Liver Chemistry Research Articles

Initial outcomes of a dedicated multidisciplinary non-alcoholic fatty liver disease clinic: a retrospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is a major healthcare burden. Real-world outcomes in dedicated tertiary care settings in Australia remain unknown. To evaluate the initial outcomes of patients referred to a dedicated multidisciplinary tertiary care NAFLD clinic. Retrospective review of all adult patients with NAFLD who attended a dedicated tertiary care NAFLD clinic between January 2018 and February 2020 and who had two clinic visits and FibroScans at least 12 months apart. Demographic and health-related clinical and laboratory data were extracted from electronic medical records. Key outcome measures were serum liver chemistries, liver stiffness measurement (LSM) and weight control at 12 months. A total of 137 patients with NAFLD were included. Median (interquartile range (IQR)) follow-up time was 392 days (343-497 days). One hundred and eleven patients (81%) achieved weight control (i.e. weight loss or stability). Markers of liver disease activity were significantly improved, including median (IQR) serum alanine aminotransferase (48 (33-76) vs 41 (26-60) U/L, P=0.009) and aspartate aminotransferase (35 (26-54) vs 32 (25-53) U/L, P=0.020). Median (IQR) LSM across the whole cohort was significantly improved (8.4 (5.3-11.8) vs 7.0 (4.9-10.1) kPa, P=0.001). No significant reduction was observed in mean body weight or the frequency of metabolic risk factors. This study highlights a new model of care for patients with NAFLD and demonstrates promising initial outcomes in relation to significant reductions in markers of liver disease severity. Although most patients achieved weight control, further refinements are needed to achieve significant weight reduction including more frequent and structured dietetic and/or pharmacotherapeutic interventions.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

BackgroundAcute liver failure (ALF) is an unpredictable and life-threatening critical illness. The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure. MethodsAnimals were divided into 3 groups, normal, thioacetamide (TAA, ALF model) and TAA + AGK2. Cultured L02 cells were divided into 5 groups, normal, TAA, TAA + mitofusin 2 (MFN2)-siRNA, TAA + AGK2, and TAA + AGK2 + MFN2-siRNA groups. The liver histology was evaluated with hematoxylin and eosin staining, inositol-requiring enzyme 1 (IRE1), activating transcription factor 6β (ATF6β), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylated-PERK (p-PERK). C/EBP homologous protein (CHOP), reactive oxygen species (ROS), MFN2 and glutathione peroxidase 4 (GPX4) were measured with Western blotting, and cell viability and liver chemistry were also measured. Mitochondria-associated endoplasmic reticulum membranes (MAMs) were measured by immunofluorescence. ResultsThe liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis, which were reduced by AGK2 pre-treatment. In comparison to the normal group, apoptosis rate and levels of IRE1, ATF6β, p-PERK, CHOP, ROS and Fe2+ in the TAA-induced ALF model group were significantly increased, which were decreased by AGK2 pre-treatment. The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group, which were enhanced by AGK2 pre-treatment. Compared with the TAA-induced L02 cell, apoptosis rate and levels of IRE1, ATF6β, p-PERK, CHOP, ROS and Fe2+ were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group. AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1, ATF6β, p-PERK, CHOP, ROS and Fe2+ and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell. Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells. ConclusionsThe data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Variations in Biochemical Parameters in Diabetic and Non-Diabetic Patients of Septicemia

Septicemia is an infection caused by poisoning of blood by bacteria and is a prevalent disease in Pakistan. However, there is limited understanding of the pathogenesis of abnormal blood, liver and renal chemistry tests in septicemia. Objective: To determine variations in respective LFTs and RFTs and CBCs of diabetic and non-diabetic patients of septicemia. Methods: A descriptive, observational, cross-sectional research was directed, involving 101 participants diagnosed with septicemia. Study setting was Mayo Hospital Lahore. A specially designed Performa was used to record data, including liver function tests, renal function tests, and complete blood count for each patient. The data were analyzed using the latest version of SPSS. Results: In this study 45/101 patients of septicemia had diabetes. LFTs were also same for both non-diabetic and diabetic patients except Albumin which was low in diabetic patients but normal in non-diabetic patients. CBC were equally deranged in all diabetic and non-diabetic patients. Conclusions: This research provides important understandings into the variations of LFTs and RFTs and CBCs in diabetic and non-diabetic patients with septicemia. The findings suggest that while LFTs are similar between the two groups, there is a difference in albumin levels, highlighting the need for further investigation into the role of diabetes in septicemia.

Liver injury associated with the severity of COVID-19: A meta-analysis.

