Transaminase Elevations In Patients 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.

Real-world experience of arbidol for Omicron variant of SARS-CoV-2.

At a crucial time with the rapid spread of Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus variant globally, we conducted a study to evaluate the efficacy and safety of arbidol tablets in the treatment of this variant. From Mar 26 to April 26, 2022, we conducted a prospective, open-labeled, controlled, and investigator-initiated trial involving adult patients with confirmed Omicron variant infection. Patients with asymptomatic or mild clinical status were stratified 1:2 to receive either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 5 days). The primary endpoint was the negative conversion rate within the first week. A total of 367 patients were enrolled in the study; 246 received arbidol tablet treatment, and 121 were in the control group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group [47.2% (116/246) vs. 35.5% (43/121); odds ratio (OR), 1.619; 95% confidence interval (CI): 1.034-2.535; P=0.035]. Compared to those in the SOC group, patients receiving arbidol tablets had a shorter negative conversion time [median 8.3 vs. 10.0 days; hazard ratio (HR), 0.645; 95% CI: 0.516-0.808; P<0.001], and a shorter duration of hospitalization (median 11.4 vs. 13.7 days; HR, 1.214; 95% CI: 0.966-1.526; P<0.001). Moreover, the addition of arbidol tablets led to better recovery of declined blood lymphocytes, CD3+, CD4+, and CD8+ cell counts. The most common adverse event (AE) was transaminase elevation in patients treated with arbidol tablets (3/246, 1.2%). No one withdrew from the study due to AEs or disease progression. As a whole, arbidol may represent an effective and safe treatment in asymptomatic-mild patients suffering from Omicron variant during the pandemic of coronavirus disease 2019 (COVID-19).

Risk Factors for Grade 3/4 Transaminase Elevation in Patients with Chronic Lymphocytic Leukemia Treated with Idelalisib

Introduction: Idelalisib (IDELA) is a selective PI3Kδ inhibitor approved for use with rituximab in patients with previously treated chronic lymphocytic leukemia (CLL). Reversible transaminase elevation (TAE) has been observed in all CLL clinical trials involving IDELA, with frequencies of Gr ≥3 elevation in company sponsored Ph 2 and 3 studies utilizing the approved dose of 150 mg orally twice a day, ranging broadly from approximately 10% (Sharman ASH 2014) to 41% (Hillmen EHA 2017). TAE leads to permanent discontinuation of IDELA in approximately 3% of patients (Coutre EHA 2015). Risk factors for Gr ≥3 TAE are not well understood. Lampson et al. (Blood 2016) reported a trend toward increased risk in younger patients and those with mutated IGHV in a series of 24 previously untreated CLL patients who received IDELA monotherapy. In the present study, we analyze the rates of Gr ≥3 TAE across all fully enrolled, Gilead sponsored Ph 2 and 3 studies with the goal of identifying risk factors related to patient and treatment characteristics and selected CLL genetic alterations. Methods: Data were reviewed from patients who received at least 1 dose of IDELA in any of 6 Ph 2 or 3 studies, 3 for treatment naive (TN) and 3 for relapsed/refractory (R/R) CLL. The following variables were used for analysis: age, prior therapy (Y vs N), combination with bendamustine plus rituximab (BR; Y vs N), del(17p) (Y vs N), and IGHV mutated vs unmutated. Results: A total of 853 patients were enrolled and treated with IDELA (Table 1) and comprise the safety analysis set (SAS). The median age was 67 y (range: 37-90), and the median IDELA exposure time was 11 mo (range: Conclusions: In this ad hoc analysis of 853 patients treated in Gilead sponsored trials of IDELA, younger age and TN status were risk factors for developing Gr ≥3 elevation of hepatic transaminases, as was treatment with BR for patients with R/R CLL. The highest incidence of Gr ≥3 TAE was observed in a single-arm trial of previously untreated patients with del(17p). IGHV mutation status was not a significant risk factor in this dataset. A statistical model of risk factors for Gr ≥3 TAE will be presented, considering interactions between the factors. Disclosures Brown: Infinity Pharmaceuticals: Consultancy; Pharmacyclics: Consultancy; Sun BioPharma: Consultancy, Research Funding; Astellas Pharma: Consultancy; Redx: Consultancy; Janssen: Consultancy; Celgene: Consultancy; AbbVie: Consultancy, Honoraria; Roche/Genentech: Consultancy; Janssen Oncology: Honoraria; Gilead: Consultancy, Research Funding; Pfizer: Consultancy; AstraZeneca: Consultancy. Zelenetz: Genentech Roche: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Mei Pharma: Research Funding; Hospira: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda Pharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria. Furman: TG Therapeutics: Consultancy; Verstem: Consultancy; Gilead Sciences: Consultancy; Abbvie: Consultancy, Honoraria; Sunesis: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; Genentech: Consultancy. Lamanna: Gilead: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Mato: DTRM: Research Funding; Pharmacyclics: Research Funding; Portola: Research Funding; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Gilead Sciences, Inc.: Membership on an entity9s Board of Directors or advisory committees; Kite: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy; TG Therapeutics: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Acerta: Research Funding; Regeneron: Research Funding; AbbVie: Consultancy, Research Funding. Montillo: Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Roche: Research Funding; Novartis: Honoraria; Genetech: Research Funding. O9Brien: CLL Global Research Foundation: Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy; Alexion: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; GSK: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Vaniam Group LLC: Consultancy; AbbVie: Consultancy; ProNAI: Other: Research Support: Honorarium, Research Funding; Celgene: Consultancy; Regeneron: Other: Research Support: Honorarium, Research Funding; Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; Sunesis: Consultancy; Astellas: Consultancy; Aptose Biosciences, Inc.: Consultancy. Dreiling: Gilead Sciences, Inc.: Employment. Dubowy: Gilead Sciences, Inc.: Employment, Equity Ownership. Kim: Gilead Sciences, Inc.: Employment. Munugalavada: Gilead Sciences, Inc.: Employment, Equity Ownership. Robak: Janssen: Consultancy, Honoraria, Research Funding; Akari Therapeutics Plc: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Hillmen: Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Roche: Consultancy, Honoraria, Research Funding.

