Abnormal Liver Function Tests Research Articles

Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study

Background: Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients. Methods: This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation. Results: In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%). The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p < 0.0001). Conclusions: Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.

Revised Clinical Practice Guideline of Korean Pancreatobiliary Association for Common Bile Duct Stones: Diagnosis

The diagnosis of common bile duct (CBD) stones is conducted through various imaging tests, endoscopic examinations, and the patient's clinical presentation. In patients with symptomatic gallstone disease, initial tests such as liver function tests, abdominal ultrasound, and abdominal computed tomography can be performed. Based on the results of these initial tests, symptomatic patient with cholelithiasis can be classified into low risk, intermediate risk, and high risk groups. Low risk of choledocholithiasis is characterized by normal liver function test results and absence of CBD dilation on abdominal ultrasound. For patients in this category, additional tests are not necessary unless symptoms indicating CBD stones persist. Intermediate risk of choledocholithiasis is identified by abnormal liver function test results or CBD dilation on abdominal ultrasound. Additional tests such as endoscopic ultrasound or magnetic resonance cholangiopancreatography can be performed. If CBD stones are confirmed in the additional tests, endoscopic retrograde cholangiopancreatography (ERCP) is required. High risk of choledocholithiasis is diagnosed when there is clinical evidence of cholangitis or CBD stones are identified on imaging tests. In such cases, ERCP is recommended for both diagnosis and treatment purposes without the need for further additional tests.

Optimising liver screening in patients with a Fontan circulation: a cost-effective approach to detection of Fontan associated liver disease which enhances patient care

Abstract Introduction Patients with Fontan circulation, require screening for liver cirrhosis and malignancy, to which they are susceptible with time. Surveillance biopsies reveal nearly all adult Fontan patients develop asymptomatic fibrosis, and a majority have abnormal liver function tests (LFTs). This presents significant financial healthcare burden and psychological stress with testing for patients. Objective We aim to present "real-world" liver screening data, from a leading Adult Congenital Heart Disease (ACHD) centre, to propose a cost-reducing testing regimen, which delivers effective screening, while taking account of the challenges of current guidance, patient compliance, and clinical practice. Methods We analysed liver screening data for Fontan patients at a leading ACHD centre, focusing on biochemical tests (bilirubin, ALT, GGT) and imaging. We evaluated the 10-year financial impact of current practices, versus a hypothetical model based on age and risk factors, alongside biannual and annual screening strategies. Tariffs for biochemical test were provided by the local pathology service and we used NHS HRG tariffs for imaging and phlebotomy. Results We included data from 114 patients with a Fontan circulation (median age 32 range 19-56, 42% females). Eighteen patients developed liver cirrhosis diagnosed on imaging (median age 32, range 22-48). None developed hepatocellular carcinoma. A lack of clear and agreed local screening guidelines (over years) resulted in vastly different investigations for FALD, with inconsistent time intervals for testing. Bilirubin was elevated in 59% (55% in age 18-29), ALT was elevated in 41% (31% in age 18-29), GGT was elevated in 83% (80% in age 18-29). We found 3 cases of cirrhosis in the age group 18-29, all with hypoplastic left heart; 4 cases of cirrhosis in age group 30-34 - all had significant comorbidities; 33% had normal bilirubin, LFT and GGT, potentially not requiring further screening until the age of 35. Eleven patients (22%) age 35+ had confirmed cirrhosis (Figure 1). Performing full FALD screening with biochemistry and liver ultrasound every 12-24 months would increase the cost of screening three- to six-fold. We propose rationalising liver screening by age and underlying risk (Figure 2) to minimise the economic burden and equally the psychological impact of frequent testing on patients. Conclusions Our analysis underscores the necessity for an optimised liver screening protocol in Fontan patients, balancing diagnostic accuracy with cost-efficiency. By integrating this data, we have identified a pathway to streamline screening, tailoring it to individual risk profiles and age groups, thereby reducing unnecessary tests, lowering costs and reducing the impact of testing on patients. This approach not only fosters better patient care, but also provides a framework for developing clearer, cost-effective screening guidelines, to monitor liver health, in these complex CHD patients.