The current 2019 novel coronavirus disease (COVID-19) pandemic is a major threat to global health. It is currently uncertain whether and how liver injury affects the severity of COVID-19. Therefore, we conducted a meta-analysis to determine the association between liver injury and the severity of COVID-19. A systematic search of the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2022, was performed to analyse the reported liver chemistry data for patients diagnosed with COVID-19. The pooled odds ratio (OR), weighted mean difference (WMD) and 95% confidence interval (95% CI) were assessed using a random-effects model. Furthermore, publication bias and sensitivity were analyzed. Forty-six studies with 28,663 patients were included. The pooled WMDs of alanine aminotransferase (WMD = 12.87 U/L, 95% CI: 10.52-15.23, I 2 = 99.2%), aspartate aminotransferase (WMD = 13.98 U/L, 95% CI: 12.13-15.83, I 2 = 98.2%), gamma-glutamyl transpeptidase (WMD = 20.67 U/L, 95% CI: 14.24-27.10, I 2 = 98.8%), total bilirubin (WMD = 2.98 μmol/L, 95% CI: 1.98-3.99, I 2 = 99.4%), and prothrombin time (WMD = 0.84 s, 95% CI: 0.46-1.23, I 2 = 99.4%) were significantly higher and that of albumin was lower (WMD = -4.52 g/L, 95% CI: -6.28 to -2.75, I 2 = 99.9%) in severe cases. Moreover, the pooled OR of mortality was higher in patients with liver injury (OR = 2.72, 95% CI: 1.18-6.27, I 2 = 71.6%). Hepatocellular injury, liver metabolic, and synthetic function abnormality were observed in severe COVID-19. From a clinical perspective, liver injury has potential as a prognostic biomarker for screening severely affected patients at early disease stages. https://www.crd.york.ac.uk/prospero/, Identifier: CRD42022325206.

Liver Injury Patterns and Hepatic Toxicity among People Living with and without HIV and Attending Care in Urban Uganda.

The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests. Among people living with and without HIV and attending care, we used the R ratio to evaluate for liver injury patterns. Liver injury patterns were defined as cholestatic (R < 2), mixed (R = 2-5), and hepatocellular (R > 5). Overall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR = 4.9 CI (1.0-24.2); p = 0.054), mixed liver injury (OR = 5.3 CI (1.1-27.3); p = 0.043), and hepatocellular liver injury (OR = 13.2 CI (1.0-167.3); p = 0.046)). Increasing age was associated with cholestatic liver injury among participants with HIV (OR = 2.3 CI (1.0-5.3); p = 0.038). Despite a high hepatitis B prevalence among participants with HIV, there was no association with liver injury. Liver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively.

Liver injury on admission linked to worse outcomes in COVID-19: an analysis of 14,138 patients.

Infection with the SARS-CoV-2 virus, which can result in hepatic inflammation and injury that varies from mild to severe and potentially acute fulminant liver injury, may be associated with poor outcomes. Our aims were to: (I) assess baseline clinical and demographic characteristics in patients with coronavirus disease 2019 (COVID-19) who did and did not have abnormalities in liver chemistries [alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (Tbili)] and (II) evaluate associations between abnormalities in liver chemistries and the primary outcomes of in-hospital death, intubation, and hospital length of stay (LOS). In this nationwide retrospective cohort study of 14,138 patients, we analyzed associations between abnormalities in liver chemistries (ALT, AST, ALP, and Tbili) and mortality, intubation, and prolonged hospital LOS in patients with laboratory-confirmed COVID-19. We used Pearson's chi-squared tests to detect significant differences in categorical variables for patients with and without abnormal liver chemistries. Welch's two-sample t-tests were used to make comparisons of liver chemistry (ALT, AST, ALP, Tbili) and serum albumin results. All other continuous variables were analyzed using independent samples t-tests. A P value of <0.05 was considered significant. Propensity score matching demonstrated that abnormalities in liver chemistries at admission are significantly associated with increased risk for mortality (RR 1.70) and intubation (RR 1.44) in patients with COVID-19. Elevated AST is the liver chemistry abnormality associated with the highest risk for mortality (RR 2.27), intubation (RR 2.12), and prolonged hospitalization (RR 1.19). Male gender, pre-existing liver disease, and decreased serum albumin are also significantly associated with severe outcomes and death in COVID-19. Routine liver chemistry testing should be implemented and used for risk stratification at the time of COVID-19 diagnosis.

