Abnormal Liver Function Tests Research Articles

Evaluation of less treatment interruption of 6-Mercaptopurine by co-administration of ursodeoxycholic acid with chemotherapy in pediatric acute lymphoblastic leukemia

Background: Ursodeoxycholic acid, a bile acid, protects the liver through various mechanisms, including bile composition modulation and enhanced secretion. In ALL chemotherapy, 6MP is hepatotoxic, requiring dose reduction. UDCA is used to alleviate liver toxicity in ALL and other chronic cholestatic conditions. The study aims to evaluate the effectiveness of UDCA with chemotherapy in reducing 6MP treatment interruptions and its impact on treatment continuity in pediatric ALL. Methods: This randomized controlled trial study conducted at the Department of Pediatric Hematology and Oncology, BSMMU in pediatric ALL patients during chemotherapy from September 2018 to August 2019. Fifty children aged 1 to 18 years with ALL were enrolled, half receiving UDCA alongside chemotherapy and the rest forming the control group. Serum hepatic transaminases, total bilirubin, and CBC were monitored every 14 days. Statistical analysis was performed using SPSS, with significance set at p<0.05. Results: In this study of 50 pediatric ALL patients, there were no statistically significant age or gender differences between the "Case" (UDCA-treated) and "Control" groups. However, the UDCA group showed a significant decrease in abnormal liver function tests (32.0%) compared to controls (60.0%). Moreover, 6MP dose reduction was significantly lower in cases (4.0%) than controls (40.0%), indicating UDCA's potential hepatoprotective effects. Multivariate logistic regression revealed male gender and mean AST levels as significant factors associated with hepatotoxicity in pediatric ALL patients. Conclusions: Co-administration of UDCA with chemotherapy reduces hepatotoxicity in pediatric ALL patients on 6 MP, but more research is needed for dosage optimization and to assess impact on survival.

The Phenotypic Variability Associated with Hepatocyte Nuclear Factor 1B Genetic Defects Poses Challenges in Both Diagnosis and Therapy.

The evolving landscape of clinical genetics is becoming increasingly relevant in the field of nephrology. HNF1B-associated renal disease presents with a diverse array of renal and extrarenal manifestations, prominently featuring cystic kidney disease and diabetes mellitus. For the genetic analyses, whole exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were performed. Bioinformatics analysis was performed with Ingenuity Clinical Insights software (Qiagen). The patient's electronic record was utilized after receiving informed consent. In this report, we present seven cases of HNF1B-associated kidney disease, each featuring distinct genetic abnormalities and displaying diverse extrarenal manifestations. Over 12 years, the mean decline in eGFR averaged -2.22 ± 0.7 mL/min/1.73 m2. Diabetes mellitus was present in five patients, kidney dysplastic lesions in six patients, pancreatic dysplasia, hypomagnesemia and abnormal liver function tests in three patients each. This case series emphasizes the phenotypic variability and the fast decline in kidney function associated with HNF-1B-related disease. Additionally, it underscores that complex clinical presentations may have a retrospectively straightforward explanation through the use of diverse genetic analytical tools.

De Ritis Ratio to Predict Clinical Outcomes of Intermediate- and High-Risk Pulmonary Embolisms.

Background: Abnormal liver function tests can identify severe cardiopulmonary failure. The aspartate transaminase/alanine transaminase (AST/ALT) ratio, or the De Ritis ratio, is commonly used to evaluate acute liver damage. However, its prognostic value in pulmonary embolism (PE) is unknown. Methods: Two cohorts, including patients with intermediate- and high-risk PEs, were established: one with an abnormal baseline AST/ALT ratio (>1) and another with a normal baseline AST/ALT ratio (<1). The primary outcome was a 60-day mortality. Secondary outcomes included peak N-terminal pro-brain-natriuretic-peptide (NT-proBNP) levels, complications, and the need for critical care treatment. To assess the effect of abnormal AST/ALT ratios, inverse probability weighted (IPW) analyses were performed. Results: In total, 230 patients were included in the analysis, and 52 (23%) had an abnormal AST/ALT ratio. After the IPW correction, patients with an abnormal AST/ALT ratio had a significantly higher mortality rate and peak NT-proBNP levels. The relative risks of 60-day mortality, shock development, use of inotropes/vasopressors, mechanical ventilation, and extracorporeal life support were 9.2 (95% confidence interval: 3.3-25.3), 10.1 (4.3-24), 2.7 (1.4-5.2), 2.3 (1.4-3.7), and 5.7 (1.4-23.1), respectively. Conclusions: The baseline AST/ALT ratio can be a predictor of shock, multiorgan failure, and mortality in patients with a pulmonary embolism.

