Elevated Liver Enzymes Research Articles

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

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.

Impact of SGLT2 inhibitors on liver-related outcomes in patients with heart failure - a population-based study in HK

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now recommended for heart failure with preserved ejection fraction (HFpEf). While their side effects on respiratory and renal outcomes in patients with type 2 diabetes have been studied, the impact on liver-related diseases within HF patients is not well-established. Purpose This study aims to evaluate the association between SGLT2 inhibitor use and the risks of adverse liver events among HF patients. Methods We conducted a retrospective cohort study using the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify 80,248 HF patients (mean age 73.37 ± 12.88 years; 49.2% male) between 2013 and 2022. Propensity score matching was applied to achieve a 1:3 ratio of SGLT2 users to non-users, ensuring balanced baseline characteristics. Competing risk regression within Cox proportional hazards frameworks quantified the risks for cirrhosis, hepatocellular carcinoma, liver-related death, and significant elevations in liver enzymes (ALT or AST >3x normal and bilirubin >2x normal). Results During a median follow-up of 6.02 years (interquartile range: 3.48–9.25 years), there were 12,103 liver-related deaths. SGLT2 was associated with a 52% reduced risk of cirrhosis (adjusted subdistribution hazard ratio [SHR]: 0.48; 95% confidence interval [CI]: 0.36-0.65), a 61% lower risk of hepatocellular carcinoma (SHR: 0.39; 95% CI: 0.26-0.42), a 13% decreased risk of liver-related death (SHR: 0.87; 95% CI: 0.77-0.98), and a 19% risk reduction in elevated liver enzymes (SHR: 0.81; 95% CI: 0.68-0.96). 5-year cumulative incidences were 1.7%, 0.62%, 13%, and 5.4%, respectively, for SGLT2 users compared to 3.7%, 1.9%, 16%, and 7.0% for SGLT2 nonusers. Conclusion SGLT2 use is associated with a decreased risk of adverse liver outcomes in HF patients. This suggests a potential protective role for SGLT2 in liver health within this population.

Serum circulating liver enzymes and human diseases

Abstract Background This study aimed to comprehensively investigate the observational and Mendelian randomization (MR) associations between liver enzymes (ALP, ALT, AST and GGT) with a wide spectrum of human diseases. Methods UK Biobank data was used for observational analysis. Cox proportional hazard models were used to quantify the observational associations between liver enzymes and risks of 1109 diseases, adjusted for covariates. A correction was applied to allow for multiple comparisons. Two-sample MR was performed to replicate the identified observational associations. We assessed the strength, consistency and pleiotropy of these MR associations. Results In 438571 participants with a median 12.4 years of follow-up, we found evidence linking liver enzymes and 654 diseases, 254 of which were further assessed in subsequent MR. In MR, 52 associations were replicated (10 for ALP, 14 for ALT, 10 for AST and 18 for GGT). Specifically, ALT was associated with liver conditions, diabetes, abnormal bleeding from the female genital tract, and prostate cancer. AST showed associations with prostate cancer, anxiety, diabetic neuropathy, and stroke. GGT was linked to hepatic and biliary conditions, coronary atherosclerosis, and pneumonia, while ALP displayed positive associations with vitamin D-calcium-parathyroid-bone conditions. Conclusions Elevated liver enzymes are risk factors for a wide range of hepatic and extrahepatic diseases, predominantly digestive, circulatory, metabolic/endocrine (including diabetes) diseases. Furthermore, the four liver enzymes demonstrated distinct patterns of disease associations. Key messages • Elevated liver enzymes are risk factors for a wide range of hepatic and extrahepatic diseases. • The four liver enzymes demonstrated distinct patterns of disease associations.

Safety and Tolerability of Nintedanib in Patients with Fibrosing Interstitial Lung Diseases: Post-marketing Data.