Liver chemistries in severe or non-severe cases of COVID-19: A systematic review and meta-analysis

Coronavirus disease (COVID-19) patients exhibit different patterns of liver impairment, according to growing evidence. In this study, we sought to provide a comprehensive analysis of liver test parameters in patients with severe and non-severe COVID-19. We performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19. We searched PubMed, Google Scholar, Embase, Cochrane Library, medRxiv, bioRxiv, and three Chinese electronic databases through April 18, 2020, in accordance with the Preferred Reporting Items for Meta-Analyses. We analyzed pooled data on liver chemistries stratified by COVID-19 severity using a fixed or random-effects model. A meta-analysis of 56 studies, including 11052 patients, found that the pooled mean alanine aminotransferase (ALT) in severe COVID-19 cases was 35.9 IU/L whereas in non-severe COVID-19 cases was 27.3 IU/L. Average aspartate aminotransferase (AST) levels were 44.3 IU/L in severe cases compared to 27.9 IU/L in non-severe cases. In addition, AST levels are often higher than ALT levels regardless of disease severity. The severe cases tended to have a higher gamma-glutamyltransferase level but a lower albumin level than the non-severe cases. Severe COVID-19 was more likely to be associated with abnormal liver test results. Monitoring liver chemistry closely can help detect disease progression early.

Standard Venipuncture vs a Capillary Blood Collection Device for the Prospective Determination of Abnormal Liver Chemistry.

Abnormal liver function is a common manifestation of human disease and may also occur in approved and investigational medications as drug-induced liver injury (DILI). Capillary blood collection devices may allow for more frequent and convenient measurement outside of the clinic. Validation of such approaches is lacking. This prospective, biospecimens collection study evaluated the Tasso+ in patients with abnormal liver tests (NCT05259618). The primary objective was to define the concordance of alanine aminotransferase (ALT) obtained via Tasso+ compared to standard venipuncture. Secondary objectives included measurement of 14 other analytes and patient surveys. At the time of venipuncture, 2 Tasso+ samples were collected: one was centrifuged and shipped, and the other was refrigerated and shipped as whole blood. Thirty-six patients with elevated ALT values were enrolled. In total, 100 venipuncture, 50 Tasso+ centrifuged, and 48 Tasso+ whole blood samples were obtained. Tasso+ centrifuged samples demonstrated concordance correlation coefficients (CCC) of >0.99 for ALT, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and total bilirubin and CCC >0.95 for albumin, chloride, enzymatic creatinine, serum glucose, magnesium, and phosphorus. Tasso+ whole blood showed CCC of >0.99 for AST, bilirubin total, and enzymatic creatinine and CCC >0.95 for ALT, ALP, albumin, magnesium, and phosphorus. Hemolysis was comparable across the 3 sample types, but its impact was reflected in the Tasso+ potassium data. Patient feedback indicated a very favorable patient experience. The capillary blood collection device, Tasso+, showed substantial to almost perfect concordance to standard venipuncture for measurement of abnormal liver function. Studies are ongoing to validate longitudinal sampling outside of the clinic. Clinicaltrials.gov Registration Number: NCT05259618.

Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave

The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 vaccine-matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS-CoV-2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p < .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150-150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300-300 mg dose (p=.025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.

Association of Liver Fibrosis with Cognitive Test Performance and Brain Volume Changes in the UK Biobank Study

AbstractBackgroundLiver fibrosis is a chronic liver condition that, though frequently subclinical, has widespread systemic effects. We hypothesized that liver fibrosis is associated with worse cognitive performance and corresponding brain imaging changes.MethodWe examined the association of liver fibrosis with cognition and brain volumes among adults in the UK Biobank study, which prospectively enrolled approximately 500,000 people starting in 2007 and subsequently collected cognitive test and brain MRI data for some participants. We included participants with available liver fibrosis, cognitive test, and brain imaging data. Liver fibrosis was defined at baseline using validated cutoffs of the Fibrosis‐4 (FIB‐4) liver fibrosis score. The primary cognitive test outcome was the Digit Symbol Substitution Test (DSST), a multidomain test. Secondary cognitive test outcomes were executive function tests (Trails A, Trails B, Reaction Time) and memory tests (Numeric Memory, Pairs Matching). The primary imaging outcome was white matter hyperintensity volume; secondary outcomes were hippocampal volume and total brain volume. We used multiple linear regression models to evaluate the association of liver fibrosis with cognitive test performance and brain volumes while adjusting for potential confounders.ResultsAmong 105,313 participants with cognitive test data, the mean age was 56.1 years and 56% were women. Standard liver chemistries were largely in the normal range. However, 2.0% (95% CI, 1.9‐2.1%) had liver fibrosis based on FIB‐4 scores. Cognitive tests were completed a median of 5.8 years after baseline liver fibrosis assessment. After adjusting for demographics, socioeconomics, education, body mass index, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with worse performance on the DSST (β = ‐0.40; 95% CI, ‐0.60, ‐0.20; P&lt;0.001) (Figure). Liver fibrosis was associated with worse executive function but not memory test performance (Table). We included 34,730 participants with brain MRI, obtained a median of 9.3 years after baseline. In adjusted models, liver fibrosis was associated with lower hippocampal volume (β = ‐58.8; 95% CI, ‐94.7, ‐22.9; P = 0.001) and higher white matter hyperintensity volumes (β = 1142.8; 95% CI, 311.6, 1973.9; P = 0.007) (Table, Figure).ConclusionLiver fibrosis is associated with worse cognitive performance, perhaps explained by hippocampal volume loss and white matter hyperintensity burden.