Biomarkers of cardiohepatic syndrome in the cardiac intensive care unit

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Nonsteroidal anti-inflammatory drugs-associated vanishing bile duct syndrome: a real-world retrospective and disproportionality analysis

ABSTRACT Introduction Vanishing bile duct syndrome (VBDS) is a potentially fatal adverse reaction triggered by certain medications. The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and VBDS is based on case reports. We explored the reporting prevalence and evaluated the clinical features of NSAID-related VBDS. Research design and methods Adverse event reports of VBDS associated with NSAIDs from 2004 to 2023 in the FAERS database were retrieved, and disproportionality analyses were conducted to detect risk signals. Case reports from 2000 to 2023 on NSAID-induced VBDS were retrieved for retrospective analysis. Results We obtained 87 VBDS reports from the FAERS database. Ibuprofen had the greatest proportion of VBDS (63.2%), while loxoprofen had the highest positive signal value. Sixteen case reports showed evidence of VBDS, with 37.5% of children. The median age was 29 years; typical initial symptoms included rash (60.0%), jaundice (53.3%), fatigue/asthenia (33.3%), and SJS/TEN (53.3%). The median onset time of VBDS was 4 weeks. All cases had abnormal liver function tests, with the median level of TBIL being 20.0 mg/dl. The overall prognosis is poor, with 50% of patients achieving clinical remission. Conclusion Four NSAID agents had significant reporting associations with VBDS. Prescribers should be more aware of this risk and identify signs/symptoms earlier.

The effectiveness of liver function tests in the prediction of mortality in patients with COVID-19.

To evaluate the impact of liver function test abnormalities on mortality in critically ill coronavirus disease- 2019 patients. The single-centre, retrospective study was conducted at the Department of Anaesthesiology and Reanimation, Mersin City Training and Research Hospital, Turkiye, and comprised data from March 2020 to January 2022 of patients with positive real-time reverse transcription polymerase chain reaction test on nasopharyngeal swab sample for coronavirus disease-2019. Comorbidities, demographic data, admission to and discharge from the intensive care unit, Acute Physiology and Chronic Health Evaluation II scores, complete blood count on the first and second day of hospitalisation, coagulation parameters, biochemical analysis, 7-day, 28-day and total mortality of the patients in the intensive care unit were recorded. The patients were then divided into groups, with Group 1 having patients with normal liver enzymes, Group 2 having patients with abnormal liver enzymes, and Group 3 having patients with liver damage. Data was analysed using SPSS 20. Of the 940 subjects, 587(62.4) were males and 353(37.6) were females. The overall mean age of the patients was 67.11±16.65 years. There were 395(42%) patients in Group 1, 534(56.8%) in Group 2 and 11(1.2%) in Group 3. Gamma-glutamyl transferase-1s, aspartate aminotransferase-2nd and albumin-2nd were significant predictors of mortality (p<0.05). High gamma-glutamyl transferase, aspartate aminotransferase and low albumin levels in critically ill coronavirus disease-2019 patients could be considered indicators of high mortality rate.

Turmeric supplement-associated hepatitis: a clinicopathological series of 11 cases highlighting pan-lobular and zone 3 injury.

Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements. We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan-lobular and three zone 3-predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement-associated liver injury to be probable (eight cases) and possible (three). Histological features in the 'possible' cases were consistent with drug-induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over-the-counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric.