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis-associated interstitial lung disease (ILD). We present global post-marketing safety data for nintedanib in these fibrosing ILDs. Data on adverse events in patients with fibrosing ILDs who were treated with nintedanib were collected via spontaneous reporting and solicited reporting in various studies (excluding clinical trials).Data were collected from 15 October 2014 (first regulatory approval) to 15 October 2023. Adverse events were coded using the Medical Dictionary for Regulatory Activities. Cumulative exposure to nintedanib was estimated using sales data. Cumulative exposure to nintedanib was 380,557 patient-years. Diarrhoea was reported at a rate of 227.5 per 1000 patient-years. Only 2.6% of diarrhoea events were reported as serious. Of 39,788 (33.6%) diarrhoea events with a known time to onset, almost 60% occurred within the first 3months of treatment. The rate of serious liver enzyme and bilirubin elevations (including drug-induced liver injury) was 4.0 per 1000 patient-years. Bleeding was reported at a rate of 24.2 per 1000 patient-years. Most (81.3%) bleeding events were non-serious. The rates of myocardial infarction, ischaemic stroke, and venous thromboembolism were 3.3, 3.3, and 2.0 per 1000 patient-years, respectively. Gastrointestinal perforation was reported at a rate of 0.9 per 1000 patient-years. Post-marketing safety data on established and potential adverse events associated with nintedanib in patients with fibrosing ILDs, collected over 9years, demonstrated a safety profile that was similar to that established in clinical trials and provided in the product labels. Education of patients about the adverse events that may be associated with nintedanib, and the effective management of adverse events when they occur, is important to minimise the impact of adverse events and help patients remain on treatment.

Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma

Aggressive thyroid carcinoma, including radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC), are associated with significant morbidity and mortality and have limited therapeutic options. Distinct immune profiles have been identified in thyroid cancer subtypes suggesting they may be susceptible to immune checkpoint inhibition. To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma. This phase 2 nonrandomized clinical trial enrolled patients with RAIR DTC in a single center from October 2017 to May 2019, with exploratory cohorts in MTC and ATC. The data were analyzed between June 2021 and September 2023. Intravenous nivolumab, 3 mg/kg, every 2 weeks and ipilimumab, 1 mg/kg, every 6 weeks until disease progression, intolerable adverse events, or a maximum duration of 2 years. The primary end point of the study was objective response rate (ORR) in RAIR DTC, which was scored according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1. Key secondary end points included safety, progression-free survival, overall survival, and biomarker analyses. A total of 51 patients were registered, and 49 patients were evaluable for analysis. The median (range) age was 65 years (30-88 years), and 25 participants (51%) were female. ORR in the DTC cohort was 9.4% (3/32 [95% CI, 2.8%-28.5%]), with all partial responses in either oncocytic carcinoma (2/6 [33.0%]) or poorly differentiated thyroid carcinoma (1/5 [20.0%]). Clinical benefit rates were 62.5% (20/32) in the overall DTC cohort, including 83.3% (5/6) in oncocytic carcinoma and 40% (2/5) in poorly differentiated thyroid carcinoma. ORR in the exploratory ATC cohort was 30.0% (3/10 [95% CI, 6.7%-65.2%]), with a clinical benefit rates of 50.0% (5/10). No responses were observed in the exploratory MTC cohort. The safety profile was similar to prior reports with dual immune checkpoint inhibition (pruritus, rash, diarrhea, fatigue, and elevation of lipase and liver enzymes). The presence of NRAS tumor genetic sequence variations, but not BRAF V600E, was associated with worse outcomes. This phase 2 nonrandomized clinical trial reported clinical activity of dual immune checkpoint inhibition in aggressive thyroid cancer. The study did not meet its end point in the primary population of RAIR DTC and does not support further investigation in non-biomarker-selected DTC. However, the signal observed in ATC may merit further evaluation. ClinicalTrials.gov Identifier: NCT03246958.