Duodenal Dual-Wavelength Photobiomodulation Improves Hyperglycemia and Hepatic Parameters with Alteration of Gut Microbiome in Type 2 Diabetes Animal Model.

Recently, the duodenum has garnered interest for its role in treating metabolic diseases, including type 2 diabetes (T2DM). Multiple sessions of external photobiomodulation (PBM) in previous animal studies suggested it resulted in improved hyperglycemia, glucose intolerance, and insulin resistance with a multifactorial mechanism of action, despite the target organ of PBM not being clearly proven. This study aimed to determine whether a single session of a duodenal light-emitting diode (LED) PBM may impact the T2DM treatment in an animal model. Goto-Kakizaki rats as T2DM models were subjected to PBM through duodenal lumen irradiation, sham procedure, or control in 1-week pilot (630 nm, 850 nm, or 630/850 nm) and 4-week follow-up (630 nm or 630/850 nm) studies. Oral glucose tolerance tests; serum glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, and insulin levels; liver chemistry and histology; and gut microbiome in the PBM, sham control, and control groups were evaluated. In the 1-week study, duodenal dual-wavelength (D, 630/850 nm) LED PBM showed improved glucose intolerance, alkaline phosphatase and cholesterol levels, and weight gain than other groups. The D-LED PBM group in the 4-week study also showed improved hyperglycemia and liver enzyme levels, with relatively preserved pancreatic islets and increased serum insulin and GLP-1 levels. Five genera (Bacteroides, Escherichia, Parabacteroides, Allobaculum, and Faecalibaculum) were significantly enriched 1 week after the D-LED PBM. Bacteroides acidifaciens significantly increased, while Lachnospiraceae significantly decreased after 1 week. A single session of D-LED PBM improved hyperglycemia and hepatic parameters through the change of serum insulin, insulin resistance, insulin expression in the pancreatic β-cells, and gut microbiome in T2DM animal models.

Primary sclerosing cholangitis-A long night's journey into day.

Content available: Audio Recording.

Outcome of COVID-19 Patients Presented with Gastrointestinal and Hepatic Manifestations

Background. COVID-19 is rapidly spreading as a global pandemic disease that affects mortality, morbidity, and economic recession worldwide including Myanmar. This study is aimed at investigating the prevalence and temporal nature of gastrointestinal and hepatic manifestations as well as their association with composite clinical endpoints in patients with COVID-19. Method. This was a retrospective hospital-based cohort study conducted on confirmed COVID-19 patients who were admitted to two designated COVID-19 hospitals: DSLH and No. (22/100) MH, Yangon, Myanmar, from June 1, 2021, to August 31, 2021. Data related to patients’ demographics, clinical characteristics, and clinical outcomes were abstracted manually through individual hospital records. Results. Out of the 241 patients recruited, 68 (28.2%) of the patients had GI symptoms. Ageusia/hypogeusia and diarrhea are the most common symptoms at 41.3% and 28.3%, respectively. Abnormal liver chemistries at admission are found in 52.7% of total patients. Mortality is 12.9% (31/241). Patients with abnormal liver chemistry are older ( p &lt; 0.001 ), unvaccinated or incompletely vaccinated ( p = 0.04 ), associated comorbidities ( p = 0.019 ), leukocytosis ( p &lt; 0.001 ), lymphopenia ( p = 0.033 ), hypoalbuminemia ( p &lt; 0.001 ), higher INR ( p &lt; 0.001 ), and longer HDU stay ( p &lt; 0.001 ) and higher mortality ( p &lt; 0.001 ). Conclusion. COVID-19-infected patients with abnormal liver chemistry are found to have worse clinical outcomes, although no significant association is found in patients with digestive symptoms. More attention should be given to this group of patients in the next coming wave.

