Elevated Liver Function Research Articles

Clinical and Epidemiological Features of Pediatric COVID-19: A Retrospective Study.

There is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID-19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID-19 in Iran. A retrospective study was performed to assess medical records of children with COVID-19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded. In this study, 600 medical records of pediatric COVID-19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID-19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID-19 had substantially higher levels of various inflammatory markers (C-reactive protein (CRP), fibrinogen, and d-dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma-glutamyl transferase (GGT) compared to children with mild COVID-19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID-19 (p < 0.001). In addition, children with severe or moderate COVID-19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID-19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID-19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate-to-severe COVID-19 compared to patients with mild COVID-19 (p < 0.001). The outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID-19 compared to those with mild COVID-19.

Synergistic Effects of Fructose and Food Preservatives on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): From Gut Microbiome Alterations to Hepatic Gene Expression.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of MASLD. Methods: We utilized a human microbiota-associated mouse model, administering 10% fructose with or without preservatives for 11 weeks. Liver histology, hepatic gene expression (microarray analysis), biochemical markers, cytokine profiles, intestinal permeability, and gut microbiome composition (16S rRNA and Internal Transcribed Spacer (ITS) sequencing) were evaluated. Results: Fructose and potassium sorbate synergistically induced liver pathology characterized by increased steatosis, inflammation and fibrosis. These histological changes were associated with elevated liver function markers and altered lipid profiles. The treatments also induced significant changes in both the bacterial and fungal communities and disrupted intestinal barrier function, leading to increased pro-inflammatory responses in the mesenteric lymph nodes. Liver gene expression analysis revealed a wide range of transcriptional changes induced by fructose and modulated by the preservative. Key genes involved in lipid metabolism, oxidative stress, and inflammatory responses were affected. Conclusions: Our findings highlight the complex interactions between dietary components, gut microbiota, and host metabolism in the development of MASLD. The study identifies potential risks associated with the combined consumption of fructose and preservatives, particularly potassium sorbate. Our data reveal new mechanisms that are involved in the development of MASLD and open up a new avenue for the prevention and treatment of MASLD through dietary interventions and the modulation of the microbiome.

Investigating the Relationship Between Demographic and Laboratory Factors with the Incidence of PTE in COVID-19

Background: In 2019, after the first case was discovered in Wuhan, China, the COVID-19 virus began to spread rapidly across the world, leading the WHO to declare the disease a public health emergency. Objectives: Thromboembolism refers to the formation of a clot in a vein, which then travels through the vascular system, potentially blocking blood flow in another location. Methods: This retrospective cohort study aimed to investigate the risk factors for pulmonary embolism in COVID-19 patients hospitalized at Firoozabadi Hospital from May to the end of December 2020. After extracting the required information, the data was entered into SPSS version 26 software for analysis. Results: In total, data from 283 COVID-19 patients admitted to Firouzabadi Hospital in Tehran in 2020 were collected. The average age of the patients was 58.8 ± 15.9 years. Among the 283 patients, 162 (57.6%) were male, 79 patients (27.9%) had pulmonary embolism, 102 patients (36%) were smokers, and 107 patients (37.8%) had a history of hypertension. A significant relationship was observed between the occurrence of pulmonary embolism and elevated levels of, white blood cells (WBC) (P = 0.0001), lactate dehydrogenase (LDH) (P = 0.0001), D-dimer (P = 0.0001), polymorphonuclear neutrophils (PMN) (P = 0.020), lymphocytes (P = 0.013), alkaline phosphatase (Alk.P) (P = 0.025), alanine aminotransferase (ALT) (P = 0.019), and aspartate aminotransferase (AST) (P = 0.017). Conclusions: Based on the results of this study, the incidence of pulmonary embolism in hospitalized COVID-19 patients who underwent CT angiography due to clinical suspicion of thrombosis was 27.9%. Additionally, factors such as smoking, a previous history of pulmonary thromboembolism, high WBC, elevated liver function tests (LFT), and elevated LDH levels were identified as risk factors for the occurrence of pulmonary embolism in these patients.

