Severe Transaminase Elevation Research Articles

Starvation hepatitis and refeeding-induced hepatitis: mechanism, diagnosis, and treatment.

Anorexia nervosa (AN) is one of the most common psychiatric disorders among young adults and is associated with a substantial risk of death from suicide and medical complications. Transaminase elevations are common in patients with AN at the time of hospital admission and have been associated with longer lengths of hospital stay. Multiple types of hepatitis may occur in these patients, including two types that occur only in patients with AN: starvation hepatitis and refeeding-induced hepatitis. Starvation hepatitis is characterized by severe transaminase elevation in patients in the advanced phase of protein-energy deprivation and is associated with complications of severe starvation, such as hypoglycaemia, hypothermia, and hypotension. Refeeding-induced hepatitis is characterized by a milder increase in transaminases that occurs in the early refeeding phase and is associated with hypophosphatemia, hypokalemia, and hypomagnesaemia. Among the most common forms of hepatitis, drug-induced liver injury is particularly relevant in this patient cohort, given the frequent use and abuse of methamphetamines, laxatives, antidepressants, and antipsychotics. In this review, we provided an overview of the different forms of anorexic-associated hepatitis, a diagnostic approach that can help the clinician to correctly frame the problem, and indications on their management and treatment.

Choledocholithiasis Can Present with Marked Transaminases Elevation: Systematic Review and Meta-Analysis.

Extreme transaminase elevation > 1000 international units per liter (IU/L) is typically caused by hepatocellular injury due to ischemia, drugs, or viral infection. Acute choledocholithiasis can also present with marked transaminase elevation mimicking severe hepatocellular injury, contrary to the presumed cholestatic pattern. We searched PubMed/Medline, EMBASE, Cochrane Library, and Google Scholar for studies reporting the proportion of marked elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000IU/L in patients with common bile duct (CBD) stones. A proportion meta-analysis with a corresponding 95% confidence interval (CI) was used to pool the proportion of patients with extreme transaminase elevation. I2 was used to examine heterogeneity. We used CMA software utilizing a random effect model for statistical analysis. Three studies (n = 1328 patients) were included in our analysis. The reported frequency of ALT or AST > 1000IU/L in choledocholithiasis patients ranged between 6 and 9.6%, with pooled frequency of 7.8% (95% CI 5.5-10.8%, I2 61%). The frequency of patients with ALT or AST > 500IU/L was higher, ranging between 28 and 47%, with pooled frequency of 33.1% (95% CI 25.3-42%, I2 88%). This is the first meta-analysis to study prevalence of severe hepatocellular injury in patients with CBD stones. Results revealed that approximately one-third of patients with choledocholithiasis present with ALT or AST > 500IU/L. Furthermore, levels > 1000IU/L are not uncommon. An elaborate work-up for alternative etiologies of severe transaminase elevation is likely unwarranted in cases with clear evidence of choledocholithiasis.

Glycogenic Hepatopathy in a Teenage Girl with Diabetes Mellitus Type 1

Glycogenic hepatopathy (GH) refers to a relatively rare complication of diabetes mellitus (DM) type 1 which constitutes of reversible accumulation of excess hepatic glycogen, usually manifesting in the form of liver enzyme elevation along with hepatomegaly. The occurrence of the disorder is most commonly related to inadequate control of blood sugars. Herein, we report upon a case of an 18-year-old girl presenting with severe transaminase elevations owing to poor metabolic control, as well as the progression of her enzymes and general condition during and after her hospitalization.

Abemaciclib in combination with pembrolizumab for HR+, HER2− metastatic breast cancer: Phase 1b study

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9–11.1) and 26.3 months (95% CI: 20.0–31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2− MBC.

