Elevated Liver Enzymes Research Articles

Genetic, Clinical, and Biochemical Characterization ofa Large Cohort of Palestinian Patients With Fanconi-Bickel Syndrome.

This study aims to investigate the clinical, biochemical, and genetic characteristics of Fanconi-Bickel syndrome (FBS) in a cohort of 20 individuals from Palestine and to identify novel pathogenic variants. A retrospective analysis was conducted on medical records from Al-Makassed Hospital's pediatric department spanning 2015 to 2023. Individuals diagnosed with FBS via molecular genetic testing were included in the study. Among the 20 genetically confirmed FBS patients, hepatomegaly was prevalent in 95%, whereas 70% exhibited both developmental delay and hypophosphatemic rickets, and 68.4% experienced growth retardation. Hypertriglyceridemia (HTG) was universal. Elevated liver enzymes and alkaline phosphatase were common, along with hypophosphatemia (95%) and urinary abnormalities. Genetic analysis revealed five distinct SLC2A2 pathogenic variants, including three previously unreported variants: p.Gln23Arg (c.68A > G), p.Thr353Arg (c.1058_1059delinsGG), and an exon 7 deletion. This study presents the largest single-center cohort of FBS patients, expanding our understanding of the disorder's phenotypic and genotypic spectrum. Despite FBS generally carrying a favorable prognosis, timely diagnosis remains crucial to prevent severe complications.

Lactate dehydrogenase as a biochemical marker for prediction of maternal and perinatal outcomes in hypertensive disorders in pregnancy

Hypertensive disorder of pregnancy includes new onset hypertension in pregnancy that is gestational hypertension and already existing hypertension that is chronic hypertension and gestational hypertension sometimes worsened by preeclampsia. Preeclampsia can cause complications such as eclampsia, HELLP syndrome, renal failure, pulmonary edema, stroke, and left ventricular failure. We aim to assessthe predictive role ofLactate Dehydrogenase value in Hypertensive disorders in pregnancy.After obtaining the informed consent, pregnant patients who were visiting Tertiary care centre and who were more than 28 weeks period of gestation were enrolled. Patients from both antenatal OPD clinics and from those who were presenting in emergency were included in this study. Serum levels of LDH were tested. Patients were monitored till delivery and 6 weeks following childbirth.The Mean serum levels of lactate dehydrogenase (LDH) in eclamptic group was 1495.000±859.1230, 804.569±224.5519 in severely preeclamptic group and in mild preeclamptic group ,mean LDH levels were 520.062±110.3944. The difference between both the groups was statistically significant (p < 0.001).Women with serum LDH levels > 800 IU/L and LDH levels between 601-800 IU/L, experienced considerably greater complications in preeclamptic-eclamptic group as compared to those with serum LDH levels < 600 IU/L.Thepreeclamptic-eclamptic group of women had increased serum LDH levels. Greater LDH levels were linked to worse outcomes for mothers including placental abruption, hemolysis elevated liver enzymes low platelet count (HELLP syndrome), pulmonary edema and maternal death and they were also linked to fetal complications including intrauterine fetal death (IUFD), intrauterine growth restriction and neonatal intensive care unit (NICU) admission.

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in 26 BBS genes. It affects multiple organs, including the kidney and liver, with varying degrees regarding extent and time of first manifestation. Structural renal anomalies are an early feature and end-stage kidney disease (ESKD) cumulates to 25% in adulthood. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Patients with genetically proven BBS were recruited from the University Children's Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients' digital records or medical letters. High-resolution ultrasound (US) imaging was utilized, including attenuation imaging (ATI), shear wave elastography (SWE) and dispersion (SWD) of liver tissue. 49 BBS patients (24/49 male; 1.1-51.0years, mean 17.8years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48), and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) of whom 3 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49), suggesting hepatic fibrosis, and it correlated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI, reduced GFR, and higher BMI SDS. We detected kidney and liver abnormalities in a higher percentage of BBS patients than previously reported, indicating a high sensitivity and diagnostic yield of the evaluated high-end US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.