Seropositivity of hepatitis A and E viruses in patients attending a tertiary care center in central India

Objectives: Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are significant global health concerns that contribute to acute viral hepatitis. This study aimed to investigate the prevalence of HAV, HEV, and co-infections in a tertiary care hospital setting in central India. Materials and Methods: This retrospective observational study analyzed 987 clinical specimens collected from suspected acute viral hepatitis cases over 5 years (2019–2023). Commercially available enzyme-linked immunosorbent assay kits were used to detect HAV and HEV immunoglobulin M antibodies. Statistical analysis: Demographic data and clinical information were collected and analyzed using Chi-square tests. P &lt; 0.05 was considered statistically significant, indicating a significant association between the variables under investigation. Results: Overall, 32.72% of patients were seropositive for either HAV, HEV, or both. The prevalence of HAV was 22.9%, HEV was 9.83%, and co-infection was 3.24%. HAV infection was more prevalent in children (0–14 years), whereas HEV was more prevalent in adults. Both HAV and HEV infections were associated with elevated liver function markers, with the highest levels observed in co-infected cases. The monsoon season had the highest number of cases. Conclusions: This study revealed a substantial burden of HAV, HEV, and co-infections in central India. The observed sex—and age-specific prevalence patterns warrant further investigation. Effective public health strategies addressing sanitation, hygiene practices, and HAV vaccination programs are crucial to reducing the disease burden.

6898 A Case Report Of Drug-Induced Liver Injury Secondary To Sublingual Estradiol In A Transgender Woman

Abstract Disclosure: F. Manas: None. E. Davydov: None. A. Caines: None. K. Estrada: None. J.E. Shill: None. Drug-induced liver injury (DILI), the leading cause of acute liver failure in the United States, occurs in response to a medication or natural compound. Estrogens can lead to idiosyncratic DILI. According to LiverTox [livertox.nih.gov], estrogen has a likelihood score of A (highly likely) to cause DILI, whereas spironolactone has a likelihood score of D (rare). The current formulations of estrogens usually produce a mixed or cholestatic pattern of liver enzyme elevations, however very early, the ALT levels can be markedly elevated (5- to 20-fold). One can be asymptomatic. Often the liver injury resolves after removing the offending agent. We present a case of DILI with elevations of both alanine transferase (ALT) and aspartate transferase (AST), secondary to sublingual estradiol (E2). A 23-year-old transgender female presented for feminizing gender-affirming care. She was started on sublingual E2 2 mg once daily and spironolactone 100 mg orally twice daily. Approximately 14 weeks later, sublingual E2 was increased to 2 mg twice daily for a below-target E2 level, and spironolactone was decreased to 50 mg twice daily due to gas and nausea. Routine blood work three weeks later showed elevated liver function tests (LFTs) in a hepatocellular pattern with ALT of 216 IU/L (normal:&amp;lt;52IU/L), AST of 223 IU/L (normal:&amp;lt;35 IU/L), with normal total bilirubin and alkaline phosphatase. LFTs were normal six months prior. At the time of liver injury, she had consumed six alcoholic beverages in the previous fourteen days, and two doses of acetaminophen. She had no personal history of autoimmunity and no family history of liver disease. Acute hepatitis screen was normal. Abdominal US with liver Doppler was unremarkable. E2 and spironolactone were discontinued. Evaluation by hepatology lead to a diagnosis of DILI from sublingual E2, based on the temporal relationship between initiation of E2 and LFT elevation. Other potential causes of elevated LFTs were excluded. Although she reported alcohol use, the AST/ALT elevation was not in a classic 2:1 pattern. Three weeks after cessation of E2 and spironolactone, her LFTs normalized. Spironolactone was resumed along with E2 by patch, but due to skin-adherence issues she was transitioned to injectable E2 valerate. Her LFTs have remained normal since. This case illustrates a rare but potentially dangerous adverse event of DILI secondary to sublingual E2. Due to the low incidence of liver injury in various studies of individuals with gender incongruence on hormone therapy, current evidence does not support routine liver enzyme monitoring. Clinicians should be aware of the potential risk of liver injury and counsel patients accordingly. As in this case, patients may be successfully rechallenged with the offending DILI medication. Further studies on different formulations of hormone therapy and their effects on the liver would be beneficial in this unique population. Presentation: 6/2/2024