S3081 Newfound Glow: The First Reported Case of Drug-Induced Liver Injury Due to Tofacitinib

Introduction: Tofacitinib, a Janus kinase (JAK) inhibitor, is a medication used to treat autoinflammatory conditions. It has previously been associated with mild hepatocellular liver enzyme elevations, but here we describe the first reported case of a clinically apparent drug-induced liver injury (DILI) related to tofacitinib. Case Description/Methods: A 29-year-old man with ulcerative colitis developed jaundice, malaise, anorexia, abdominal pain, diarrhea, and pruritus six months after starting tofacitinib. His only other medication was lisinopril. He consumes less than three alcoholic drinks weekly. Liver chemistries revealed aspartate aminotransferase (AST) 635 IU/L, alanine aminotransferase (ALT) 614 IU/L, alkaline phosphatase (ALP) 150 IU/L, total bilirubin (T-Bili) 3.2 mg/dL, and direct bilirubin (D-Bili) 1.7 mg/dL. Coagulation studies were normal. Abdominal ultrasound showed a diffusely hypoechoic liver and a diffusely thickened gallbladder wall but no biliary pathology. He stopped taking tofacitinib, and his liver chemistries peaked at AST 826 IU/L, ALT 1427 IU/L, ALP 182 IU/L, and T-Bili 6.5 mg/dL. Anti-smooth muscle antibody was slightly positive at 41. Additional workup included negative antinuclear antibody and negative serologies for cytomegalovirus, Epstein-Barr virus, and hepatitis A, B, and C. His symptoms improved, and he resumed tofacitinib two months after symptom onset. Four months later, the patient’s symptoms recurred and labs redemonstrated acute liver injury with a new peak of T-Bili 9.1 mg/dL. Liver biopsy revealed acute hepatitis with diffuse severe hepatocanalicular cholestasis, inflammation, and necrosis, consistent with DILI. He stopped taking tofacitinib, and after one month his symptoms resolved and liver chemistries normalized. He was transitioned to vedolizumab and has remained asymptomatic. (Figure) Discussion: This patient developed a clinically apparent liver injury with jaundice six months after initiating therapy with tofacitinib for ulcerative colitis. Other causes, such as viral hepatitis, alcohol-related liver disease, and autoimmune hepatitis, were ruled out. Biopsy results were consistent with DILI, and he was on no other culprit medications. He was rechallenged with tofacitinib and redeveloped liver injury, strongly supporting the diagnosis of tofacitinib-induced DILI. The mechanism of liver injury is not fully understood but might be attributed to drug metabolism via CYP3A4. More research should be conducted to better elucidate the mechanism of liver injury by tofacitinib.Figure 1.: Liver biopsy with acute hepatitis, severe hepatocanalicular cholestasis, inflammation, and necrosis, as well as a multinucleated hepatocyte, consistent with drug-induced liver injury in the setting of tofacitinib use.

S3241 A Case of Autoimmune Hepatitis in the Setting of the Janssen COVID-19 Vaccine

Introduction: Autoimmune hepatitis (AIH) is an inflammatory autoimmune condition that can result in chronic liver disease, it can be caused by the interaction of hereditary, epigenetic, immune, and environmental triggers. Vaccine related AIH is an uncommon phenomenon that has been reported in the presence of other vaccinations.. We present a unique case of AIH in the setting of the Janssen SARS-CoV-2 vaccine (JJ). Case Description/Methods: A 45-year-old female with a history ofHTN, DM, GERD, and obesity presented from her primary care physician’s office with abnormal liver chemistries in a hepatocellular pattern. Her hepatic profile showed AST 1119, ALT 988, AP 130, and total bilirubin of 1.5 (R-factor 22.8). Given the magnitude and rapidity of the elevated chemistries a broad serologic workup was initiated. She was negative for hepatitis A, B, and C, as well as HSV 1/2, EBV, CMV, HIV, VZV, and adenovirus. Her ferritin and iron studies did not suggest iron overload. Her ceruloplasmin and alpha 1 antitrypsin levels were within acceptable ranges. Her ANA was negative; her smooth muscle antibody was positive (1:320), IgG was elevated to 3,451 mg/dL. Her urine toxin screen was negative. She had chronically been on HCTZ and took occasionally seamoss supplements. She denied using tylenol or any other over the counter or herbal supplements. In the past month she had received a single dose of the Janssen SARS CoV-2 vaccination (Johnson and Johnson). Her liver chemistries prior were AST 17, ALT 14, AP 52, and total bilirubin of 0.3. She subsequently underwent a liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis. Treatment was initiated with oral prednisone with a resulting improvement in her liver chemistries (Figure). Discussion: Autoimmune hepatitis in the setting of recent administration COVID 19 vaccine administration has been rarely reported. We present a unique case of COVID vaccine induced autoimmune hepatitis from a non-mRNA based vaccine. It has been suggested that possible mechanisms may include molecular mimicry or bystander activation of dormant autoreactive T-helper cells for both tissue-specific and non-tissue-specific reactions. We aim to shed light to this interesting paradigm and to spark the scientific discourse to further delineate potential mechanisms leading to this uncommon complication.Figure 1.: Liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis.