8113 Thyroid Storm in a Patient with Thyroid Nodule on Anticoagulation

Abstract Disclosure: R. Kulkarni: None. S.S. Krishnasamy: None. N. Mon: None. R. Downs: None. Background: There are very few case reports related to hyperthyroidism due to anticoagulation use. We describe a case, of a less common cause of hyperthyroidism due to hemorrhagic thyroiditis in a patient on anticoagulation and history of metastatic colon cancer. Clinical case: A 67-year-old white male with PMH significant for colon cancer with liver metastasis s/p exploratory laparotomy with sigmoid colectomy, end-colostomy with Hartman's pouch creation, pre-diabetes, recent left IJ &amp; axillary vein thrombus on Eliquis, and thyroid nodule; presented with complaints of shortness of breath, difficulty swallowing and dizziness. Other symptoms included weight loss, complaints of heart racing and generalized body aches. The patient had a recent admission for similar complaints and was newly diagnosed with left IJ/axillary vein thrombus and expanding hemorrhagic thyroid nodule on imaging. He was discharged on anticoagulation for the DVT with 2 week follow up for elective thyroidectomy for goiter. The patient was admitted to the ICU for worsened respiratory status needing ventilatory support and pressor support. Physical findings on admission included jaundice, sinus tachycardia, lethargy with agitation. Initial labs showed TSH 0.02 uIU/mL, FT4 4.85 ng/dL and FT3 6.8 pg/mL, LFTs &amp;gt;500 U/L. Burch-Wartofsky Point Scale score was &amp;gt;60 suggestive of thyroid storm. Imaging with PET CT was concerning for thyroid enlargement with multiple nodules with increased uptake. Thyroid US was consistent with heterogenous gland with hemorrhagic nodules. Based on clinical history, physical findings, diagnostic labs, and imaging the patient was diagnosed with severe hyperthyroidism with thyroid storm secondary to hemorrhagic thyroid nodules in the setting of anticoagulation. The patient underwent thyroid artery angiogram with particle embolization of left inferior and right superior thyroid arteries. Endocrinology started the patient on methylprednisolone, cholestyramine and propranolol. Thionamide was held since the patient had abnormal liver function tests in the setting of shock liver. The patient’s thyroid function slowly improved on current regimen to TSH 0.05 uIU/mL, FT4 1.7 ng/Dl and FT3 4.1 pg/mL on day 3. At the family interdisciplinary meeting, due to guarded prognosis, family opted for comfort care, and the patient finally succumbed to multiple co-morbidities. Conclusion: The case presented discusses diagnosis and management of less common causes of hyperthyroidism and management of thyroid storm in liver dysfunction. The patient would have needed a thyroid biopsy at a later date to rule out colonic metastasis as a cause of hemorrhage if he had survived the thyroid storm and comorbid illnesses. Presentation: 6/3/2024