6517 Cardiac Tamponade Secondary to Occult Primary Hypothyroidism

Abstract Disclosure: L. Javed: None. H. Al jumaili: None. A. Mahaldar: None. I. Goyal: None. N. Shakir: None. E. Punni: None. Introduction: The incidence of pericardial effusion in hypothyroidism seems to correlate with severity and duration of the condition and ranges from 3% to 37%. Cardiac tamponade resulting from hypothyroidism is exceptionally rare. We present a case of a patient presenting with this complication.Case Summary:A 38-year-old woman presented during a routine clinic visit with symptoms of fatigue and was found to have elevated liver functions enzymes with ALT 107 (N&amp;lt;48 U/L ) and AST 70 (N&amp;lt;47 U/L)Further evaluation through abdominal imaging revealed incidental finding of a partially imaged moderate pericardial effusion. A subsequent echocardiogram showed circumferential pericardial effusion with early tamponade physiology, necessitating immediate referral to the emergency room (ER) for further assessment and management.Upon admission to the ER, the patient reported progressive fatigue, increased sleep and menorrhagia over 8 months. There were no accompanying symptoms of weight gain or constipation. Family history was positive for thyroid disease in her grandmother. Initial vital signs on admission were Blood pressure: 119/86, Pulse: 55, Respiratory Rate: 13, Temp: 36.7 °C. Electrocardiogram showed sinus bradycardia. Laboratory findings were significant for: Hgb 8.7 (N&amp;gt;11.5), MCV 77.5 (N&amp;gt;80 fL), mildly elevated ALT 56, markedly elevated TSH 255 (N&amp;lt;5 IU/mL), low free T4 &amp;lt;0.1 (N ≥ 0.7 ng/dL), low free T3 &amp;lt;0.6 (N ≥2.0 pg/m), and elevated TPO 472 (N 35 IU/mL). Infectious and rheumatologic work-up were negative. Thyroid ultrasound showed heterogenous echogenicity consistent with thyroiditis.Patient underwent urgent pericardiocentesis draining 750 ml of clear yellowish pericardial fluid. Simultaneously, the patient was initiated on daily levothyroxine at a dose of 112 mcg.Stability in hemodynamics and repeat echocardiogram showcasing no pericardial effusion facilitated the patient’s discharge. Notable improvement with reduction in TSH from 260 to 20 was seen at the one-month follow-up in endocrinology clinic. Conclusion: Hypothyroidism should be considered in patients diagnosed with cardiac tamponade presenting with bradycardia, as in this case. It's been observed that hypothyroidism can affect LFTs which typically resolve with thyroid replacement. Treatment of cardiac tamponade depends on the patient's hemodynamic status. For early mildly affected cases of tamponade, a conservative approach involving close monitoring and limiting fluid intake may suffice, but drainage is often necessary. Since the pericardial effusion and tamponade stem from hypothyroidism, there's a high chance of effusion recurring after drainage. Hence, administering levothyroxine is essential, often leading to effusion resolution within 2-12 months without recurrence. Presentation: 6/3/2024

Pregnancy Management and Outcomes in a Small Bowel, Pancreas, and Liver Transplant Recipient: A Case Report and Literature Review.