Comparative analysis of patients hospitalized for severe transaminase elevation according to etiology and laboratory findings

Amac: Transaminazlarda belirgin yukseklik saptanarak dahili kliniklere yatirilmis hastalarin etiyolojik, epidemiyolojik, klinik ve laboratuar bulgularinin degerlendirilerek akut hepatit tablosuna klinik ipuclari ile isik tutmak amaclanmistir. Gerec ve Yontem: Ocak 2010–Eylul 2013 yillari arasinda Ic Hastaliklari ile Enfeksiyon Hastaliklari Kliniklerinde yatirilan, transaminaz duzeylerinde ust sinirin en az bes kati yukseklik saptanan 102 hasta calismaya dahil edildi. Hastalarin yas, cinsiyet, etiyoloji, laboratuvar bulgulari, klinikte yatis sureleri ve karaciger enzim duzeylerinin normal duzeye donme sureleri retrospektif olarak incelendi. ANOVA, Kruskal-Wallis ve Ki-kare test niceliksel ve niteliksel verilerin analizinde kullanildi. Bulgular: Akut karaciger hasari olan 102 hastanin 58’i (%56,9) kadin, 44’u (%43,1) erkekti. Yas ortalamasi 46 yildi. Calismada 3 ana grubu toksik hepatit (%34,3), akut viral hepatit (%25,5) ve iskemik hepatit (%17,6) gruplari olusturdu. Bunu akut nonbiliyer pankreatit (%6,9), otoimmun hepatit (%4,9) ve diger (%10,8) gruplari izledi. Akut viral hepatitlilerde diger gruplara kiyasla transaminaz ve bilirubin degerleri anlamli (p<0,05) olarak daha yuksekti. Hastanede en uzun sure yatirilan hasta grubunu akut viral hepatitliler olusturdu. Karaciger enzimlerinin en gec duzeldigi grubu toksik hepatitliler olusturdu. Toksik hepatitlilerde en sik iki neden nonsteroid antiinflamatuvar ilaclar ve bitkisel urunlerdi. Iskemik hepatit grubunda, yas ortalamasi tum hepatit gruplarina gore anlamli olarak yuksek saptandi. Alkol kullaniminin, klinikte yatis suresi ve karaciger enzimlerinin normallesme suresi uzerinde etkili olmadigi goruldu. Sonuc: Transaminaz yuksekligi olan hastalarda hizlica etiyolojinin belirlenmesi, gereksiz yatis surelerinin kisaltilmasi ve laboratuvar testlerinin yerinde ve akilci kullanilmasi onemlidir. Calismamizin amaci akut karaciger hasarina klinisyen gozuyle dogru ve etkin bir yaklasim saglayabilmektir.

Acute Hepatitis Associated with “Thermogenic Fat Burner” Weight Loss Supplementation: A Case Report

Thermogenic fat burner treatments are used to increase an individual’s basal metabolic rate, thus mimicking exercise and inducing weight loss. In rare circumstances, these supplements are associated with hepatotoxicity. We describe the case of a 21-year-old male who presented with painless jaundice and a weight loss of 25% of body weight following 8 weeks of thermogenic fat burner supplementation. Laboratory investigations revealed a severe transaminase and bilirubin elevation (AST/ALT&gt;2000 IU/L, total bilirubin=148 μmol/L). An otherwise extensive workup, including a liver biopsy, did not identify a precise cause. Two weeks after discharge, his condition stabilized with a significant improvement in his laboratory abnormalities. In this report, we discuss the likely ingredients that contributed to the patient’s condition, including Garcinia cambogia and green tea leaf extract, and review similar cases documented in the literature.

Elevated Liver Enzymes: Emergency Department–Focused Management

BackgroundLiver function test (LFT) abnormalities are a common problem faced by emergency physicians. This has become more common with the introduction of laboratory panels and automated routine laboratory testing. Fortunately, not all patients with irregularities in liver enzymes possess underlying pathology. This emergency medicine focused review provides a discussion of the various biochemical tests, their underlying biological basis, and an algorithmic approach to the interpretation of abnormalities. ObjectiveOur aim was to provide emergency physicians with an overview of the evaluation and management of patients with elevated LFTs. DiscussionThe liver is a complex organ with multiple roles. The key biochemical markers of hepatic function can be organized into the groupings of hepatocellular, cholestatic, or functioning liver, based on underlying enzymatic roles. Pathologic alterations to these markers can be algorithmically assessed by separating disease processes of these groupings, followed by assessment of the magnitude of enzymatic elevation. This review conducts an in-depth evaluation of the differential diagnosis and emergency department–centered clinical response of elevated LFTs based on subcategories of mild, moderate, and severe transaminase elevation. ConclusionsBy understanding the biochemical basis of each LFT, it is possible to correlate laboratory findings to a patient's clinical presentation. An algorithmic approach can be taken to help narrow the spectrum of a differential diagnosis. This may assist providers in ensuring appropriate management and evaluation of the patient with elevated LFTs.