6570 Treatment of Cushing’s With Levoketoconazole: A Case Series

Abstract Disclosure: N. Chamorro-Pareja: None. M. Haines: None. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Research Investigator; Self; Recordati, NovoNordisk, Perspectum Ltd, Lumos Pharma, Pfizer, Inc.. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. B.M. Biller: Consulting Fee; Self; Xeris Pharmaceuticals, Recordati Rare Diseases, Sparrow, Lundbeck. Background: Endogenous Cushing’s syndrome (CS) is a rare condition of excess cortisol secretion; the most common cause is a pituitary corticotroph tumor (Cushing’s disease [CD]). Medical treatment for CD is primarily used to control hypercortisolism in patients with persistent or recurrent disease after transsphenoidal surgery (TSS). Levoketoconazole (LKCZ), a steroidogenesis inhibitor, was FDA approved in January 2022 for CS treatment. This reports 3 cases of patients who were treated with LKCZ for recurrent CS. Clinical Cases: Case 1: 44-year-old (yo) male (M) with a history of CD with urinary free cortisol (UFC) &amp;gt;26x upper limit of normal (ULN) who was treated preoperatively with ketoconazole (KCZ) 1000 mg/day with UFC improved to 6x ULN. KCZ was discontinued at TSS, and he achieved remission post-operatively. He was lost to follow-up and re-presented after several years with worsening hypertension, muscle weakness, edema, and anxiety with UFC 28x ULN and a recurrent pituitary lesion on MRI. He declined repeat TSS and underwent radiation therapy (RT) and medical treatment. LKCZ was initiated at 150 mg twice daily (BID) and increased to 300 mg BID. At LKCZ 300 mg BID, he had a low UFC and mild nausea but an adequate serum morning cortisol (10.4 ug/dL, ref:6-18.4 ug/dL); LKCZ was reduced to 150 mg BID with resolution of symptoms (sxs) and normal UFC. Case 2: 56 yo M with a history of CD (UFC &amp;gt;3x ULN) who underwent 2 TSSs and RT over 10 years prior with eventual remission, but later recurred. Sxs included brain fog and mood disturbances. He achieved control with pasireotide but discontinued due to abnormal liver function tests. He was then treated with KCZ 400 mg/day but remained hypercortisolemic (LNSC 1.1x ULN) and was interested in trying a new medication, so was switched to LKCZ 150 mg BID with significant improvement of sxs and normalization of LNSC. Case 3: 54 yo F with presumed cyclic CD (negative whole-body and octreotide scans) with UFC 1.7x ULN and LNSC 3x ULN. TSS was performed with negative pathology; she had persistent hypercortisolemia and sxs including insomnia, fatigue, and mood disturbances. She was intolerant to and/or uncontrolled on 4 medications, including KCZ at 1000 mg/day that was discontinued due to a rash. She was started on LKCZ 150 mg BID and achieved normal LNSC and UFC after about 1 month. The drug was discontinued due to the development of a rash similar to that with KCZ. Conclusion: LKCZ is a new option for the treatment of CS in patients whose disease persists after TSS. These 3 patients had improvement of sxs and normalization of cortisol levels while on LKCZ, although one patient discontinued LKCZ due to a rash that was previously experienced with KCZ. The other two patients are being carefully monitored for liver function test elevation, QTc abnormalities and adrenal insufficiency with no issues to date. To our knowledge, this is the first case series of CS patients treated clinically with LKCZ. Presentation: 6/1/2024

Effects of Ursodeoxycholic Acid Treatment for Intrahepatic Cholestasis of Pregnancy on Maternal and Fetal Outcomes.

Intrahepatic cholestasis of pregnancy (ICP) appears in the second or third trimester of pregnancy and is characterized by pruritus and elevated blood bile acid (BA) levels. Complications from these symptoms may include preterm birth, fetal distress, or stillbirth. Although the precise causes of ICP are unknown, genetic, hormonal, and environmental variables may be involved. First-line treatment for ICP is ursodeoxycholic acid (UDCA), which improves bile flow and consequently lowers BA levels and pruritus. The objective of this study is to investigate the impact of UDCAtherapy on maternal and fetal outcomes in women with ICP. This was a prospective observational study of 123 pregnant women with ICP, aged between 20 and 45 years who were diagnosed clinically (pruritus) supported by abnormal laboratory results including elevated serum BA levels, and abnormalities in liver function tests, over the course of three years, from July 2021 to June 2024. Every patient received UDCA, commencing at 10-15 mg/kg/day and being titrated according to clinical guidelines. Maternal and fetal outcomes were tracked for the duration of the pregnancy, with data being collected at baseline (15 ± 1 weeks) and every two weeks until delivery. The mean age of the study participants was 29.6 ± 5.4 years, with the youngest patient being 20 years and the oldest being 45 years. Most womenwere multipara 65.9%, and the mean BMI was 27.8 ± 3.5 kg/m ². The mean time of gestational age at ICPdiagnosis was 31.2 ± 2.7 weeks, and the time of gestational age at delivery was 37.1 ± 2.4 weeks. On average, the serum BA level at diagnosis was 23.5 ± 8.1 µmol/L. In the majority of ICP patients with good fetal outcomes, UDCA not only normalizes serum BA levels but also reduces maternal symptoms. In addition to addressing patient response variability to this therapy and optimizing dissemination procedures, the researchers expect that the results of this study will support the continued use of UDCA as first-line treatment for ICP, at least until more evidence becomes available.