BACKGROUND Small bowel transplantation (SBT) is a rare but life-saving surgery. However, successful full-term pregnancies in individuals with SBT are exceedingly rare due to the nutritional and immunosuppression challenges this transplant poses for pregnancy. Therefore, clear guidelines for treating pregnant SBT recipients are unavailable. Here, we report the second case of a successful pregnancy in an individual with a triple organ transplant, including SBT, highlighting the need for careful immunosuppressive management and multidisciplinary care. CASE REPORT A 20-year-old woman in the third trimester of pregnancy with a history of small bowel, liver, and pancreas transplantation at age 1 year presented with elevated liver function test results. She had been taking tacrolimus, sirolimus, and prednisone before pregnancy, with no signs of organ rejection. While sirolimus and prednisone was discontinued upon conception, laboratory test results at presentation revealed low serum tacrolimus levels. The patient had an acute kidney injury and pulmonary edema during her hospitalization and received a diagnosis of preeclampsia. She underwent a successful cesarean delivery, due to labor induction complications; however, about 1 month after hospital discharge, the patient experienced elevated liver enzymes, which was treated with high-dose steroids and adjusted tacrolimus. Sirolimus was restarted, and the patient's liver enzymes have been normalized to date. CONCLUSIONS Comprehensive multidisciplinary care, as well as monitoring and optimizing immunosuppression, are essential for pregnant SBT recipients throughout the prenatal, perinatal, and postpartum periods to mitigate risks, prevent graft rejection, and ensure positive maternal and fetal health outcomes.

Ursodeoxycholic acid in hepatobiliary diseases

Background: This study aimed to summarize evidence of ursodeoxycholic acid (UDCA) use in the management of hepatobiliary diseases, present indications for UDCA use in Korea, and reimbursement criteria for UDCA use in the country.Current Concepts: UDCA is currently approved for the treatment and prevention of gallstone in obese patients with rapid weight loss after post-bariatric surgery, primary biliary cirrhosis (PBC), chronic liver disease with markedly elevated liver function test values, and chronic hepatitis C. However, the approval and reimbursement criteria for UDCA depend on the dose, specific diseases, and circumstances. UDCA is administered at doses of 100, 200, and 300 mg. The 100 mg dose is available over-the-counter, whereas a prescription is required for the 200 and 300 mg doses. The approval standards differed by dose: UDCA 100 mg for biliary diseases and chronic liver disease; UDCA 200 mg for gallstone, PBC, and chronic hepatitis C; and UDCA 300 mg for PBC, gallstone prevention in obese patients, and patients who had undergone gastrectomy. Co-administration of UDCA with antiviral drugs may require patients to bear some costs. UDCA can be combined with either milk thistle or biphenyl dimethyl dicarboxylate but not both.Discussion and Conclusion: UDCA is a relatively safe medication with many benefits. The current reimbursement standards for hepatobiliary diseases include chronic liver disease with elevated liver enzyme levels, gallstone, PBC, chronic hepatitis B, and chronic hepatitis C. Because UDCA is administered at varied doses, it is important to know the appropriate dose and regimen for each condition.

Primary neuroendocrine tumor of the perihilar bile duct: A case report

Neuroendocrine tumors (NETs) arising from extrahepatic bile ducts are very rare. We present a patient with perihilar NET who was operated on with a preoperative diagnosis of Klatskin tumor. A 58-year-old female patient was admitted with abdominal pain and jaundice. Laboratory data showed elevated serum bilirubin levels and liver function tests. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) findings were consistent with perihilar bile duct tumor. The patient was operated on with a diagnosis of Klatskin tumor. She underwent right hepatectomy, resection of the extrahepatic bile duct, portal lymphadenectomy and Roux-en-Y hepaticojejunostomy. The final pathologic examination of the resected specimen demonstrated a well differentiated neuroendocrine tumor (Grade 1). NETs originating from perihilar bile ducts are extremely rare, and preoperative definite diagnosis is very difficult. It should be kept in mind that NET may be one of the rare causes of perihilar bile duct obstruction.