Transient liver function abnormality following treatment with rabbit antithymocyte globulin for nonmyeloablative hematopoetic stem cell transplant: Two case reports

Rabbit antithymocyte globulin (rATG) is increasingly used in nonmyeloablative hematopoetic stem cell transplant (HSCT). Elevated liver function tests (LFTs) have been reported for antithymocyte globulin in the treatment of aplastic anemia, but not when used in a conditioning regimen for HSCT. We describe two cases of patients receiving a conditioning regimen for HSCT containing rATG who developed a transient, severe transaminase elevation. In the first case, a 66-year-old woman with a history of acute myeloid leukemia received the first dose of rATG and the patient's transaminases were found to be extremely elevated within a few hours. The aspartate transaminase (AST) peaked at 1286 U/L and alanine transaminase (ALT) peaked at 991 U/L and both resolved within a week. In the second case, a 72-year-old woman with a history of non-Hodgkin lymphoma received the first dose of rATG and the AST and ALT were found to be 1212 U/L and 689 U/L, respectively, 1 h after finishing the infusion. Like the previous case, the transaminase elevation resolved within a week. LFT abnormalities induced by rATG during conditioning therapy for HSCT may be transient and have a rapid onset after the first dose, but quickly subside without any complications or sequelae. It is important to follow the LFTs closely, as well as monitor for any signs and symptoms of acute liver failure.

Glycogen hepatopathy in a 13-year-old male with type 1 diabetes

Glycogenic hepatopathy (GH ) is a rare cause of serum transaminase elevations in type 1 diabetes mellitus. We describe a 13-year-old male with a history of poorly controlled type 1 diabetes mellitus who presented with hepatomegaly and severe transaminase flares. Liver histology confirmed GH. Treatment consists of improving glycemic control. Hepatomegaly due to excess glycogen storage in poorly controlled type 1 diabetics has been associated with younger patients with poor glycemic control, occurring about 2-4 weeks after starting insulin treatment, and resolving upon glucose stabilization. We conclude that glycogenic hepatopathy can cause hepatomegaly and significant transaminase elevations in individuals with type I diabetes mellitus, The recovery of severe transaminase elevations in this patient illustrates the more benign course of GH, which is a condition with a far better prognosis. Clinician awareness of GH should prevent diagnostic delay and will provide better insight into the prevalence of GH.

A phase II clinical trial of neoadjuvant trabectedin in patients with nonmetastatic advanced myxoid/round cell liposarcoma (MRCL)

10525 Background: Trabectedin (ET-743, Yondelis), a marine-derived alkaloid has demonstrated significant activity in the treatment of soft tissue sarcomas (STS) in phase III trials, and has recently received EMEA approval in this indication. A subtype that accounts for 10% of STS, MRCL, displays the fusion FUS-CHOP in 95% of all cases. Preliminary results of neoadjuvant trabectedin (T) in advanced MRCL show reduction in the radiological density of the tumor, clinical improvement, and a pathological complete response (pCR) in the resected tumor mass. A phase II study to further determine the response to T in the MRCL population is presented. Methods: In this multicenter Phase II trial, patients (pts) with locally advanced (stage III) or locally recurrent MRCL were treated for 3 - 6 cycles with T (1.5 mg/m2 q3wk) in the neoadjuvant setting. Main endpoints were: pCR rate, objective response rate by RECIST, and correlation of molecular parameters from tissue samples with clinical outcomes. Results: Twenty-five pts with locally advanced MRCL have been recruited, of whom 20 are evaluable. All had the translocation (t12q13, 16p11) which causes the chimeric FUS-CHOP. Median age was 53 (23–75) and male:female ratio was 1. Thirteen pts completed therapy and underwent curative surgery. Pathological assessment was performed in 10 pts: 2 achieved pCR, 1 as per central pathology review and 1 by local pathology assessment. In addition, 1 pt had a very good pathological response. Ten patients remain to be histologically evaluated. Response rate by RECIST from pts who completed therapy was: 6 partial responses (46%) and 7 disease stabilizations. Remarkably, pathological response does not entirely correlate with response by RECIST since the pts with pCR still had radiological disease but no malignant component was found in the excised tumor mass (only connective and reactive tissue). Two serious adverse reactions of severe rhabdomyolysis, and asthenia, nausea and transaminase elevation were reported. Most common toxicities were liver enzyme elevation, neutropenia and thrombocytopenia. Conclusions: These preliminary results in terms of objective and complete pathologic responses, strongly suggest that T may have a role in the neoadjuvant setting in pts with MRCL. [Table: see text]