Effects of Formaldehyde-Treated Feed on Rumen Metabolism and Blood Biochemistry in Lambs: A Review

This review evaluates the impact of formaldehyde treatment on feed for lambs, focusing on its effects on rumen metabolism and blood biochemical indicators. Formaldehyde is commonly used as a feed additive to improve nutritional efficiency and preserve feed quality. This review synthesizes data from various studies to assess how formaldehyde-treated feed influences rumen fermentation parameters, including volatile fatty acid (VFA) production, rumen pH, and microbial activity. Additionally, the review examines the effects of formaldehyde treatment on key blood biochemical markers such as glucose, urea nitrogen, and liver enzymes. Studies indicate that formaldehyde treatment can enhance the stability and digestibility of feed, potentially improving nutrient utilization and overall animal performance. The preservation of protein and reduction in feed spoilage are highlighted as significant benefits, contributing to more consistent rumen function and metabolic efficiency. However, the impact on rumen microbial populations and VFA profiles shows mixed results, with some studies reporting improved microbial efficiency and others noting minimal changes. The review also discusses potential adverse effects, including alterations in blood biochemical parameters. While formaldehyde treatment generally maintains or improves key indicators like blood glucose and protein levels, excessive use may lead to concerns such as elevated urea nitrogen levels and potential liver enzyme disruptions, the review concludes that formaldehyde-treated feed can be a valuable tool in optimizing feed efficiency and lamb health, provided it is used judiciously. Future research is recommended to further elucidate the long-term effects on rumen microbiota and metabolic processes, ensuring balanced benefits without compromising animal welfare.

Locally Advanced Splenic Flexure Tumor With Invasion And Formation Of Splenic Abscess

Introduction: Splenic abscesses are rare, with an incidence of 0.14-0.70% in autopsies, affecting mainly men and immunosuppressed patients. Symptoms include fever, abdominal pain, nausea, and vomiting. Splenic invasion by colon cancer at the splenic flexure is uncommon. We report a case of cancer at the splenic flexure resulting in a splenocolic fistula and splenic abscess. Case Description: A 43-year-old man, with a history of injectable drug use, presented with diffuse abdominal pain. Tests revealed leukocytosis, thrombocytopenia, and elevated bilirubins and liver enzymes. A CT scan identified thickening in the colon and a splenic abscess. Total splenectomy and left colectomy with colon-colonic anastomosis were performed. Discussion: Splenic abscesses are rare and, when associated with colonic neoplasms, present a diagnostic and therapeutic challenge. This case highlights the importance of aggressive surgical intervention to treat tumor invasions and associated complications.

Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment

ObjectiveTo report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled data from three randomised clinical trials (RCT)...

The Strategic Management of Infected Pancreatic Pseudocyst in the Postpartum Period After Cesarean Delivery in a Pregnancy Complicated by Preeclampsia/Hemolysis, Elevated Liver Enzymes, and Low Platelets (HELLP) Syndrome and Shock

The Strategic Management of Infected Pancreatic Pseudocyst in the Postpartum Period After Cesarean Delivery in a Pregnancy Complicated by Preeclampsia/Hemolysis, Elevated Liver Enzymes, and Low Platelets (HELLP) Syndrome and Shock

Exploring the Neuroprotective Behaviour and Hepatoprotective Effects of Plumbagin in MPTP-Induced Parkinson's Disease