Nontyphoidal Salmonella Hepatitis: A Rare Complication of a Common Enteric Infection

ABSTRACT Hepatitis from nontyphoidal Salmonella gastroenteritis is rare, especially in immunocompetent patients. We present the case of a 30-year-old woman who was found to have Salmonella serotype C2 gastroenteritis and elevated liver function tests concerning for concurrent hepatitis. An extensive workup was negative for other etiologies, making Salmonella the likely culprit. The patient was managed with supportive measures as her liver function tests and symptoms were improving before obtaining microbiological data. Since the role of antibiotic therapy in such cases is not well studied, disease severity in accordance with current guidelines should be used to tailor treatment on a case-by-case basis.

Hepato-renal protective impact of nanocapsulated Petroselinum crispum and Anethum graveolens essential oils added in fermented milk against some food additives via antioxidant and anti-inflammatory effects: In silico and in vivo studies

The study assessed the efficacy of parsley and dill essential oils (EOs) nanocapsules incorporated into fermented milk in hepato-renal protection against specific food additives. A molecular docking assay was conducted between parsley and dill EOs bioactive molecules and inflammatory cytokines. Freeze-dried parsley and dill EOs nanocapsules were developed, characterized for their morphological structure, particle size, zeta potential, polydispersity index and encapsulation efficiency and assessed in fast green dye and sodium benzoate (SB) combination-treated rats. The docking results revealed that the primary constituents of parsley and dill EOs (apiol, myristicin, α-pinene, (−)-carvone, and d-limonene) interacted with the active sites of TNF-α, IL-1β and TGF-1β cytokines with hydrophobic and hydrogen bond interactions. D-limonene had the highest binding affinity (6.4 kcal/mol) for the TNF-α. Apiol and myristicin had the highest binding affinity (5.1, 5.0, 5.0 and 5.0 kcal/mol, respectively) for the IL-1β and TGF-β1 receptors. Biochemically and histopathologically, the excessive co-administration of fast green and SB revealed adverse effects on the liver and the kidney. Whereas the treatment with parsley and dill EOs nanocapsules afford hepato-renal protective effects as manifested by suppression the elevated liver and kidney functions. Parsley and dill EOs nanocapsules showed a significant reduction of the liver (64.08 and 80.5 pg/g, respectively) and kidney (59.3 and 83.6 pg/g, respectively) ROS. Moreover, parsley and dill EOs nanocapsules down-regulated the liver and the kidney inflammatory cytokines (IL-6, TNF-α, IL-1β and TGF-1β) and lipid peroxidation and up-regulated the antioxidant enzymes. In conclusion, the data suggest a potential hepato-renal protective effects of parsley and dill EOs nanocapsules.

Hepatoprotective effect of Solanum anomalum leaf on doxorubicin-induced hepatotoxicity in male rats

Background and aims: Solanum anomalum Thonn. ex Schumach (Solanaceae) parts are used locally in ethnomedicine to treat various diseases. This work investigated the hepatoprotective potential of the S. anomalum to validate its ethnomedicinal uses and give scientific proof to its claimed antidotal activity in folkloric medicine. Methods: The hepatoprotective activity of S. anomalum leaf extract (70-210 mg/kg) was investigated against doxorubicin (DOX)-induced liver injury in rats. Rats were divided into five groups of six rats each and treated concomitantly with DOX (2.5 mg/kg i.p) and leaf extract (70, 140, and 210 mg/kg orally) for 14 days. Vitamin C was used as a standard drug. Liver function indices, liver enzymatic and nonenzymatic antioxidants, malondialdehyde (MDA) level, and histological assessment of the liver were determined to assess the hepatoprotective potentials of the extract. Results: DOX elevated liver function indices (AST, ALT, ALP, total and direct bilirubin) significantly (P&lt;0.05). These parameters were markedly reduced by coadministration of the leaf extract (70-210 mg/kg) (P&lt;0.05-0.01) when compared to the DOX-only group. Also, the extract coadministration improved total protein and albumin levels, which were reduced by DOX. Moreso, levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) that were decreased by DOX were significantly (P&lt;0.01) elevated by the leaf extract. In contrast, the raised MDA level was reduced. The DOX-only group had severe pathological features in its histological liver section, which were comparably reduced in the extract-treated groups. The histopathological changes corroborate other biochemical parameters determined, thus indicating hepatoprotective solid activity. Conclusion: This study’s findings suggest that the leaf extract of S. anomalum possesses liver protective potentials, which may be due to the antioxidant activities of its phytochemical constituents. This property can be exploited in the treatment of DOX-related toxicities.