S3275 A Peculiar Case of Limb-Girdle Muscular Dystrophy Masquerading as Elevated Transaminases

Introduction: A disproportional elevation in aspartate transaminase (AST) and alanine transaminase (ALT) is considered a marker of hepatocellular injury. Guidance on the work up of chronically elevated liver chemistry suggests an algorithmic approach to testing of common causes of liver injury based on the degree of elevation and even mentions consideration of nonhepatic etiologies such as skeletal muscle damage. We present a unique case of asymptomatic elevation in liver chemistries as the herald finding in a patient with limb-girdle muscular dystrophy (LGMD). Case Description/Methods: Our patient is a 19-year-old adopted male who was referred to outpatient gastroenterology clinic for asymptomatic elevation in transaminases. AST was 133 IU/L and ALT was 223 IU/L. Total bilirubin and alkaline phosphatase were normal. He denied alcohol use, prescribed medications, herbal supplements, or weightlifting supplements. BMI was normal. Workup for viral hepatitis, hemochromatosis, autoimmune hepatitis, Wilson’s disease, alpha-1 antitrypsin, celiac disease, and thyroid disease were normal. Liver biopsy revealed reticulin collapse with complete regeneration without inflammation. Subsequent follow-up over years demonstrated persistently elevated but stable elevations. At the age of 24, he began to endorse proximal lower extremity muscle pain and weakness. Creatine kinase (CK) was elevated at 11,937 U/L; aldolase was elevated at 31.4 U/L; myositis workup was normal. Right thigh biopsy revealed a myopathic process. Genetic testing confirmed mutation in the CAPN3 gene consistent with calpainopathy, a subtype of LGMD. Discussion: LGMD is a rare, genetic disorder resulting in loss of ambulation within 20 years after disease onset. Concurrent liver disease is rare in LGMD, but elevations in transaminases can be found because of severe elevations in CK. Our patient was found to have calpainopathy, a subtype associated with a recessive mutation in the CAPN3 gene. Our case demonstrates that beyond the recommended algorithmic evaluation of abnormal liver chemistries, inconclusive evaluation of abnormal liver chemistries in children and young adults should include a CK level to further investigate nonhepatic causes, specifically a myopathic process. Although there is no cure for LGMD, interventions focused on muscle conditioning are more beneficial with early detection to mitigate the devastating effects of this disorder.

S3185 The Great Imitator Spares No Organ: A Case of Syphilitic Hepatitis in an Immunocompetent Patient

Introduction: Syphilis, infamously known as the “great imitator,” is an infectious disease caused by the spirochete Treponema pallidum and can affect many organs. Though uncommon, syphilis can also affect the liver, often manifesting as elevated liver enzymes. Herein we describe the case of a 48-year-old immunocompetent male who was found to have a syphilis-induced acute liver injury. Case Description/Methods: A 48-year-old male presented with a two-week history of dry cough, fever, anorexia, and sore throat. He initially presented to an outside hospital where he was diagnosed with community-acquired pneumonia and discharged on amoxicillin-clavulanate. Given poor improvement in symptoms, he presented to our emergency department several days later and noted additional symptoms of headache, blurry vision, and rash. On admission, liver enzymes were elevated (Table 1), and a mild maculopapular rash was noted on his trunk and extremities. Clinical findings and liver injury were attributed to a drug injury in the setting of recent amoxicillin-clavulanate use. However, the liver injury persisted, prompting additional evaluation. Acute and chronic liver serology tests were unrevealing except for a positive anti-mitochondrial antibody, 44 units, and anti-nuclear antibodies, titers of 1:160. Syphilis screen with rapid plasma reagin was reactive with a titer of 1:32. Given neurological symptoms, a lumbar puncture was performed and revealed a reactive fluorescent treponemal antibody test absorption test. The patient was diagnosed with secondary syphilis complicated by neurosyphilis and syphilitic hepatitis. The patient completed a two-week course of intravenous penicillin with complete resolution in symptoms. After initiation of penicillin, the patient's liver chemistries downtrended and normalized after treatment, confirming the diagnosis of syphilitic hepatitis. Discussion: Syphilitic hepatitis is an uncommon manifestation of syphilis. Suspicion should be raised in patients with elevated liver chemistries, in particular cholestatic pattern, who also have manifestations such as maculopapular rash, low grade fever, arthralgias, headache, and changes in vision. This case highlights the importance of maintaining a broad differential and avoiding anchoring bias when approaching elevated liver chemistries. Table 1. - Liver Function Tests Baseline Outside Hospital Presentation Week 1 Week 3 Alkaline phosphatase (IU/L) 78 1126 1118 997 437 ALT (IU/L) 14 225 231 224 53 AST (IU/L) 19 130 154 139 37 Total bilirubin (mg/dL) 0.8 1.9 4.3 2.0 0.9