German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health.

QOL-29. PREVALENCE, MANAGEMENT, AND OUTCOMES OF PROCARBAZINE-ASSOCIATED HYPERSENSITIVITY REACTIONS IN PATIENTS RECEIVING PCV FOR LOW-GRADE GLIOMA

Abstract Procarbazine is an alkylating agent commonly used to treat low-grade gliomas as part of the PCV regimen. The use of procarbazine is frequently limited by the development of hypersensitivity reactions (HSRs), which often require dose reduction or cessation of procarbazine therapy prior to the completion of a planned treatment course. The prevalence, clinical characteristics, and potential predictors of these reactions are not well defined. We conducted a retrospective cohort study of patients with low-grade glioma who received PCV between January 2016 and January 2024 at a tertiary academic hospital. Data on patient demographics, tumor type, clinical characteristics, treatment course, and hypersensitivity reactions were collected and analyzed. 61 total patients were included. The overall prevalence of HSRs was 60.7% (95% CI: 48.4% - 72.9%). The median cycle during which HSRs occurred was cycle 3 (IQR: 2-4, Range: 1-5). All HSRs involved the development of rash, with 86.5% being pruritic and 21.6% involving the face. Treatments for HSRs included antihistamines (62.2%), topical corticosteroids (35.1%), and systemic corticosteroids (27.0%). Three patients with HSRs presented to the emergency department with concern for anaphylaxis, and one required treatment with epinephrine. Out of six patients rechallenged with procarbazine after experiencing HSRs, one patient redeveloped a diffuse, pruritic rash that resolved with systemic corticosteroids. A multiple logistic regression analysis was performed to assess the association between HSRs and gender, age at PCV C1D1, elevated liver enzymes, and concomitant anticonvulsant use, but no significant correlation was observed. In summary, our study provides a contemporary and comprehensive analysis of the prevalence and severity of HSRs to procarbazine in patients with low-grade glioma. The high rate of HSRs in this population, including a relatively high rate of suspected anaphylaxis, should be considered carefully by clinicians in choosing chemotherapy for low-grade glioma and warrants routine counseling and close monitoring.

Diagnostic dilemma: a collision of pancreatic neuroendocrine tumor G3 and adenocarcinoma with extensive fibrosis.

An 82-year-old man presented with intermittent abdominal pain and elevated liver enzymes. Blood tests showed normal levels of tumor markers (CEA, CA19-9, NSE). Contrast-enhanced computed tomography (CE-CT) revealed a 20mm hypovascular mass in the pancreatic head. Magnetic resonance imaging indicated low intensity on both T1- and T2-weighted images and high intensity on diffusion-weighted images. Endoscopic ultrasonography visualized an irregular hypoechoic mass. Initially, it was diagnosed as pancreatic ductal adenocarcinoma (PDAC) based on imaging. Subsequent histopathological analysis via endoscopic ultrasound-guided fine-needle aspiration revealed a neuroendocrine tumor (NET). The preoperative diagnosis was changed to a pancreatic NET grade1. Consequently, a pancreaticoduodenectomy was performed. Histopathological examination of the resected specimen unveiled a mixed tumor-NET-Grade1/Grade3 and invasive PDAC. No clear transition between the NETs and PDAC was observed. The high grade of NET with significant fibrosis contributed to decreased enhancement of CE-CT. Finally, we diagnosed this case as a pancreatic collision tumor involving both NET and PDAC components, with lymph node metastases attributed to the NET components. In this case, achieving an accurate preoperative diagnosis was challenging despite utilizing both imaging and biopsy diagnostics. This unique case underscores the difficulties encountered in the preoperative assessment of mixed tumors.