Living tape worms in the duodenal lumen: A rare case report

Fascioliasis is an infection caused by a trematode of the liver, Fasciola hepatica, which affects sheep, goats and cattle. Humans become accidental hosts through drinking contaminated water or ingesting raw green vegetables that has been contaminated with encysted metacercariae, which is the infective form. Fascioliasis has a hepatic phase and a biliary phase, each displaying different clinical signs and symptoms. Common signs and symptoms of the hepatic phase are abdominal pain, fever, eosinophilia, and abnormal liver function tests. The biliary phase of the disease usually presents with intermittent right upper quadrant pain with or without cholangitis or cholestasis. However, it is very rare to find a living flukes in the common bile duct (CBD) and duodenal lumen as it usually lives in gall-bladder and smaller biliary tracts. Here we report a case of human infestation of Fasciola hepatica, who presented with respiratory tract infection with abdominal pain &amp; dyspeptic symptoms and eventually during evaluation, an upper gastro-intestinal endoscopy revealed several flat worms at the second part of the duodenum. The worms were sent to microbiology department for identification. The organisms were confirmed to be Fasciola hepatica. The patient was given tablet Nitazoxanide 500mg 12 hourly for 7 days. The symptoms reduced in intensity after two days of nitazoxanide. The patient was then discharged with an advice of a stool routine examination after one month of completion of nitazoxanide. As fasciolosis is non endemic in our country, a high degree of suspicion is required to ensure early detection and management of such cases. Patients with abdominal pain, altered liver function tests &amp; eosinophilia should always be evaluated for a suspected Fasciola hepatica infection and should be kept as a differential in these cases. Bangladesh Crit Care J March 2024; 12 (1): 54-57

Dentification of some variable parameters in serum of COVID-19 patients in comparison with control group

The study intended to determine the correlation among coronavirus disease 2019 (COVID-19) infection and variable abnormalities in liver function test, lipids, and thyroid hormones. The study included 160 infected COVID-19 patients (80 females and 80 male) and 100 subjects as a control group (50 females and 50 males), attended the Al-Sader Medical City in Al-Najaf, Iraq during the period between January 2021 to October 2021. The patients' age ranged from 16-80 years old. Liver enzymes, lipid profile and thyroid hormone were tested. The results revealed a significant increase in liver function levels including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and Albumin (p&lt;0.05). Also, there was an increase in lipids levels including total cholesterol, low-density lipoprotein, and triglycerides. The result showed significant difference in levels of thyroid hormones triiodothyronine, thyroxine and thyroid stimulating hormone between COVID-19 infected patients and the control group. As well the antithyroid antibodies (thyroglobulin antibody, thyroid peroxidase antibody and thyrotropin receptor antibodies) were increased. There was a correlation between increasing thyroid hormones and their antibodies with infection by COVID-19. This study concluded that COVID-19 infection can induce disturbances in liver and thyroid function tests and changes in the lipid metabolism.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Comparing Feto-Maternal Outcomes in Pregnant Women With Normal and Abnormal Liver Function Tests: A Prospective Observational Study.