S3164 Successful Use of Ribavirin in an Immunocompetent Patient With Severe Hepatitis E

Introduction: Hepatitis E is usually a self-limited disease that does not require antiviral therapy. Limited use of Ribavirin has been described in immunocompromised patients with chronic hepatitis E virus (HEV) infection. We present a rare case of acute hepatitis E in an immunocompetent patient who was successfully treated with Ribavirin, highlighting its potential use in severe cases. Case Description/Methods: A 23-year-old man presented with 5 days of abdominal pain and jaundice 1 month after returning from South Asia. History was negative for liver disease, unprotected sexual activity, or toxic ingestion. Liver chemistries were abnormal with AST 1684, ALT 3001, T bili 6.6, and ALP 188. Initial CBC, BMP, and coagulation studies were at baseline. Abdominal imaging was also unremarkable except for evidence of hepatic parenchymal changes. An extensive viral, toxicological, and autoimmune workup revealed acute HEV infection with a viral load of 1.8 million IU/ml. He was initially managed conservatively but required admission to the liver service by day 4 due to persistently abnormal liver studies and a worsening INR to 1.7. A trial of Ribavirin 200mg BID was initiated and the patient’s transaminases and INR started to downtrend by day 5. By day 6, his symptoms improved and viral load decreased to 23,700 IU/mL. He was discharged on day 8 with a 12-week course of Ribavirin 400mg BID. Liver studies had completely resolved at follow-up 35 days after presentation. Discussion: HEV is a common source of liver failure in regions with high endemicity but is typically self-limited in developed nations. No therapy has been approved for acute hepatitis E, however, ribavirin, a nucleoside inhibitor used for hepatitis C, has been administered effectively in immunocompromised patients with chronic HEV. Limited instances of it being used in healthy patients with acute hepatitis E have also been reported but no clear guidance exists on its use in such rare, severe cases. Although our patient was young and healthy, we chose to trial Ribavirin in light of worsening synthetic liver function and to forestall impending fulminant liver failure. Various regimens have been previously described, ranging from 600-1200mg/day, but we found that a dose of 400-800mg/day was sufficient to induce a 76-fold decrease in viral load within days of Ribavirin initiation. This case provides yet another example of Ribavirin’s effectiveness in the treatment of severe hepatitis E and raises the need for further evaluation for use in such cases.