The effect of hereditary thrombophilia on recurrent pregnancy loss: a retrospective cohort study

ObjectiveThrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey.MethodsThis retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed.ResultsRPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0–3.0] vs. 4.0 [3.0–5.0]), parity (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), live birth (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), anembryonic pregnancy (0 [0–0] vs. 0 [0–0]), miscarriage (0 [0–1.0] vs. 3.0 [2.0–3.0]), and stillbirth (0 [0–0] vs. 0 [0–0]) numbers differed significantly between the groups (p < 0.05). While no significant differences were determined in MTHFR A1298C, Factor V Leiden, factor II prothrombin G20210A, or homocysteine levels (p > 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027) .ConclusionThe homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results.

HELLP Syndrome Developing at 14 Weeks of Gestation: An Extremely Rare Case Report and a Literature Review

Introduction: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a disease of pregnancy that occurs very rarely before 20 weeks of gestation. We report a case of HELLP syndrome developing at 14 weeks and 2 days of gestation. Case Presentation: A 33-year-old Asian primipara at 14 weeks and 2 days of gestation visited the emergency room with a fever and headache. Initial blood pressure was 140/70 mm Hg, temperature 38.5°C, heart rate 130 beats/min with tachycardia. Her prenatal examination has been unremarkable, and fetal ultrasonography was within normal range. The laboratory results showed low platelet count with elevated liver enzymes, D-dimer, and fibrinogen but no sign of jaundice. Her WBC differential suggested a bacterial infection. Thus, we diagnosed early HELLP syndrome and immediately started conservative treatments. One day after admission, symptoms and laboratory results showed aggravation of the disease. We performed termination, followed by dilation and curettage for retained placenta. Her general condition improved rapidly after the operation. Placental biopsy showed both acute and chronic inflammation. She also had anticardiolipin antibody IgM, and after discharge, she was referred to a rheumatology specialist to address the antiphospholipid syndrome issue. Discussion: Although the triggers of HELLP syndrome are unclear, a recent inflammatory hypothesis suggests that placenta-derived inflammatory cytokines are involved. In our case, the anti-cardiolipin antibody may have triggered microangiopathy of the placenta. Our analysis of published HELLP cases revealed that, apart from the three diagnostic criteria, the most common abnormal laboratory finding was antiphospholipid antibodies. Therefore, despite its rarity, if a sign of inflammation is present in a patient, it is important to consider HELLP syndrome regardless of gestational age

Rescue of a spontaneous subcapsular hepatic hematoma associated with HELLP syndrome: A case report.

Spontaneous subcapsular hepatic hematoma (SSHH) is a rare yet severe complication of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome that can lead to life-threatening situations for both the mother and fetus. Determining an appropriate therapeutic strategy remains challenging, as it involves choosing between surgery, microinvasive percutaneous transhepatic drainage, or conservative treatment alone. Further successful cases are needed to support the optimal option. We retrospectively collected a patient's clinical record and imaging data to elucidate the natural progression, response to noninvasive treatment, and outcome of SSHH associated with HELLP syndrome. A 34-year-old woman, who underwent a cesarean section due to suspected fetal distress, developed SSHH accompanied by the potential risk of rupture and deteriorated serology within the first 24 hours after delivery. Emergency blood routine examination, serum biochemistry analysis, and computed tomography of the abdomen revealed a SSHH associated with HELLP syndrome. The main rescue measures included the use of corticosteroids, antihypertensive drugs, and platelet transfusion. A positive effect on the patient's condition was exhibited within 24 to 48 hours. The majority of the subcapsular hepatic hematoma could be absorbed without any sequelae over a period of 7 months. For patients with pregnancy-induced hypertension, there is a heightened risk of HELLP syndrome occurrence in subsequent pregnancies. The assessment and treatment of SSHH should be conducted by an experienced multidisciplinary team. In addition to timely delivery, the administration of corticosteroids, usage of antihypertensive medication, and platelet transfusion are necessary, particularly within the first 48 hours if the patient's condition permits. This approach would provide valuable insights for further therapeutic decisions and facilitate a preliminary prognosis assessment.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

Persistently elevated liver enzymes and bile acids, icterus, and weight loss in a 1.5-year-old Thoroughbred colt.