A Classical Manifestation of Eosinophilic Granulomatosis with Polyangiitis with an Unusual Catastrophic Outcome

A 57-year-old male patient, with a known case of bronchial asthma presented with acute dyspnea, cough with expectoration, fever, severe myalgia, and pedal edema. On physical examination, he had tachypnea, high temperature, bilateral polyphonic rhonchi, audible wheeze, and asymmetric sensory and motor neuropathy. Cutaneous examination revealed multiple palpable purpuric lesions with few hemorrhagic bullae and crusted erosions distributed symmetrically over bilateral limbs suggestive of cutaneous small vessel vasculitis. Investigations showed elevated total counts, eosinophilia, deranged electrolytes, and abnormal liver and renal function tests. Histopathology revealed eosinophilic predominant vasculitis. Testing for perinuclear anti-cytoplasmic antibody was positive. A diagnosis of eosinophilic granulomatosis with polyangiitis (Churg–Strauss disease) was thus confirmed. The patient succumbed in 2 weeks due to multi-organ failure. All the characteristic findings were found in our patient, but a fatal outcome in a very short period after diagnosis was an unusual presentation.

Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis. The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed. Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES. These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.

Artificial Intelligence in Identifying Patients With Undiagnosed Nonalcoholic Steatohepatitis.

Background: Although increasing in prevalence, nonalcoholic steatohepatitis (NASH) is often undiagnosed in clinical practice. Objective: This study identified patients in the Veterans Affairs (VA) health system who likely had undiagnosed NASH using a machine learning algorithm. Methods: From a VA data set of 25 million adult enrollees, the study population was divided into NASH-positive, non-NASH, and at-risk cohorts. We performed a claims data analysis using a machine learning algorithm. To build our model, the study population was randomly divided into an 80% training subset and a 20% testing subset and tested and trained using a cross-validation technique. In addition to the baseline model, a gradient-boosted classification tree, naïve Bayes, and random forest model were created and compared using receiver operator characteristics, area under the curve, and accuracy. The best performing model was retrained on the full 80% training subset and applied to the 20% testing subset to calculate the performance metrics. Results: In total, 4 223 443 patients met the study inclusion criteria, of whom 4903 were positive for NASH and 35 528 were non-NASH patients. The remainder was in the at-risk patient cohort, of which 514 997 patients (12%) were identified as likely to have NASH. Age, obesity, and abnormal liver function tests were the top determinants in assigning NASH probability. Conclusions: Utilization of machine learning to predict NASH allows for wider recognition, timely intervention, and targeted treatments to improve or mitigate disease progression and could be used as an initial screening tool.

Artificial Intelligence in Identifying Patients With Undiagnosed Nonalcoholic Steatohepatitis

Background: Although increasing in prevalence, nonalcoholic steatohepatitis (NASH) is often undiagnosed in clinical practice. Objective: This study identified patients in the Veterans Affairs (VA) health system who likely had undiagnosed NASH using a machine learning algorithm. Methods: From a VA data set of 25 million adult enrollees, the study population was divided into NASH-positive, non-NASH, and at-risk cohorts. We performed a claims data analysis using a machine learning algorithm. To build our model, the study population was randomly divided into an 80% training subset and a 20% testing subset and tested and trained using a cross-validation technique. In addition to the baseline model, a gradient-boosted classification tree, naïve Bayes, and random forest model were created and compared using receiver operator characteristics, area under the curve, and accuracy. The best performing model was retrained on the full 80% training subset and applied to the 20% testing subset to calculate the performance metrics. Results: In total, 4 223 443 patients met the study inclusion criteria, of whom 4903 were positive for NASH and 35 528 were non-NASH patients. The remainder was in the at-risk patient cohort, of which 514 997 patients (12%) were identified as likely to have NASH. Age, obesity, and abnormal liver function tests were the top determinants in assigning NASH probability. Conclusions: Utilization of machine learning to predict NASH allows for wider recognition, timely intervention, and targeted treatments to improve or mitigate disease progression and could be used as an initial screening tool.