Aims: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms like tremors and bradykinesia, as well as non-motor symptoms such as sleep disturbances and autonomic dysfunction. Recent research suggests a link between PD and liver dysfunction, including altered metabolism and elevated liver enzymes. Plumbagin, recognized for its antioxidant and neuroprotective properties, may offer therapeutic benefits. This study explores its effects on both motor and non-motor symptoms in MPTP-treated mice, as well as its impact on liver function through serum enzyme analysis. The aim is to assess the neuroprotective and hepatoprotective potential of plumbagin in countering MPTP-induced neurodegeneration and liver dysfunction. Methodology: Thirty mice (22-30g, 8-12 weeks old) were randomly assigned to five groups of six each. The experiment spanned 28 days, with the mice housed under controlled conditions and provided standard feed and water. Behavioral tests, including the Marble Burying and Tail Suspension tests, were conducted to assess anxiety and depressive-like behavior. Serum biochemistry, including ALT, AST, and BUN, was measured using standard ERBA kits to evaluate liver function health. Results: In the marble burying and tail suspension tests, MPTP-induced mice (DC group) exhibited significantly higher anxiety and depressive-like behaviors compared to the sham and plumbagin groups. Plumbagin treatment (PD) and levodopa (LS) significantly reduced these behavioral symptoms. Liver function markers (ALT, AST, ALP) and BUN levels were elevated in DC mice, indicating liver and kidney damage, while plumbagin treatment mitigated these effects, showing values comparable to the standard treatment (LS). Conclusion: This study demonstrates that MPTP exposure affects both the central nervous system and liver function, leading to anxiety, depression, and liver damage, as evidenced by elevated liver enzymes. Plumbagin showed protective effects, reducing these behavioral and biochemical changes through its antioxidant properties, suggesting its potential as a therapeutic agent against MPTP-induced neurotoxicity and hepatotoxicity. These findings suggest that future research should investigate plumbagin's clinical potential for treating Parkinson's disease and liver dysfunction, offering promise for its use in developing neuroprotective therapies.

Intravenous paracetamol-related loss of consciousness at induction of anesthesia: A case report

Paracetamol (Acetaminophen) is an analgesics, antipyretic, and non-steroidal anti-inflammatory drugs. It is known to be one of the commonly used analgesics globally. Intravenous paracetamol has been frequently used in patients as analgesics and antipyretics. In therapeutic doses, paracetamol is well-tolerated and devoid of severe adverse reactions. However, significant adverse reactions associated with intravenous paracetamol may occur rarely. Nausea, vomiting, and constipation are known to be the common side effects of paracetamol. Other side effects include pain and reaction at the site of injection. The adverse reactions of paracetamol are as follows; hypotension, malaise, hypersensitivity reaction, elevation of liver enzymes, and thrombocytopenia. In our center, we found a case of intravenous paracetamol-related loss of consciousness at induction of anesthesia in a patient booked for myomectomy.

Chronic active Epstein–Barr Virus infection in a teenage girl with suspect autoimmune Hepatitis

BackgroundThe pathogenesis of chronic active Epstein–Barr virus (EBV) disease (CAEBV) is complex, involving infection, inflammation, and in some cases malignancy. EBV reactivates in some patients, who develop a chronic disease with infectious mononucleosis-like symptoms. On occasion, it might be confused with autoimmune hepatitis (AIH), based on the similar symptoms and elevated liver enzymes. We aimed to describe a similar case to remind reader of this disease.Case Presentation: A 14-year-old girl was diagnosed with AIH based on biopsy and biomarker findings 1 year prior to admission and initially presented with elevated liver enzymes, portal hypertension, and parenchymal liver disease. Despite steroid administration, her condition fluctuated, and she was admitted to the hospital several times. She underwent a renal biopsy because of massive ascites, hypoalbuminemia, and increased renal echogenicity. An evaluation for impaired liver function showed positivity for EBV IgM, IgG, and early antigen (EBEA) antibodies. A PCR-based assay showed 5265 copies/mL of EBV DNA in peripheral blood. Epstein–Barr encoding region (EBER) in situ hybridization revealed abundant positive cells. Immunohistochemistry for CD56 also showed abundant positive cells, and CAEBV was diagnosed on this basis. Chemotherapy, hematopoietic stem cell transplantation (HSCT), and liver transplantation were proposed but her family refused.ConclusionsCAEBV should be considered when diagnosing AIH or in cases of treatment-refractory AIH.

