Increased Liver Function Tests Research Articles

Case Report: Managing the Coinfection of Cerebral Malaria and Dengue in the Intensive Care Unit

Background: Dengue and malaria are the two most common arthropod-borne illnesses, but cases of multiple infections are extremely uncommon. The mortality rate for individuals with dengue and malaria was higher than the death rate for those with malaria alone.Case: An intubated 53-year-old male was referred from a class B hospital because of severe malaria with suspected cerebral malaria, dengue fever (day-11), septic shock and acute kidney injury. His initial laboratory investigation showed increasing pattern of WBC, thrombocyte, anemia, peripheral blood smear normochromic normocytic erythrocyte, poikilocytosis (ovalocytes (+), teardrop cells (+)), normoblasts (+), presence of Plasmodium malariae trophozoite and schizont stage parasites, positive result of IgM and IgG anti dengue, increased liver function test, increased BUN and creatinine serum levels, hyperbilirubinemia, hypoalbuminemia, and normal result of blood gas analysis. On the sixth day of ICU admission, the patient gradually regained consciousness with appropriate responsiveness and showed clinical improvement. The patient was discharged after one month of hospital care with the last peripheral blood smear showing no parasites detected.Discussion: Mono-infection with malaria and dengue, two mosquito-borne diseases endemic to tropical and subtropical regions, often carries a high risk of fatality. The risk becomes even more pronounced when co-infection occurs. The early diagnosis and management in the ICU are crucial for cases of coinfection involving cerebral malaria and dengue. The primary focus is on both definitive and supportive therapies.Conclusion: The prognosis for coinfection of cerebral malaria and dengue is generally poor, but in this case, the patient showed improvement and was able to be discharged without any sequelae.

Four-Year Follow-up of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia Α

Introduction: Hemophilia A is an X-linked ( F8 gene) recessive disorder of hemostasis that results in insufficient factor VIII (FVIII) activity. Adeno-associated virus (AAV)-based gene therapy enables delivery of a modified F8 cDNA, allowing synthesis of functional endogenous FVIII, which prevents bleeding events. We present updated results with nearly 4 years of follow-up on an ongoing gene therapy study in participants with severe hemophilia A (FVIII activity <1%). Methods:The phase 1/2 Alta study (NCT03061201) is a dose-ranging study of giroctocogene fitelparvovec (PF-07055480, previously called SB-525), a recombinant AAV serotype 6 vector encoding a modified B-domain-deleted F8 coding sequence. Four ascending doses of giroctocogene fitelparvovec (9e11, 2e12, 1e13, and 3e13 vg/kg) were infused into adults aged ≥18 years with severe hemophilia A across 4 cohorts (n=2 each). The high-dose (3e13 vg/kg) cohort was expanded to 5 participants. Key endpoints included safety, circulating FVIII activity, use of FVIII replacement therapy, and frequency of bleeding events. Results: Eleven male participants were enrolled in the study (mean [SD] age, 30.3 [7.8] years; White, 81.8%). As of the cutoff date (May 19, 2023), participants had been followed for 153 to 290 weeks. Two participants left the study after Week 156. Of the remaining, 1 participant had not yet completed 4 years (208 weeks). The most common treatment-related adverse events (AEs) reported in the high-dose cohort (n=5) were elevated liver enzymes and infusion-related reactions: increased alanine aminotransferase (ALT; n=3 [60.0%]), increased aspartate aminotransferase (AST; n=2 [40.0%]), pyrexia (n=3 [60.0%]), and tachycardia (n=2 [40.0%]). Treatment-related serious AEs were reported in 1 participant in the high-dose cohort who experienced hypotension and fever, with onset ≈6 h after infusion; the events fully resolved with treatment. AEs (all causality) of ALT increases requiring ≥7 days of corticosteroids were observed in 4 of 5 participants in the high-dose cohort. ALT elevations were managed with tapering courses of corticosteroids (median duration: 56 days; range: 7-135 days), with maintenance of efficacious levels of FVIII activity. Participants in the high-dose cohort have not required steroids since Week 65, have had ALT values in the normal range (follow-up: 156-208 weeks) and normal findings via liver MRI (follow-up: 104-208 weeks). No participant developed a confirmed inhibitor to FVIII. No thrombotic events or liver masses have been detected. Of the 5 participants in the high-dose cohort, 2 had data available through Week 208 and FVIII activity was maintained in the mild to normal range ( Table), consistent with Week 156 results. Of those without Week 208 data, 2 had data through Week 182. One participant maintained FVIII activity in the mild range (14.1% and 24.1% of normal, measured with a chromogenic and 1-stage assay, respectively); the other had FVIII activity of 3.1% and 7.2%. The remaining participant left the study after Week 156, with FVIII activity maintained in the mild range (11.8% and 22.9%). In the high-dose cohort, the mean annualized total bleeding rate [(number of all bleeding episodes starting 3 weeks after study drug infusion) / (observation period in years)] was 0 for the first year post infusion and 1.2 (SD 2.58) throughout the total duration of follow-up. In this cohort, the participant with the lowest FVIII activity level experienced a total of 22 bleeds, with 21 necessitating treatment (8 traumatic; 7 spontaneous; 6 unknown). The other 4 participants had no or very minimal bleeds, including 1 who experienced a bleed in a target joint. No participants in the high-dose cohort have resumed prophylaxis. Conclusion:A single infusion of giroctocogene fitelparvovec gene therapy in participants with severe hemophilia A remains generally well tolerated over a period of nearly 4 years post infusion, with associated increases in FVIII levels in the moderate to normal range, without sustained AEs and with no AEs associated with increased liver function tests since Week 59. The ongoing phase 3 study (NCT04370054) in a larger cohort will provide more long-term data on the safety and durability of giroctocogene fitelparvovec in participants with moderately severe to severe hemophilia A.