Prevalence of Hepatitis C in Liver Cirrhosis Patients

Background: Hepatitis C Virus (HCV) is a major cause of chronic liver disease, including liver cirrhosis, globally. Identifying the prevalence of HCV among cirrhotic patients can improve clinical outcomes and guide management strategies.Objective: To determine the prevalence of HCV in patients with liver cirrhosis and assess the association between liver enzyme levels (ALT and AST) and HCV infection.Methods: This retrospective observational study was conducted at Fatima Memorial Hospital, Lahore, from June 2023 to December 2023. Fifty liver cirrhosis patients with abnormal liver function tests were included. HCV infection was evaluated using ELISA for antibodies and PCR for RNA detection. Data analysis was performed using IBM SPSS version 25.0, with a p-value of &lt;0.05 considered significant.Results: Among 50 cirrhotic patients, 60% tested positive for HCV antibodies via ELISA, and 46% were confirmed positive by PCR. Mean ALT levels were significantly higher in ELISA-positive (867 U/L) and PCR-positive (1096.43 U/L) patients compared to ELISA-negative (42 U/L) and PCR-negative (59.96 U/L) patients (p &lt; 0.001).Conclusion: A significant prevalence of HCV was observed among liver cirrhosis patients, with elevated ALT and AST levels indicating liver damage associated with HCV infection.

Long-Term Safety and Efficacy of Janus kinase (JAK) Inhibitors in the Treatment of Rheumatoid Arthritis

Background: Janus kinase (JAK) inhibitors are a new class of drugs for the treatment of rheumatoid arthritis (RA); however, the long-term consequences of using these drugs are still not well understood. Objective: The primary objective of this research was to examine the effectiveness and safety of JAK inhibitors for the management of rheumatoid arthritis (RA) patients. Methodology: Clinical raw data of 150 RA patients receiving JAK inhibitors was collected in different tertiary care hospitals in Lahore, Pakistan from March 2023 to June 2024. till were conducted. The anti-inflammatory effect was evaluated by the Disease Activity Score in 28 joints (DAS28) and the safety profile through adverse events, laboratory markers, and patients self-reported outcomes. The SPSS version 27 applied for raw data analysis which used the paired t-tests and multiple regression models to establish the factors that determine favorable outcomes and complications. Results: JAK inhibitors also reduced the DAS28 scores from baseline to 24 months by a mean of 3. 2 ± 1. 1 (p&lt;0. 001). The findings stated that 12 percent of the patients at baseline and 45 percent of the patients at 24 months had achieved remission. The reported side effects were infections, 25%; gastrointestinal problems, 18%; and abnormal liver function tests, 10%. Severe adverse reactions were noted in 5% of the patients and no new safety issues were observed over the course of the treatment. Conclusion: JAK inhibitors have been shown to be useful in decreasing the activity of RA for the long-term use with reasonable side effects. The results provided evidence that JAK inhibitors were best treatment of rheumatoid arthritis (RA) but for best efficacy results closely monitoring and specific approach should be applied.

Prognostic Values of Ferroptosis-Related Proteins ACSL4, SLC7A11, and CHAC1 in Cholangiocarcinoma.