Pregnant women with abnormal liver function tests (LFTs)require proper evaluation and timely managementto reduce maternal and fetal morbidity and mortality. The present study was done with the objective of determining feto-maternal outcomes in antenatal women with abnormal LFTs and comparing them with antenatal women having normal liver function. The prevalence and possible causes of derangements in LFT were also identified. Pregnant women referred to an antenatal clinic for several reasons pertaining to abnormal liver functions, and those admitted to the labor room for delivery with abnormal LFTs were included in the study. The pregnant women with abnormal LFT were studied prospectively, and they were compared with pregnant women having normal LFT. The fetal and maternal outcomes were also noted. The pregnant women attending the antenatal clinic with a history of pruritus, abdominal pain, jaundice, nausea/vomiting, hypertension ascites, etc. and delivered at our facility were evaluated. One hundred and eight women had abnormal LFT defined by criteria laid down in material and methods. Eighty-seven women with normal LFT were taken for comparison. In the abnormal LFT, the main cause was intrahepatic cholestasis of pregnancy (IHCP). There were 6 (5.5%) maternal deaths in this group and none in the normal LFTs. There were 6 (5.6%) fetal deaths and 4 (4.6%) in the other group (p-value=1). The prevalence of abnormal LFT was 9.11% throughout pregnancy. Increased bilirubin and alkaline phosphatase (ALP) were significantly correlated with maternal mortality, while gestational age at birth, presence of meconium, appearance, pulse, grimace, activity, and respiration (APGAR) score, maternal mortality, and raised alkaline phosphatase level were found to be significantly associated with fetal mortality. Patients with abnormal LFT were significantly associated with maternal morbidity and mortality. However, fetal outcomes in patients with abnormal and normal LFT were similar. Hyperbilirubinemia and raised alanine aminotransferase (ALT) were significant predictors of maternal mortality.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Holmium Laser Lithotripsy in the Management of Difficult Biliary and Cystic Ductal Stones – A Case Series

Abstract Choledocholithiasis or common bile duct stone (CBDS) presents a unique challenge in the management of biliary stones. The clinical presentation of CBDS varies from asymptomatic CBDS, detected during the evaluation of gallstone disease to sinister presentation, like severe biliary pancreatitis. Asymptomatic liver function test abnormality, biliary colic, dilated common bile duct (CBD) on sonography for pain abdomen, and cholangitis are the part of the spectrum. Based on clinical suspicion and aided by laboratory parameters, the diagnosis is confirmed by modalities such as ultrasonography or magnetic resonance cholangiopancreatography or by endoscopic ultrasound. Endoscopic radiological cholangiopancreatography (ERCP) has evolved as a standard of care over the decades for the management of CBDS and surgical exploration of CBD is rarely resorted. ERCP is followed by laparoscopic cholecystectomy as a definitive treatment to prevent recurrence of CBDS. Multiple factors play a role in the successful extraction of CBDS. Two broad considerations are the size of stone and bilio-duodenal anatomy. Multiple studies have noted that stone size larger than 15 mm requires fragmentation for successful extraction. Mechanical lithotripsy has been cornerstone for the management of such cases. Besides size of stone, morphology and number of stones, narrow CBD (distal to stone), duodenal diverticulum and altered anatomy due to gastroduodenal surgeries pose a challenge in stone extraction and are collectively called difficult CBDS. Multiple modalities notably extracorporeal shortwave lithotripsy, holmium laser (Ho laser) lithotripsy, and electrohydraulic lithotripsy (EHL) have been studied for the fragmentation of large CBDS. Innovation in cholangioscopy and wider availability of peroral single-operator cholangioscope has brought EHL and Ho laser lithotripsy (LL) at forefront of management of difficult CBD stones. We share the experience of Ho LL for CBDS at a tertiary care hospital in Western India. The data of four patients, successfully managed with single-operator cholangioscopy (SoC)-guided Ho LL for indications ranging from large CBDS to residual large cystic duct stump stone has been discussed. These cases emphasize wider clinical application of SoC-guided Ho-LL beyond the size of the stone. Ho LL has revolutionized the management of difficult biliary stone. The major limitation is cost of care and availability of expertise.

Incidence of amoxycillin-clavulanic acid associated hepatotoxicity in an Australian children's hospital.

Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children. Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children's hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3 months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method. Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2 years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7 days and higher cumulative amoxycillin (>10 g) and clavulanic acid dose (>1 g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4 weeks (range 3-7). The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7 days, high cumulative amoxycillin (10 g) and clavulanic acid (>1 g) doses, those aged <2 years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7 days of treatment, particularly in those with other predisposing factors.

Liver injury in a non-obese patient: A case report

Non-Alcoholic Fatty Liver Disease (NAFLD) is a frequent cause of abnormal liver function tests and can be easily diagnosed in patients with obesity, hyperlipidemia, hypertension and diabetes mellitus. NAFLD is associated with insulin resistance and has always be treated as a part of metabolic syndrome. NAFLD used to be perceived as a seldom situation in non-obese subjects, but it’s currently becoming clear that NAFLD also occurs in this population. The main risk factors of non-obese NAFLD are still controversial and various in different regions, and can be contributed to insulin resistance as well. Herein, we report a liver injury in a non-obese patient with suspicious autoantibodies.

Elevated liver enzymes in a German tertiary-care hospital: Distribution, diagnostic steps and diagnosis groups.

The determination of liver blood tests is frequently performed in hospitalized patients, and abnormal values require further diagnostics. Yet, analyses considering the management of elevated liver enzymes are missing. Therefore, this study aimed to analyze the distribution of abnormal liver function tests and the subsequent diagnostic steps across different medical specialties. From our Hannover liver-injury database, we identified 63,300 cases of patients who were hospitalized between January 2008 and July 2021 with AST or ALT > 3 ULN or AP or TBI > 2 ULN at any time point during hospitalization. Of these, 29,547 cases fulfilled the inclusion criteria and were subjected to further analysis. Cases were analyzed according to the three groups: internal medicine, surgery and others. Analyses were performed regarding baseline characteristics, liver-related diagnostics and factors influencing hospital mortality. Elevated liver blood tests were mainly observed in internal medicine (n=17,762, 60.1%), followed by the surgery department 34.2% (n=10,105). Notably, 40.2% (n=11,896) developed liver enzyme elevation above the cut-offs during the hospital stay. Testing for hepatitis B and C was more often performed in the surgery department compared to in internal medicine. In total, 5.6% of the cases (n=1,640) had a liver biopsy. Hyperbilirubinemia (total bilirubine ≥ 2ULN) and AST/ALT ratios >2 were associated with in-hospital mortality. Clinicians are often faced with elevated liver enzymes. However, diagnostic steps differ between different specialties. Physicians should be aware of the increased in-hospital mortality in cases with hyperbilirubinemia or elevated AST/ALT ratios.

Hepatobiliary manifestations in patients with ulcerative colitis: a retrospective analysis.

Inflammatory bowel diseases (IBDs) are often associated with altered liver function tests (LFTs). There is little data on the relationship between abnormal LFT and IBD. Our study aimed to evaluate the prevalence and etiology of elevated LFT in patients with ulcerative colitis (UC) and to determine whether there is an association with clinical and demographic parameters. The clinical records of the Gastroenterology Outpatients Clinic at a single center were reviewed and screened for patients with UC from 2005 to 2014. In total, 263 patients were included. Patients with Crohn's disease (CD), colitis indeterminate, and colitis of other origins were excluded. Abnormal LFT and liver injuries were analyzed. A cohort of 182 patients was analyzed (114 males, 68 females; mean age = 50.2 ± 16.1 years). 58 patients had already been diagnosed with a hepatobiliary disorder. Patients with a known hepatobiliary disorder suffered from UC for a significantly longer duration. Elevated LFT in patients without known hepatobiliary disorders was 69.4%. Liver injury was found in 21.8%. A transient increase in abnormal LFT was shown in 59 patients (68.6%), a persistent increase was found in 27 patients (31.4%). Treatment with thiopurines was a risk factor for persistent elevated LFT (p = 0.029), steroids had a protective impact (p = 0.037). This study clearly highlights the importance of screening for hepatobiliary disorders and abnormal LFT in patients with UC, as the prevalence of hepatobiliary disorders and abnormal LFT is detected very often among this patient group.