Management of high dose olanzapine poisoning in a young child under limited resource setting: a case report from Nepal

Introduction: Olanzapine, an atypical antipsychotic, is widely used for treating psychiatric conditions such as schizophrenia and bipolar disorder. Accidental overdose in children is rare but can lead to severe clinical effects. This case report discusses the management of a five-year-old male who accidently ingested 180 mg of olanzapine, the highest reported dose in a child under five years. Case Presentation: A five-year-old boy accidentally ingested 180 mg of Olanzapine, resulting in loss of consciousness and central nervous system depression. He exhibited hyperglycemia, elevated lactate, and prolonged prothrombin time, but no significant cardiovascular issues. Following intubation and supportive care, including intravenous medications and mechanical ventilation, the child gradually improved. He was discharged in stable condition with follow-up instructions. Discussion: Olanzapine toxicity in children presents with a variety of symptoms, including somnolence, hypotension, and neurological impairments, which are dose-dependent. Even in case of an exceptionally high overdose, the absence of cardiovascular toxicity supports safety profile of olanzapine. Common laboratory findings include hyperglycemia, elevated liver enzymes, and metabolic disturbances. Management involves airway protection, supportive care, and monitoring, as no specific antidote exists. Prompt and appropriate care, even in severe cases under limited resource settings, can lead to favorable outcomes. Conclusion: In cases of high dose accidental olanzapine poisoning in children, it is essential to begin quick intervention and comprehensive supportive care to achieve successful outcomes and can be managed even in limited resource settings. Preventive measures are crucial to avoid such incidents and careful monitoring is essential in managing pediatric olanzapine overdose.

Analysis and validation of clinical subgroups of Kawasaki disease in children in China: a retrospective study

ObjectiveAlthough Kawasaki disease (KD) is commonly regarded as a single disease entity, clinical subgroups have recently been described. We aimed to validate previous research on clinical subgroups and establish a...

Histologic Patterns of Ribociclib-induced Liver Injury

Abstract Introduction/Objective Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment. Methods/Case Report Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns. Results (if a Case Study enter NA) The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2). Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib. Conclusion Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.

Elevated Plasma Atherogenic and Triglyceride-Glucose Indices: Markers of Cardiovascular Risk in Transfusion-Dependent Thalassemia

Background Transfusion-dependent thalassemia (TDT) is an autosomal recessive disorder characterized by defective hemoglobin synthesis, leading to severe complications such as iron overload and multi-organ dysfunction. This study aims to elucidate the distinctive clinical and biochemical profiles of TDT patients compared to healthy controls, with an emphasis on cardiovascular risk assessment using novel markers such as the Plasma Atherogenic Index (PAI) and Triglyceride-Glucose (TyG) index. Methods This cross-sectional study included 32 TDT patients and 36 healthy controls, matched for age and gender. Comprehensive demographic, laboratory, and imaging data were collected and analyzed. TDT patients were further stratified based on cardiac involvement and ferritin levels. Key assessments included hemoglobin levels, liver enzymes, lipid profiles, and cardiac imaging. The PAI and TyG index were calculated to evaluate cardiovascular risks. Statistical analyses were performed using SPSS 27.0, employing Student’s t-test, Mann–Whitney U test, and Pearson chi-square test as appropriate. Results No significant differences in basic demographic parameters were observed between groups; however, TDT patients exhibited significant clinical and laboratory differences. Notably, these patients had lower hemoglobin levels, higher platelet counts, elevated liver enzymes (ALT and AST), and markedly increased ferritin levels. Lipid profiles were significantly altered, with lower levels of total cholesterol, HDL, and LDL but elevated triglycerides. Importantly, the PAI was significantly higher in TDT patients, suggesting an increased atherosclerotic risk. Subgroup analysis revealed that patients with cardiac involvement had worse metabolic profiles, higher TyG indices, and prolonged QT intervals, indicating heightened cardiovascular risk. As the iron burden increases, the TyG index and PAI may lose their sensitivity in distinguishing between varying levels of iron overload, suggesting that their effectiveness plateaus beyond a certain threshold of iron accumulation. Conclusion TDT patients show significant hematological and metabolic deviations, including elevated cardiovascular risk markers like PAI and TyG index. As iron burden increases, these markers lose discriminative power, and cardiac involvement escalates rapidly once a critical iron threshold is surpassed, as supported by studies showing a non-linear relationship between iron load and cardiac complications. Comprehensive cardiovascular risk assessment and tailored management are essential for these patients. Future studies should focus on tracking cardiovascular risk progression and the effects of targeted interventions.