CTIM-22. PHASE I STUDY RESULTS OF THE ANTIBODY-CYTOKINE FUSION PROTEIN L19TNF IN COMBINATION WITH LOMUSTINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA REVEAL PROMISING SAFETY AND DURABLE TUMOR RESPONSES

Abstract Treatment options for recurrent glioblastoma are limited and there is a need for novel effective therapies. Recently, we showed synergistic preclinical anti-tumor activity of the immunocytokine L19TNF in combination with lomustine in orthotopic immunocompetent glioma mouse models. L19TNF is an antibody-cytokine fusion protein, comprising the pro-inflammatory cytokine tumor necrosis factor (TNF) fused to the antibody L19 that binds to a tumor-specific epitope of the extracellular matrix protein fibronectin. This allows a targeted delivery of therapeutically relevant doses of TNF to the tumor site through intravenous administration while sparing healthy tissues. Here, we present results of the completed phase I part of a phase I/II open label, multicenter, randomized study to investigate L19TNF in combination with lomustine for patients with recurrent glioblastoma (NCT04573192). Fifteen patients were enrolled from February 2021 – January 2023 and treated at three different dose levels of L19TNF in combination with lomustine. Overall, the treatment was well tolerated. The most common adverse events were asymptomatic increase of liver function tests and a decrease of white blood cells and platelets. Serial MRI assessments revealed near-complete responses in 3 patients (20%) and stable disease in 8 (53%) patients. The median progression-free survival was 4.2 months, progression-free survival rate at 6 months was 46% (7/15 patients), and median overall survival has not been reached after a median follow-up of 11 months. Serial blood assessments demonstrated a treatment-associated increase in C-reactive protein, a peripheral marker for inflammation, which correlated with progression-free survival. A patient, who showed a near-complete response that lasted 12 months relapsed at a different location. Subsequent re-challenge with L19TNF and lomustine again led to a partial response. These encouraging results justify further investigations within the phase II part of the clinical trial that is recruiting patients in four countries.

Experience with carnitine palmitoyltransferase II deficiency: diagnostic challenges in the myopathic form.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form ofCPT II deficiency at Ege University Hospital. A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. Ten patients were examined for rhabdomyolysis ofunknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C>T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C>T (p.Ser113Leu). Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.