Remdesivir: treatment of COVID-19 in special populations.

Remdesivir (RDV) is the mainstay antiviral therapy for moderate to severe COVID-19. Although remdesivir was the first drug approved for COVID-19, information about its efficacy and safety profile is limited in a significant segment of the population, such as people with underlying diseases, the elderly, children, and pregnant and lactating women. The efficacy and safety profile of RDV in disease progression, renal impairment, liver impairment, immunosuppression, geriatrics, pediatrics, pregnancy, and breastfeeding in COVID-19 patients was evaluated. The databases searched included Embase, Scopus, and PubMed. Only English language studies enrolling specific subpopulations with COVID-19 and treated with RDV were included. Thirty-nine clinical trials, cohorts, cross-sectional studies, and case series/reports were included. Most supported the benefits of RDV therapy for COVID-19 patients, such as lessening the duration of hospitalization, alleviating respiratory complications, and reducing mortality. Adverse effects of RDV, including liver and kidney impairment, were, for the most part, moderate to mild, supporting the safety profile of RDV therapy. RDV therapy was well tolerated, no new safety signals were detected, and liver function test abnormalities were the most common adverse events. Moreover, RDV, for the most part, was effective in managing the complications of COVID-19 and reducing mortality in these patients, except for patients with kidney impairment. Future studies, including RCTs, should include these subpopulations of patients to avoid delays associated with receiving proper medication through compassionate use programs.

Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study

IntroductionThere are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.MethodsDe-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.ResultsIn total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).ConclusionsThese real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact.

Derivation and validation of the BIMAST score for predicting the presence of fibrosis due to Metabolic dysfunction-associated steatotic liver disease among diabetic patients in the community.

Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care. Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime. Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST. The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients.

The Use of Antiepileptic Drug for Postcranioplasty Seizure: A Systematic Review and Meta-analysis

Introduction: Cranioplasty, a common procedure following craniectomy, aims to repair cranial defects resulting from various causes, including trauma and raised intracranial pressure. Despite its routine application, cranioplasty is associated with complications, notably seizures. The incidence of postcranioplasty seizures (PCS) and the role of antiepileptic drug (AED) prophylaxis remain underexplored. This meta-analysis aims to evaluate the impact of AED prophylaxis on both early and late PCS. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic literature search on PubMed, Europe PMC, ClinicalTrials.gov, and EMBASE, yielding 1292 articles. Eligibility criteria included randomized clinical trials (RCTs) in English reporting PCS incidence with or without AED prophylaxis. The risk of bias was assessed using Cochrane’s RoB 2 tool. Statistical analysis employed RevMan 5.4 software. Results: Of the initially identified articles, two RCTs met the inclusion criteria, involving a total of 497 cases. AED prophylaxis significantly reduced the risk of early PCS (risk ratio [RR]: 0.15, confidence interval [CI]: 0.06–0.37, P &lt; 0.0001), with no heterogeneity (I 2 = 0%, P = 0.78). However, there was no significant difference in late PCS incidence between the intervention and control groups (RR: 0.32, CI: 0.06–1.56, P = 0.16). No significant differences in abnormal liver function or blood test results were observed between groups. Conclusion: AED prophylaxis significantly reduces the risk of early PCS following cranioplasty, but its effectiveness in preventing late PCS remains uncertain. Further studies are warranted to determine optimal AED regimens and address the limitations of the current meta-analysis.

Epidemiological and Clinical Features of Rickettsial Infection Among Australian Individuals from 2015 to 2018

Objective: In this study, the clinical, laboratory and epidemiological features of rickettsial infection in Australian patients were examined. Methods: Patients with Rickettsia spp. seropositivity were selected from the database of the Australian Rickettsial Reference Laboratory. Questionnaires were sent to each referring physician with a request for information regarding the patient’s illness. Results: A retrospective analysis of 178 patients revealed the following common features in Australian rickettsial infection: fever, headache, myalgia, rash and a history of recent exposure to the Australian bush. The history included tick bites, eschar presence, respiratory abnormalities and acute fatigue, accompanied by abnormal haematology and liver function tests. Conclusions: A differential diagnosis including rickettsial infection should be confirmed (or refuted) by rickettsial serology.