Hepatic safety of tipranavir plus ritonavir (TPV/r)-based antiretroviral combinations: effect of hepatitis virus co-infection and pre-existing fibrosis

The aim of this study was to evaluate the incidence and risk factors of severe liver events among HIV-infected patients treated with drug combinations including tipranavir boosted with ritonavir (TPV/r). One hundred and fifty patients were selected because they started a regimen that included TPV/r (500/200 mg twice a day) and had clinical visits at least every 3 months. Patients who discontinued TPV/r before their first visit were included. Twelve (8%) individuals developed grade>or=3 transaminase elevation (G>or=3TE). Nine (6%) patients discontinued TPV/r due to liver events. Six (8.6%) of 70 hepatitis C virus (HCV) co-infected patients and 6 (7.5%) of 80 subjects without HCV co-infection developed G>or=3TE (P=1). Liver fibrosis was evaluable in 48 (63%) of 76 individuals with hepatitis B virus and/or HCV infection. Four (13%) of 30 subjects with moderate-to-severe fibrosis and none of 18 with mild fibrosis showed G>or=3TE (P=0.3). None of nine patients with cirrhosis showed G>or=3TE. Liver tolerability of TPV/r was generally good in a cohort of patients with a high proportion of HCV co-infection, including subjects with advanced fibrosis. The presence of HCV co-infection was not associated with an increased risk of severe transaminase elevations.

Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage.

Liver Enzyme Elevation in Hepatitis C Virus (HCV)–HIV-Coinfected Patients Prior to and after Initiating HAART: Role of HCV Genotypes

Transaminase elevation is frequently seen in hepatitis C virus (HCV)-HIV-coinfected patients receiving antiretroviral therapy (ART), representing an increase in the immune response against HCV and being one of the mechanisms proposed to be involved. There is a report claiming that HCV genotype 3 is an independent risk factor. Our objectives were to assess the incidence of liver toxicity in an HIV-HCV-coinfected population with relatively preserved cellular immunity, and the role of HCV genotypes in the elevation of liver enzymes, both at baseline and after initiating ART. All HIV(+) patients with positive anti-HCV serology and CD4(+) cell counts above 100/mm(3) who began triple ART were identified, and their HCV-RNA levels and HCV genotype were determined. Liver enzymes were determined at baseline and bimonthly during follow-up. Of anti-HCV patients 147 were included, 128 (87.1%) of whom had detectable plasma HCV-RNA. HCV-1 and HCV-4 genotypes were found to confer an increased probability of having at baseline transaminases within normal limits over the other genotypes. Severe transaminase elevations (grades 3 and 4) occurred in 5/124 patients (4.0%), all with high pre-HAART ALT and positive HCV-RNA levels. Multivariate analysis showed that patients with genotype HCV-3 had a 3.27 times higher risk of developing HAART-related transaminase elevations of any grade. In conclusion, subjects with the HCV-1 genotype more often had transaminases within normal limits at baseline. The incidence of severe transaminase elevation after initiating ART was very low (4%) in this HIV(+) population with relatively preserved cellular immunity. HCV genotype 3 was identified as a risk factor for the development of transaminase elevation of any grade.

Role of Hepatitis C Virus Genotype in the Development of Severe Transaminase Elevation After the Introduction of Antiretroviral Therapy

Role of Hepatitis C Virus Genotype in the Development of Severe Transaminase Elevation After the Introduction of Antiretroviral Therapy

Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy.

Treatment of HIV infection with highly antiretroviral therapy (HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known. Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold rise above abnormal baseline values. Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patients received protease inhibitors (PIs), 90 received nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse, HCV coinfection, and older age as independent risk factors. Predictor variables in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95% confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99; 95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p = 0.001). Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcohol abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chronic HCV infection should be considered.