.0 mg/kg/day) in controlling the disease relapse in 13 patients with Crohn's disease following clinical remission by prednisone or surgery were investigated. The Crohn's disease activity index (CDAI) and the Harvey-Bradshaw index, the reduction of steroid dosage and side-effects for an average of 18 months follow up were analyzed. Azathioprine was effective in controlling the disease relapse in 10 (by CDAI scores) or 11 (by Harvey -Bradshaw index) of 13 patients (76.9% and 84.6%, respectively) for at least 6 months. Azathioprine was not discontinued in a patient who experienced a temporary and mild elevation of aminotransferases 14 months after the initiation of therapy. However one patient who was co-administered with azathioprine and mesalamine (Pentasa) developed an episode of bone marrow suppression that ultimately required the withdrawal of both medications. Azathioprine is an effective agent which controls the relapse of Crohn's disease in most patients. Long-term remission can be achieved. Side-effects, including severe leukopenia, myelo-suppression and the mild elevation of hepatic enzymes, may occur in a small number of patients.