Common variable immunodeficiency disorder-related liver disease is common and results in portal hypertension and an increased risk of death.

Common variable immunodeficiency disorder (CVID) manifests with recurrent infections and inflammatory complications, including liver disease. We report the clinical features, natural history, and outcomes of patients with CVID-related liver disease (CVID-rLD) from a tertiary immunology and hepatology center. Two hundred eighteen patients were identified; CVID-rLD was defined by persistently abnormal liver function tests or evidence of chronic liver disease (CLD) or portal hypertension (PHTN) by radiological or endoscopic investigation, after exclusion of other causes. Patients with CVID-rLD were investigated and managed following a joint pathway between immunology and hepatology services. Data, including clinical parameters, investigations, and outcomes, were retrospectively collected. A total of 91/218 (42%) patients had evidence of CVID-rLD, and 40/91 (44%) had PHTN. Patients with CVID-rLD were more likely to have other noninfectious complications of CVID (85/91, 93.4% vs. 75/127, 59.1%, p<0.001) including interstitial lung disease, gut disease, and autoimmune cytopenias. Nodular regenerative hyperplasia (NRH) was identified in 63.8% of liver biopsies, and fibrosis in 95.3%. Liver stiffness measurements (LSMs) were frequently elevated (median 9.95 kPa), and elevated LSM was associated with PHTN. All-cause mortality was higher in those with CVID-rLD (24/91, 26.4% vs. 14/127, 11%, p=0.003), which was the only organ complication associated with mortality (HR 2.24, 1.06-4.74, p=0.04). Factors predicting mortality in CVID-rLD included PHTN, increasing fibrosis, and LSM. Liver disease is a common complication of CVID as part of complex, multi-organ involvement and is associated with high rates of PHTN and an increased hazard of mortality.

Incidence, characteristics, and risk factors of new liver disorders 3.5 years post COVID-19 pandemic in the Montefiore Health System in Bronx.

To determine the incidence of newly diagnosed liver disorders (LD) up to 3.5-year post-acute COVID-19, and risk factors associated with new LD. We analyzed 54,699 COVID-19 patients and 1,409,547 non-COVID-19 controls from March-11-2020 to Jan-03-2023. New liver disorders included abnormal liver function tests, advanced liver failure, alcohol and non-alcohol related liver disorders, and cirrhosis. Comparisons were made with ambulatory non-COVID-19 patients and patients hospitalized for other lower respiratory tract infections (LRTI). Demographics, comorbidities, laboratory data, incomes, insurance status, and unmet social needs were tabulated. The primary outcome was new LD at least two weeks following COVID-19 positive test. Incidence of new LD was not significantly different between COVID-19 and non-COVID-19 cohorts (incidence:1.99% vs 1.90% p>0.05, OR = 1.04[95%CI: 0.92,1.17], p = 0.53). COVID-19 patients with new LD were older, more likely to be Hispanic and had higher prevalence of diabetes, hypertension, chronic kidney disease, and obesity compared to patients without new LD. Hospitalized COVID-19 patients had no elevated risk of LD compared to hospitalized LRTI patients (2.90% vs 2.07%, p>0.05, OR = 1.29[0.98,1.69], p = 0.06). Among COVID-19 patients, those who developed LD had fewer patients with higher incomes (14.18% vs 18.35%, p<0.05) and more with lower incomes (21.72% vs 17.23%, p<0.01), more Medicare and less Medicaid insurance, and more patients with >3 unmet social needs (6.49% vs 2.98%, p<0.001) and fewer with no unmet social needs (76.19% vs 80.42%, p<0.001). Older age, Hispanic ethnicity, and obesity, but not COVID-19 status, posed increased risk for developing new LD. Lower socioeconomic status was associated with higher incidence of new LD.