Results of the Simultaneous Combination of Ponatinib and Blinatumomab in Philadelphia Chromosome-Positive ALL.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate by reverse transcriptase-polymerase chain reaction was 83% (67% at the end of course one), and the rate of measurable residual disease negativity by next-generation clono-sequencing was 98% (45% at the end of course one). Only two patients underwent hematopoietic stem cell transplantation (HSCT). Seven patients relapsed: two with systemic disease, four with isolated CNS relapse, and one with extramedullary Ph-negative, CRLF2-positive pre-B ALL. The estimated 3-year overall survival rate was 91% and event-free survival rate was 77%. Three patients discontinued blinatumomab because of adverse events (related, n = 1; unrelated, n = 2) and nine discontinued ponatinib because of cerebrovascular ischemia, coronary artery stenosis, persistent rash, elevated liver function tests with drug-induced fatty liver, atrial thrombus, severe arterial occlusive disease of lower extremities, pleuro-pericardial effusion, and debilitation. In conclusion, the simultaneous combination of ponatinib and blinatumomab is a highly effective and relatively safe nonchemotherapy regimen. This regimen also reduces the need for intensive chemotherapy and HSCT in first remission in the majority of patients.

Case report: Conservative management of a blunt trauma to a horseshoe kidney

With trauma representing the leading cause of death in children, and renal injuries representing a large proportion of that trauma, understanding the appropriate management of renal injuries is vital to preventing pediatric morbidity and mortality. Cases involving aberrant anatomy are even more crucial to understand as there is less data on appropriate management. Here, a case is presented of a 7-year-old male presenting after a horse kick to the abdomen resulting in traumatic disruption of a previously unknown horseshoe kidney and the subsequent conservative management. The patient presented with abdominal pain, leukocytosis, and elevated liver function enzymes. An abdominal and pelvic Computed Tomography (CT) demonstrated a horseshoe kidney with a grade IV laceration to the isthmus and left lower pole of the kidney resulting in fracture/disruption of previously fused horseshoe kidneys. Additionally, there was a large retroperitoneal hematoma and hemoperitoneum. The patient was successfully managed with observation, and hemodynamic monitoring and has had resolution of hematoma and preserved kidney function through 8 months of follow-up. In conclusion, this is an example of how a patient with complicated renal anatomy can be managed conservatively to model for potential future cases.

Acute Presentation of Autoimmune Hepatitis: Case Report

This case report describes the clinical presentation, diagnostic evaluation, and treatment outcome of a 38-year-old female patient presenting with yellow discoloration of eyes and urine, along with associated symptoms such as nausea, poor appetite, abdominal pain, extreme fatigue, and mild joint pain. The patient had a history of amenorrhea for three months and no family history of autoimmune disease or drug-induced liver injury. Upon examination, the patient exhibited deep icterus and mild tender hepatomegaly, but without signs of acute liver failure. Laboratory investigations revealed elevated liver function markers and positive autoimmune antibodies, including antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA), while ruling out other possible etiologies such as viral hepatitis, Wilson's disease, and hemochromatosis. Imaging studies showed features of acute hepatitis, and liver biopsy could not be performed due to prolonged prothrombin time. The patient was diagnosed with probable autoimmune hepatitis (AIH) and initiated on a treatment regimen consisting of prednisolone 40 mg daily, which was gradually tapered over time and added azathioprine 100 mg daily. The patient demonstrated significant improvement in liver function tests with this treatment approach. However, she discontinued treatment on her own accord but continued to have normal liver function during subsequent follow-up visits. During the consultation, the patient and healthcare provider engaged in a comprehensive discussion concerning the significance of sustained treatment over an extended period and the inherent possibility of relapse.