S1702 Coil-Angitis: A Rare Case of Coil Migration into the Biliary Tree

Introduction: Embolization coils are commonly used to manage hemorrhage after liver injury; however, migration into the biliary tree is uncommon. When this occurs, symptoms of biliary obstruction might develop such as jaundice, cholangitis, stone formation and pancreatitis. Physicians may not be aware of this potential risk, resulting in a delay in diagnosis and an increased morbidity and mortality risk. Herein, we present the case of a patient with history of liver laceration requiring bile duct embolization, and concurrent bile leak, presenting >3 years later with ascending cholangitis. Case Description/Methods: A 27-year-old male with remote history of motor vehicle accident complicated by a liver laceration presented to the ED with one-week onset of right upper quadrant (RUQ) pain, vomiting, and fever. Evaluation at admission was notable for fever of 100.3F, RUQ tenderness, White blood cell count of 13.000/mL. Liver chemistries with bilirubin of 5.0mg/dL, ALT 405U/L, AST 217U/L, ALP 200U/L, consistent with obstructive pattern. Computed tomography showed sequela of liver laceration and bile duct embolization in segment 8, with an unfolded portion of the embolization coil extending inferiorly to the common bile duct, and a dilated bile duct to 15mm (Figure A). The patient was started on antibiotics and underwent urgent ERCP with findings of a coil bundle in the common bile duct with adherent stone and cast material surrounding the coil cast (Figure B). The wire bundle was successfully removed using the extraction balloon and an endoscopic forceps. A significant amount of stone, sludge and pus was also removed from the duct (Figure C). The final cholangiogram demonstrated no further evidence of intraductal embolization coils or other filling defects (Figure D). His pain was relieved, and he was discharged with a common bile duct stent and outpatient follow-up. Discussion: Cholangitis due to biliary coil migration represents an unusual, delayed complication from endovascular embolization. The migrated coil serves as a nidus for stone formation, leading to choledocholithiasis and cholangitis. Our patient was managed successfully with ERCP allowing coil extraction with a favorable outcome. Similar cases of this possible complication have been rarely described in the literature. Our case highlights an uncommon cause of life-threatening cholangitis, warranting a high degree of suspicion and need for detailed documentation of prior interventions.Figure 1.: A. CT showing an unfolded portion of the embolization coil extending inferiorly to the common bile duct. B. Cholangiogram showing a coil bundle in the common bile duct with multiple filling defects suggestive of stones. C. Significant amount of stone, sludge, and coils were removed from the biliary tree. D. Cholangiogram with complete removal of the coil bundle and no further filling defects. The second coil seen in theright upper quartrant were in the liver parenchyma or intra-vascular as confirmed by fluoroscopy.

S2799 Disseminated Cryptococcosis Masquerading as Large Abdominal Mass Concerning for Pancreatic Malignancy in HIV-Positive Patient

Introduction: Gastrointestinal cryptococcus is a rare occurrence in HIV-positive patients. Symptoms may be nonspecific thus the differential for abdominal masses must remain broad. We report a patient with HIV who presented with abdominal pain and watery diarrhea, found to have a large abdominal mass on computed tomography initially thought to be lymphoma or a primary pancreatic tumor. He underwent endoscopic ultrasound-guided (EUS) biopsy of the mass which was consistent with a cryptococcoma. Case Description/Methods: A 55-year-old male presented with severe, diffuse abdominal pain for one week duration associated with profuse watery, non-bloody diarrhea and intermittent chills. Medical history included HIV for 30 years with poor compliance with antiretroviral regimen, recent pneumocystis pneumonia and previous cryptococcal meningitis. Physical exam revealed an ill appearing, cachectic male with abdominal tenderness. Labs revealed a white blood cell count of 18.5 K/uL (ref: 4.0-10.8 K/uL) with 84% neutrophils (ref: 40-75%), sodium of 132 mmol/L (ref: 135-146 mmol/L) and potassium 2.7 mmol/L (ref: 3.5-5.1 mmol/L). His viral load was 109,385 copies/mL (ref: neg copies/mL) and absolute CD4 count was 56 lymphocytes/uL (ref: 330-1520 lymphocytes/uL). Liver chemistries were unremarkable. Stool studies for regional pathogens, ova and parasites, and clostridium difficile were negative. A CT scan of the abdomen and pelvis revealed ill-defined cystic/necrotic upper abdominal lymphadenopathy with mass effect and possible invasion of the adjacent liver (Figure 1A). The pancreas and caudate lobe of the liver were inseparable from the mass which raised concern for primary pancreatic tumor or lymphoma. He underwent EUS-guided biopsy of the peripancreatic mass (Figure 1B) with pathology consistent with a cryptococcoma (Figure 1C, 1D). He was started on amphotericin B and transitioned to high dose fluconazole due to adverse effects. Repeat imaging revealed significant reduction of the mesenteric lymphadenopathy (Figure 1E). He was discharged in stable condition and remained on fluconazole indefinitely. Discussion: Cryptococcal infection remains the second most common cause of acquired immunodeficiency syndrome related mortality after tuberculosis. The most common sites of cryptococcal infection are the lungs, brain, eyes, or central nervous system; abdominal dissemination is rare. Biopsy via EUS can be useful in diagnosis of cryptococcoma. Early identification and treatment of cryptococcal infections can increase survival rates.Figure 1.: A) CT image showing ill-defined cystic/necrotic upper abdominal lymphadenopathy with mass effect and possible invasion of the adjacent liver B) Endoscopic ultrasound imaging showing peripancreatic mass C) Hematoxylin and Eosin cellblock at 40X magnification showing abundant neutrophils and necrotic debris D) Grocott’s Methenamine Silver stain showing fungal yeast with narrow base budding E) Significant reduction of the mesenteric lymphadenopathy after antifungal therapy initiation.