Persistently elevated liver enzymes and bile acids, icterus, and weight loss in a 1.5-year-old Thoroughbred colt.

The Efficacy of Flaxseed Oil on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent liver disorder and a leading cause of elevated liver enzymes. Previous research indicates that a diet rich in polyunsaturated fatty acids (PUFAs) can alleviate liver insulin resistance. This study investigates the therapeutic effects of flaxseed oil, a primary PUFA source, on NAFLD treatment. In a randomized clinical trial comprising 60 NAFLD patients diagnosed with NAFLD of grades 1, 2, and 3, participants were assigned to either a flaxseed oil capsule group or a placebo group for 2 months. Before the intervention, both groups showed no significant differences in examined parameters. However, after the intervention, the flaxseed oil group exhibited significant improvements in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), fasting blood sugar (FBS), and total bilirubin compared to the placebo group. Specifically, reductions were observed in AST (p=0.010), ALT (p=0.047), ALP (p<0.001), FBS (p=0.016), and total bilirubin (p=0.004). These findings suggest that flaxseed oil may hold promise as a therapeutic intervention for NAFLD, highlighting its potential in managing liver disease and metabolic parameters.

Acute Hepatitis Related to Hepatitis E Virus Genotype 3f Infection in Brazil.

The hepatitis E virus (HEV) is an important causative agent of acute hepatitis (AH). Despite reports of human infection in Brazil, the investigation is not routinely conducted, even in cases of elevated liver enzymes. This study evaluated two groups: group 1-patients with acute hepatitis A (n = 44); group 2-patients with nonA-C AH (n = 47). They were tested by enzyme immunoassay for anti-HEV IgM/IgG and real-time PCR for HEV RNA detection. The positive sample for HEV RNA was submitted for sequencing. The seroprevalence of anti-HEV IgM and IgG in group 1 was 4% (2/44) and 14.5% (7/44), respectively. Viral RNA was not detected in any sample. In group 2, the anti-HEV IgM positivity was 4.3% (2/47), and IgG 14.9% (7/47). RNA was detectable in one case, which presented a viral load of 222.4 IU/μL and positive anti-HEV IgM/IgG. In the phylogenetic analysis, the genotype identified was HEV-3f. These results indicate that HEV infection should be considered a possible diagnosis in cases of non-A-C AH. The patient identified with acute hepatitis E had recently traveled to the Northeast region of Brazil (Garanhuns city in Pernambuco state), where there are reports of high HEV seroprevalence among pigs. The close phylogenetic relationship observed between the sequence characterized in this study and strains isolated from pigs in nearby cities where the patient went suggested a possible zoonotic transmission in this region. This study highlights the importance of expanding studies and improving surveillance to understand better and manage HEV infections nationwide.

Phenytoin-induced DRESS syndrome: A multidisciplinary case study in precision medicine and advanced therapeutics

This case report aims to examine the diagnostic and therapeutic approach for phenytoin-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome in a pediatric patient, emphasizing the importance of early recognition and intervention. A 17-year-old male presented with a pruritic rash, fever, lymphadenopathy, and elevated liver enzymes one month after starting phenytoin for epilepsy. Diagnosis was confirmed using the RegiSCAR scoring system, which objectively assessed clinical and laboratory findings. The patient received high-dose corticosteroids and N-acetylcysteine (NAC) after discontinuing phenytoin, with regular monitoring of clinical and laboratory parameters. Timely withdrawal of phenytoin, along with corticosteroid and NAC therapy, led to the resolution of symptoms without long-term complications. The RegiSCAR scoring system proved invaluable for accurate and swift diagnosis, supporting its utility in pediatric DRESS cases. This case also suggests the potential of genetic screening, particularly HLA typing, for identifying high-risk individuals, although it was not utilized here. Early diagnosis and multidisciplinary management are critical for favorable outcomes in pediatric DRESS cases. Routine HLA screening could help prevent DRESS syndrome in patients prescribed high-risk medications, though further studies are needed to assess feasibility and cost-effectiveness. This case underlines the value of standardized treatment protocols and personalized medicine in managing drug hypersensitivity reactions effectively.