Efficacy and toxicity of BRAF targeted therapy in elderly patients with melanoma.

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients &gt; 65). The use of BRAF &amp; MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients &gt; 65. Methods: We identified electronic medical records of all melanoma patients &gt; 65 that were treated with BRAF &amp; MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second &amp; third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF &amp; MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment

ContextKlinefelter syndrome (KS) is associated with hypergonadotropic hypogonadism, which contributes to characteristic phenotypical manifestations including metabolic alterations. Extensive research has demonstrated important associations between androgens and liver function.ObjectivesInvestigation of the association between metabolic parameters, sex hormones and liver function in males with KS, both treated (T-KS) and untreated (U-KS) and healthy control males.MethodsA total of 65 KS males were recruited, of which 32 received testosterone replacement therapy (TRT). Also, 69 healthy controls were recruited. We used alanine aminotransferase (ALAT), alkaline phosphatase and PP (prothrombin-proconvertin time ratio) as the main liver markers. Multivariable regression was performed within the three groups. All statistics were calculated using STATA. Principal component analysis was utilized to demonstrate the interconnected patterns among all measured biomarkers, and to elucidate how the different groups were linked to these patterns.ResultsHigher levels of main liver markers were observed in U-KS compared to controls, with no significant differences between U-KS and T-KS. T-KS had lower abdominal fat, total cholesterol, and LDL cholesterol than U-KS. Using multivariable models, variation in ALAT in U-KS was explained by HOMA2%S; in T-KS by BMI and SHBG; and in controls by hip circumference and estradiol. We found no multivariable models explaining variation in PP in U-KS; in T-KS, PP was explained by BMI and LDL cholesterol, and in controls by total cholesterol. Using principal component analysis U-KS was positively associated to D1 (an obese profile, which also included ALAT) and controls negatively associated with D1 (non-obese profile).ConclusionKS males have mild liver dysfunction reflected by a significant increase in the main liver markers and decrease in albumin. The presented data underscore a primary role of metabolic conditions including obesity, insulin resistance and unfavourable lipid profile, in the elevated liver function markers seen in males with KS. Whether TRT can improve liver function in KS warrants further studies. Our findings, highlight that an evaluation of the liver function should be part of the clinical care in males with KS.

A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L.: Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L. (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. Chelidonium majus L., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

Vincamine alleviates intrahepatic cholestasis in rats through modulation of NF-kB/PDGF/klf6/PPARγ and PI3K/Akt pathways