Management of transaminase elevations in patients receiving idelalisib.

7532Background: Transaminase elevation associated with idelalisib (IDELA) typically occurs early during treatment (median onset, 8 wk) and is often asymptomatic. Currently recommended management of...

Incidence and predictive factors of transaminase elevation in patients consulting for dengue fever in Cayenne Hospital, French Guiana.

The objective of the study was to determine the incidence of transaminase elevation during dengue, and its predictive factors. In 2013, a longitudinal study was performed using data from all cases of dengue seen in Cayenne Hospital. Cox proportional modeling was used. Signs of major transaminase elevation were defined as an increase in aspartate amino transferase (AST) or alanine amino transferase (ALT) concentration over 10 times the normal value (10N). There were 1574 patients and 13 249 person-days of follow-up. The incidence rate for signs of transaminase elevation (10N) was 0.55 per 100 person-days. Six patients had major transaminase elevation with AST>1000 units (0.43 per 1000 patient-days), and 73 patients (4.6%) developed transaminase elevation with AST >10N. The variables independently associated with major transaminase elevation were hyponatremia, low platelets, dehydration, hematocrit increase, food intolerance, positive nonstructural protein 1 (NS1), age over 15 years and the notion of paracetamol intake. Although very frequent, the incidence of major transaminase elevation was lower than reported elsewhere perhaps because of good access to care, or of the particular serotype causing this epidemic. The patients with transaminase elevation tended to be older, more severe and taking paracetamol. .

Perfil de seguridad de rilpivirina: tolerabilidad general y neuropsiquiátrica, seguridad en pacientes coinfectados con virus de la hepatitis B/virus de la hepatitis C, y perfil lipídico

Currently available data on the safety and tolerability of rilpivirine come from the product information document, a phase IIb, dose-finding clinical trial (TMC278-C204), the phase III ECHO and THRIVE clinical trials, and the preliminary data from the STaR and SPIRIT clinical trials, with a total of 1,728 patients. The comparator has usually been efavirenz. All studies have found a lower incidence and severity of neuropsychiatric adverse effects, a better lipid profile, and a lower number of patients with subclinical transaminase elevation in patients treated with rilpivirine. However, because of the relatively low number of patients coinfected with hepatitis B or C virus, definitive conclusions cannot be drawn. Similarly, experience in patients with mild or moderate liver failure is limited and there are no safety data in patients with advanced liver failure.