The epithelial malignant tumor known as cholangiocarcinoma (CCA) is most commonly found in Southeast Asia, particularly in northeastern Thailand. Previous research has indicated that the overexpression of acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and ChaC glutathione-specific γ-glutamylcyclotransferase (CHAC1) as ferroptosis-related proteins is associated with poorer prognosis in several cancers. The role of these three proteins in CCA is still unclear. The present study aimed to investigate the expression levels of ACSL4, SLC7A11, and CHAC1, all potential ferroptosis biomarkers, in CCA. The ACSL4, SLC7A11, and CHAC1 protein expression levels in 137 CCA tissues were examined using immunohistochemistry, while 61 CCA serum samples were evaluated using indirect ELISA. The associations between the expression levels of ACSL4, SLC7A11, and CHAC1 and patient clinicopathological data were evaluated to determine the clinical significance of these proteins. The expression levels of ACSL4, SLC7A11, and CHAC1 were assessed in CCA tissues. A significant association was observed between high ACSL4 levels and extrahepatic CCA, tumor growth type, and elevated alanine transferase (ALT). There was also a positive association between elevated SLC7A11 levels and tumor growth type. Additionally, the upregulation of CHAC1 was significantly associated with a shorter survival time in patients. High levels of ACSL4 and SLC7A11 in CCA sera were both significantly associated with advanced tumor stages and abnormal liver function test results, indicating that they could be used as a reliable prognostic biomarker panel in patients with CCA. The results of the present study demonstrated that the upregulation of ACSL4, SLC7A11, and CHAC1 could be used as a valuable biomarker panel for predicting prognosis parameters in CCA. Furthermore, ACSL4 and SLC7A11 could potentially serve as complementary markers for improving the accuracy of prognosis prediction when CCA sera is used. These less invasive biomarkers could facilitate effective treatment planning.

Assessment of abnormal liver function tests and associated factors among COVID-19-infected patients in Addis Ababa, Ethiopia, 2022: a facility-based comparative cross-sectional study

ObjectiveLiver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities...

Clinical Characteristics, Nutritional Status, and Disease Severity in Pediatric Patients with COVID-19

Background: Limited clinical data are available regarding the impact of coronavirus disease 2019 (COVID-19) on children. Objective: This study assessed the clinical characteristics, nutritional status, and disease severity in pediatric patients with COVID-19. Methods: A retrospective study examined medical records of children with COVID-19 admitted to Abuzar Hospital (Ahvaz, Iran) for six months. Data related to their clinical, nutritional status and demographic characteristics were documented. Results: This study included medical records of 500 patients. More than half of them were boys. Different levels of COVID-19 severity were observed in 202, 172, and 126 children as mild, moderate, and severe cases, respectively. Children with severe or moderate COVID-19 had substantially elevated levels of various inflammatory markers, blood urea nitrogen (BUN), gamma-glutamyl transferase (GGT), neutrophils, alanine transaminase (ALT), creatinine, bilirubin, and aspartate aminotransferase (AST) compared to those with mild COVID-19 (p &lt; 0.001). They had lower levels of lymphocytes and vitamin D, as well as longer hospital stays than children with mild COVID-19 (p &lt; 0.001). In addition, 52% and 40.2% of patients had malnutrition and anemia, respectively. The majority of underweight and stunted children had moderate or severe COVID-19. Conclusion: This study revealed a high prevalence of malnutrition, anemia, insufficient levels of vitamin D, elevated levels of inflammatory markers, and abnormal liver and kidney function tests in children with severe or moderate cases of COVID-19 compared to those with mild COVID-19.

Occurrence of liver abscess in patients with acute prostatitis.

Liver abscesses concomitant with acute prostatitis are rare and potentially fatal. We analyzed the occurrence of this condition and clinical characteristics of the affected patients. The medical records of 474 patients diagnosed with acute prostatitis between June 2006 and July 2022 were retrospectively reviewed. Patients in whom pathogens were not detected in serum or urine cultures were excluded. A total of 271 patients were included in the analysis. Patient characteristics and laboratory test results were compared between patients with acute prostatitis with and without liver abscesses. Fifteen patients (5.5%) were identified with simultaneous liver abscesses and acute prostatitis. The liver abscess group was younger than the non-liver abscess group in terms of mean age. In the univariate analysis, a high proportion of patients had diabetes mellitus, whereas a low proportion had hypertension. None of the underlying diseases, including benign prostatic hyperplasia, malignancy, or alcoholism, demonstrated a significant association with liver abscess in multivariate analysis; however, an association was observed in liver function test results. All patients with liver abscesses tested positive for Klebsiella pneumoniae. When K. pneumoniae is identified in patients with acute prostatitis and abnormal liver function tests, considering the possibility of metastatic infection in other organs, including the liver, and performing an active evaluation is essential.