Prevalence, Risk Factors, and Clinical Profiles of Hepatitis D Virus in Nigeria: A Systematic Review, 2009–2024

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection.

Impact of phosphatidylethanol in the surveillance for alcohol use in post-liver transplant population: A retrospective study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation in the United States. The aim of this study was to describe the impact of phosphatidylethanol (PEth) in the surveillance for alcohol use after liver transplantation. We conducted a single-center retrospective study to assess the impact of phosphatidylethanol (PEth) for the surveillance of alcohol use and its correlation to health outcomes. We compared orthotopic liver transplant (OLT) recipients for ALD transplanted between 2016 and 2018, before the introduction of PEth, to those transplanted between 2019 and 2022, after the introduction of PEth. Alcohol relapse versus nonrelapse cohorts were also compared. Follow-up time for all cohorts was limited to 3 years post-OLT. Continuous variables were analyzed with an independent t-test and categorical variables with Fischer's exact test and chi-square test. The Kaplan-Meier method and log-rank test were used to assess alcohol-free survival. We reviewed 263 patients who were transplanted for ALD; 46 (17.5%) patients were noted to have at least one episode of alcohol relapse after their transplant. Patients with alcohol relapse had more frequent episodes of elevated liver enzymes compared with nonrelapsed patients (4.35 episodes vs. 2.46 episodes respectively, p < 0.001). The number of hospitalizations was also noted to be elevated among relapsed versus nonrelapsed patients; however, this was not statistically significant (2.85 vs. 2.50 respectively, p = 0.307). When comparing relapse rates before and after the introduction of PEth, relapses were notably detected more frequently after the introduction of PEth (17% vs. 7%, p = 0.012). No difference was noted in rates of mortality between patients who did or did not relapse. Overall, PEth is an effective surveillance tool in the postliver transplant population to monitor for alcohol relapse. Early detection of relapse can lead to opportunities for early intervention to avoid alcohol-related complications.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Predictors of abemaciclib discontinuation in patients with breast cancer: a multicenter retrospective cohort study

ObjectiveThis study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer.Material and MethodsBetween November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to discontinuation for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis.ResultsBaseline weight < 54 kg, bone metastases, and hemoglobin level ≤ 12.4 g/dL were independent predictors of abemaciclib discontinuation for any reason. The main adverse events leading to abemaciclib discontinuation were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight < 54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea.ConclusionPatients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment discontinuation. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.

Liver safety of tolvaptan in patients with autosomal dominant polycystic kidney disease: interim data from a post-authorization safety study.

After the risk of drug-induced liver injury was detected during tolvaptan clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), a post-marketing pharmacovigilance study was required for European Union regulatory approval. This is an interim analysis from a prospective, observational study enrolling patients prescribed tolvaptan for ADPKD in routine clinical practice. Data were obtained through physician records collected during regular care. Per the prescribing label, liver transaminases were to be monitored monthly for the first 18months of treatment and once every 3months thereafter. Patients and physicians were required to report adverse events suggestive of serious and potentially fatal liver injury. Data collection was from October 2016 to April 2022. Of 2074 patients (median follow-up 528days), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 times the upper limit of normal (ULN) were reported in 75 (3.6%) patients. At data cut-off, the enzyme elevations were confirmed for 65 patients. Among the 65 confirmed patients, in addition to transaminase elevations, there were 69 adverse events suggestive of liver injury. Tolvaptan was interrupted or withdrawn in 59/65 (90.8%) participants with confirmed ALT or AST ≥3times the ULN, with most transaminase elevations and adverse events resolved or resolving at data cut-off. No liver enzyme elevations met laboratory criteria for Hy's law cases. Transaminase elevations occurred post-marketing in a similar proportion of patients as reported in clinical trials (4.4-5.6%). Regular monitoring per label facilitates prompt detection of liver adverse events and intervention to mitigate the risk of severe injury.