A Case of Tick-borne Disease with Yezo Virus and Borrelia miyamotoi Coinfection.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

Liver and renal biochemical profiles of people with sickle cell disease in Africa: a systematic review and meta-analysis of case-control studies

BackgroundSickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa.MethodsThe protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords “liver function”, “renal function”, “sickle cell disease”, and “Africa” on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2.ResultsOverall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI − 2.99–20.23, I2 = 97.0%, p < 0.01), alanine transaminase (ALT) 7.82 (95% CI − 0.16–15.80, I2 = 99%, p < 0.01) and alkaline phosphatase (ALP) − 2.54 (95% CI − 64.72 – 59.64, I2 = 99%, p < 0.01) compared to controls. The pooled mean difference for the renal biochemical profiles creatinine − 3.15 (95% CI − 15.02; 8.72, I2=99%, p < 0.01) with a funnel plot asymmetry of t = 1.09, df = 9, p = 0.3048 and sample estimates bias of 6.0409. The pooled mean difference for serum urea was − 0.57 (95% CI − 3.49; 2.36, I2 = 99%, p < 0.01), and the estimated glomerular filtration (eGFR) rate was 19.79 (95% CI 10.89–28.68 mL/min/1.73 m2, I2 = 87%, p < 0.01) compared to controls.ConclusionPeople with SCD have slightly elevated liver enzymes and estimated glomerular filtration rates compared to controls in Africa. With all the heterogeneity (I2) > 50%, there was substantial variation in the reported articles’ results.Systematic review registrationPROSPERO CRD42022346771

Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic, oxidative stress, and inflammatory pathways.

Although single treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) or vitamin D3 (VD3) inhibited metabolic dysfunction-associated steatohepatitis (MASH) development in diabetic patients, their combination hasnot been explored previously. Hence, this study investigated the hepatoprotective effects of SGLT2i (empagliflozin) and/or VD3 against MASH in type 2 diabetic mice. Forty Mice were assigned into negative (NC) and positive (PC) controls, SGLT2i, VD3, and SGLT2i + VD3 groups. All animals, except the NC group, received high-fructose/high-fat diet (8 weeks) followed by diabetes induction. Diabetic mice then received another cycle of high-fructose/high-fat diet (4 weeks) followed by 8 weeks of treatment (five times/week) with SGLT2i (5.1 mg/kg/day) and/or VD3 (410 IU/Kg/day). The PC group demonstrated hyperglycaemia, dyslipidaemia, elevated liver enzymes, and increased non-alcoholic fatty liver disease activity score (NAS) with fibrosis. Hepatic glucose transporting molecule (SGLT2) with lipogenesis (SREBP-1/PPARγ), oxidative stress (MDA/H2O2), inflammation (IL1β/IL6/TNF-α), fibrosis (TGF-β1/α-SMA), and apoptosis (TUNEL/Caspase-3) markers alongside the PI3K/AKT/mTOR pathway increased in the PC group. Conversely, hepatic insulin-dependent glucose transporter (GLUT4), lipolytic (PPARα/INSIG1), antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL-10) molecules with the inhibitor of PI3K/AKT/mTOR pathway (PTEN) decreased in the PC group. Whilst SGLT2i monotherapy outperformed VD3, their combination showed the best attenuation of hyperglycaemia, dyslipidaemia, and fibrosis with the strongest modulation of hepatic glucose-transporting and lipid-regulatory molecules, PI3K/AKT/mTOR pathway, and markers of oxidative stress, inflammation, fibrosis, and apoptosis. This study is the first to reveal boosted hepatoprotection for SGLT2i and VD3 co-therapy against diabetes-induced MASH, possibly via enhanced metabolic control and modulation of hepatic PI3K/AKT/mTOR, anti-inflammatory, anti-oxidative, and anti-fibrotic pathways.