The defect in the hepatobiliary transport system results in an impairment of bile flow, leading to accumulation of toxic compounds with subsequent liver disorders. Vincamine, a plant indole alkaloid that is utilized as a dietary supplement, has been known for its promising pharmacological activities. For the first time, the present study was planned to estimate, at the molecular level, the potentiality of vincamine against alfa-naphthyl isothiocyanate (ANIT)-induced hepatic cholestasis. Liver function tests were analyzed. Hepatic activity of SOD and levels of GSH and MDA were assessed. Hepatic contents of bax, bcl2, NF-kB, PPARγ, catalase, heme-oxygenase-1, NTCP, and BSEP were evaluated using ELISA. mRNA levels of NF-kB, IL-1β, IL-6, TNFα, PDGF, klf6, PPARγ, and P53 were examined using qRT-PCR. PI3K, Akt and cleaved caspase-3 proteins were assessed using western blotting. Histopathological analyses were performed using hematoxylin & eosin staining. ANIT-induced hepatic cholestasis elevated liver function tests, including AST, ALT, GGT, ALP, and total bilirubin. ANIT reduced the protein expression of NTCP and BSEP hepatic transporters. It induced the expression of the inflammatory genes, TNFα, IL-6, IL-1β, and PDGF, and the expression of NF-kB at the genetic and protein level and suppressed the anti-inflammatory genes, klf6 and PPARγ. Also, antioxidant markers were reduced during ANIT induction such as GSH, SOD, catalase, heme-oxygenase-1 and PI3K/Akt pathway, while MDA levels were elevated. Furthermore, the expression of P53 gene, bax and cleaved caspase 3 proteins were activated, while bcl2 was inhibited. Also, the histopathological analysis showed degeneration of hepatocytes and inflammatory cellular infiltrates. However, vincamine treatment modulated all these markers. It improved liver function tests. It inhibited the expression of NF-kB, TNFα, IL-6, IL-1β and PDGF and activated the expression of klf6 and PPARγ. Furthermore, vincamine reduced MDA levels and induced GSH, SOD, catalase, heme-oxygenase-1 and PI3K/Akt pathway. Additionally, it inhibited expression of P53 gene, bax and cleaved caspase 3 proteins. More interestingly, vincamine showed better outcomes on the hepatic histopathological analysis and improved the alterations induced by ANIT. Vincamine alleviated hepatic dysfunction during ANIT-induced intrahepatic cholestasis through its anti-inflammatory and antioxidant efficacies by the modulation of NF-kB/PDGF/klf6/PPARγ and PI3K/Akt pathways.

HEART FAILURE WITH RELAPSING ATRIAL FIBRILLATION: BELOW THE SURFACE

Abstract Advances in pharmacologic and device therapy have greatly improved prognosis of patients with HFrEF. However, the typical clinical course is still characterized by recurring symptoms, worsening functional status and risk of frequent hospitalizations. A 72–years–old male patient with arterial hypertension, poorly controlled T2DM, TIA and chronic kidney disease presented to Cardiology service in 2018 with dyspnoea on effort and first evidence of EF 35% at echocardiography. He was admitted for elective coronary angiography, which demonstrated limited coronary heart disease of circumflex artery and its first marginal branch, treated by PTCA and stenting. CMR confirmed severe LV dysfunction, but also revealed extensive fibrotic areas with ischaemic and non–ischaemic patterns beyond revascularized regions. With such evidences, HF treatments were intensified, with titration of disease– modifying therapies and DOAC was added for asymptomatic paroxysmal AF. CRT–D was implanted for QRS of 160 msec, which was narrowed to 130 msec. Nevertheless, in one–year time the patient presented worsening of symptoms with several hospital admissions for acute HF and AF with fast rate. A switch to rhythm–control strategy was hence chosen. DCCV was performed, after an initial deferral for thrombosis of LAA due to poor adherence to DOAC. However, three–days after DCCV, the patient presented again to emergency services for dyspnoea, left upper flank pain and AF with fast rate. He was admitted to Acute Medicine Unit and treated with high flow O2, iv Furosemide and Digoxin, analgesics. CT chest and abdomen with contrast was performed in the suspicion of systemic venous thromboembolism for persistent type 1 respiratory failure, raised D–dimer and elevated liver function tests, despite appropriate anticoagulation. CT revealed an unexpected left superior pulmonary vein thrombosis, splenic and small left renal infarcts. The patient was discharged after recovery on subcutaneous heparin. At 15–day review, the patient was in stable conditions and awaiting completion of coagulation screening tests. This case study addresses some important aspects in the care of HF. An accurate assessment of HF aetiology and recurrent triggers, a timely planning of pharmacologic and device treatments, alongside with management of co–morbidities, therapeutic adherence and appropriate anticoagulation, can provide the clinician powerful tools to accomplish the difficult task of managing HF below the surface.