Serum transaminase elevation in children with rotavirus gastroenteritis: Seven years’ experience

There are no studies on clinically significant transaminase elevation due to rotavirus gastroenteritis in the literature. Also, there are significant discrepancies among previous studies regarding the prevalence of increased serum transaminase levels in rotavirus infection. Patients investigated for rotavirus by stool antigen testing, who were followed between January 2005 and May 2012, were retrospectively enrolled in this study. Patients were divided into 2 groups according to their rotavirus results: rotavirus-positive acute gastroenteritis (RPAG) and rotavirus-negative acute gastroenteritis (RNAG) groups. A total of 4317 children who presented with acute gastroenteritis were assessed. The study was completed with 642 patients who met the inclusion criteria. In the RPAG group (n = 272), elevated alanine aminotransferase (ALT) was found in 42 (15.4%) patients and elevated aspartate aminotransferase (AST) in 69 (25.4%), while in the RNAG group (n = 370), these numbers were 25 (6.8%) and 44 (11.9%), respectively. The elevated ALT and AST levels were found to be significantly higher in the RPAG group than in the RNAG group (both p < 0.001). The prevalence of elevated transaminase levels was found to be similar with respect to gastroenteritis severity score (p > 0.05). The high serum transaminase levels normalized uneventfully in all patients in the RPAG and RNAG groups during follow-up. In this study, our results clearly signify a liver influence in rotavirus infections. Therefore, rotavirus infections should be kept in mind when evaluating the aetiology of transaminase elevation in patients with acute gastroenteritis.

Safety Profile of Maraviroc in Patients Coinfected With HIV-1 and Hepatitis B or C Included in the Maraviroc Expanded Access Program

Objective: To evaluate the safety of maraviroc with other antiretrovirals in patients with HIV-1 coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV).Methods: This was a multicenter, noncomparative, open-label, expanded access program (EAP) initiated in February 2007. Patients with CCR5-tropic HIV-1 and HIV-1 RNA ≥1000 copies/mL on their current treatment received maraviroc 300 mg (150 mg with protease inhibitors) twice daily with optimized background therapy (OBT), which could include the newer agents raltegravir, etravirine, and darunavir. The adverse event (AE) profile was compared with the active and placebo arms of the maraviroc phase III clinical trials MOTIVATE 1 and 2, where the OBT did not include these agents.Results: A total of 1,032 patients were enrolled: 51 HIV/HBV coinfected; 149 HIV/HCV coinfected, 9 HIV/HBV/HCV coinfected, and 823 HIV-1 monoinfected. Most (76%) received at least 1 newer agent. Overall AE frequency was comparable across coinfection groups (63%-72%). Hepatobiliary events were more common in HIV/HCV coinfection than in HIV monoinfection or HIV/HBV coin-fection (10.0, 4.8, and 3.1 per 100 patient-years, respectively). Across all coinfection groups, there was a trend toward lower exposure-adjusted rates of serious and hepatobiliary AEs in the EAP than in the MOTIVATE studies. Grade 3/4 transaminase elevations in patients receiving maraviroc in the EAP and MOTIVATE were comparable with those seen in the MOTIVATE placebo arm.Conclusion: Maraviroc plus an OBT did not increase the incidence of AEs or severe laboratory liver abnormalities in HIV-1–infected patients coinfected with HBV or HCV.

Liver toxicity of antiretroviral combinations including atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses: impact of pre-existing liver fibrosis

To appraise the rate of grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevation (TBE) in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C or hepatitis B virus (HCV or HBV, respectively) who receive atazanavir/ritonavir. Moreover, the relationship between these events and the degree of prior liver fibrosis was evaluated. A cohort of 189 HIV-infected patients, 175 co-infected with HCV, 4 with HBV and 10 with both, receiving atazanavir/ritonavir, was analysed. Baseline liver fibrosis was assessed in 113 (60%) patients. Twenty-four patients had cirrhosis, whereas such a diagnosis was ruled out in 58 patients. Twelve (6%) and 28 (15%) patients developed grade 3-4 TEs and grade 4 TBE, respectively. Eight (10%) of 84 patients with fibrosis >/=F2 versus 1 of 29 (3%) with F0-F1 (P = 0.51) developed grade 3-4 TEs. The frequencies of grade 3-4 TEs in patients with and without cirrhosis were 8% and 5% (P = 0.63), respectively. Grade 4 TBE was more common among patients with cirrhosis (35% versus 13%, P = 0.05) in the univariate analysis. In the multivariate study, the only predictor of grade 3-4 TEs was baseline CD4 cell count <300 cells/mm(3) [adjusted OR (AOR) (95% CI) = 8.77 (1.07-71.42), P = 0.04]. The factors independently associated with grade 4 TBE were baseline total bilirubin >1 mg/dL [AOR (95% CI) = 3.2 (1.21-8.45), P = 0.01] and age >40 years [AOR (95% CI) = 2.98 (1.19-7.47), P = 0.02]. Prior significant liver fibrosis or cirrhosis do not increase substantially the risk of severe TE associated with atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses.

Liver injury after beginning antiretroviral therapy in HIV/hepatitis C virus co-infected patients is not related to immune reconstitution

Transaminase elevations occur more frequently after beginning antiretroviral therapy in HIV-positive patients co-infected with hepatitis C virus (HCV). The mechanism of liver injury in these individuals is unknown, although immune reconstitution phenomena have been postulated. In 42 HIV/HCV co-infected individuals followed after beginning potent antiretroviral therapy, the development of liver injury was not associated with significant changes in serum HCV-RNA levels nor with greater CD4 cell increases. Underlying chronic hepatitis may thus increase the risk of liver toxicity by other mechanisms.

Retrospective Evaluation of the Effect of Valproate Therapy on Transaminase Elevations in Patients with Hepatitis C

To evaluate whether a relationship exists between valproate treatment and transaminase elevations in patients who are positive for hepatitis C virus (HCV). Retrospective medical record review. Veterans affairs medical center. A total of 214 HCV-positive patients; 28 were treated with valproate (study group), 186 were not (control group). Demographic characteristics; valproate treatment histories; plasma concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), albumin, and bilirubin; and exposure to other potentially hepatotoxic drugs, including probable alcohol abuse, were evaluated. Hepatotoxicity was staged by comparing maximum ALT and AST values against upper limits of normal or patients' mean elevated baseline ALT and AST values. Data were analyzed using a logistic regression model. Control patients and those with longer durations of HCV were more likely (p<0.0171 and p<0.0142, respectively) to exhibit higher stages of hepatotoxicity. More valproate-treated patients were exposed to other potential hepatotoxins at the time of peak transaminase elevations (50% vs 39%, p<0.005), whereas more control patients received two or more potential hepatotoxins (13% vs 4%, p<0.00005). Valproate treatment, either alone or in the presence of other potential hepatotoxins, does not appear to be related to increased transaminase elevations in patients with HCV

Transaminase Elevation in Patients Treated with Unfractionated Heparin or Low Molecular Weight Heparin for Venous Thromboembolism

The purpose of this study was to evaluate the in cidence of transaminase elevation in patients treated with un fractionated (UFH) or low molecular weight heparin (LMWH). Patients receiving UFH, nadroparin, or reviparin for venous thromboembolism and with normal baseline transaminase val ues were evaluated for serum transaminase levels 10-14 days after the start of heparin therapy or at the end of treatment. The incidence of high transaminase was 4.7% overall (95% CI, 2.2 to 7.3), while it was 2.9% (95% CI, 0.1 to 5.6) and 6.7% (95% CI, 2.5 to 11.0) with UFH and LMWH treated patients, respec tively. The difference was equal to -3.8% (95% CI, -8.9 to 1.2) and the common odds ratio was equal to 0.38 (95% CI, 0.12 to 1.16, p = .09). Nadroparin treated patients showed a 5.7% (95% CI, 1.3 to 10.2) incidence of high transaminase levels, while reviparin treated patients presented a 10.3% incidence (95% CI, -0.7 to 21.4). The comparison with UFH showed a mild trend in favor of UFH when compared with nadroparin, but not with reviparin. In conclusion, the incidence of trans aminase increase during heparin treatment for a venous throm boembolic event is equal to 3%, 6%, and 10% in UFH-, na droparin-, and reviparin-treated patients, respectively. LMWHs showed a slightly higher average incidences of hypertransami nasemia as compared with UFH. Differences did not reach statistical significance. Key Words: Unfractionated heparin— Low molecular weight heparin—Hypertransaminasemia.