Anti-inflammatory and anti-arthritic potential of methotrexate in combination with BA-25, an amino analogue of β-boswellic acid in the treatment of rheumatoid arthritis

β- boswellic acid, a pentacyclic triterpene derived from Boswellia serrata is extensively known for its anti-inflammatory potential. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) is an amino analogue of β-boswellic acid that has shown anti-inflammatory potential in LPS-induced macrophages and animal models. The present study aims at investigation of the combination of BA-25 with the conventional gold standard DMARD methotrexate (MTX) for its anti-inflammatory and anti-arthritic potential using in vitro and in vivo experimental models. The anti-inflammatory potential of MTX versus the combination (BA-25 + MTX) was investigated for inhibition of NO, ROS and pro-inflammatory cytokines including TNF-α and IL-6 using ELISA in LPS-stimulated RAW-264.7 cells. The results demonstrated significant reduction in NO, ROS, TNF- α and IL-6 production with the combination treatment in comparison to MTX alone. The cytokine inhibition potential of the combination was further validated in-vivo using balb/c wherein the combination restored LPS-induced increase in pro-inflammatory cytokines. The toxicological aspect of the in vivo doses of the combination was also investigated in mice after dosing for 28 days wherein the results suggested no significant change in the hematological parameters and serum biochemical parameters in the combination versus the vehicle group. The effect of BA-25 was also investigated on MTX-induced increase in liver function tests and the expression of Bax and blc2. The results demonstrated decrease in the production of liver enzymes with BA-25 administration along with downregulating the expression of apoptotic protein Bax while increasing the expression of anti-apoptotic protein Bcl2. Furthermore, pharmacokinetic studies of BA-25 were conducted in Balb/c mice wherein the compound showed rapid absorption, high volume of distribution and a t1/2 of 13.08. Finally the anti-arthritic effect of the combination of MTX + BA-25 vs MTX alone was investigated using CIA model in DBA/1 mice wherein the treatment with the combination resulted in significant reduction in paw inflammation, IL-6 and IL-1β levels. Furthermore, the western blot analysis demonstrated considerable decrease in the expression of p-NF-κB p65 and p-IκB in the ankle-joint tissue of the CIA mice treated with the combination therapy. The results insinuated increased anti-inflammatory and anti-arthritic potential of the combination of MTX with BA-25 as evident from in to vitro and in-vivo studies.

Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea.

Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of coronavirus disease 2019 (COVID-19) in South Korea in 2021. The Ministry of Food and Drug Safety in South Korea mandate that new medications be re-examined for safety and effectiveness post-approval in at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate the safety and effectiveness of regdanvimab in real-world clinical care. This prospective, multicentre, phase 4 PMS study was conducted between February 2021 and March 2022 in South Korea. Eligible patients were aged ≥ 18years with confirmed mild COVID-19 at high risk of disease progression or moderate COVID-19. Patients were hospitalised and treated with regdanvimab (40mg/kg, day 1) and then monitored until discharge, with a follow-up call on day 28. Adverse events (AEs) were documented, and the COVID-19 disease progression rate was used to measure effectiveness. Of the 3123 patients with COVID-19 infection identified, 3036 were eligible for inclusion. Approximately 80% and 5% of the eligible patients were diagnosed with COVID-19 during the delta- and omicron-dominant periods, respectively. Median (range) age was 57 (18-95) years, and 50.6% of patients were male. COVID-19 severity was assessed before treatment, and high-risk mild and moderate COVID-19 was diagnosed in 1030 (33.9%) and 2006 (66.1%) patients, respectively. AEs and adverse drug reactions (ADRs) were experienced by 684 (22.5%) and 363 (12.0%) patients, respectively. The most common ADR was increased liver function test (n = 62, 2.0%). Nine (0.3%) patients discontinued regdanvimab due to ADRs. Overall, 378 (12.5%) patients experienced disease progression after regdanvimab infusion, with extended hospitalisation/re-admission (n = 300, 9.9%) as the most common reason. Supplemental oxygen was required by 282 (9.3%) patients. Ten (0.3%) patients required intensive care monitoring and 3 (0.1%) died due to COVID-19. This large-scale PMS study demonstrated that regdanvimab was effective against COVID-19 progression and had an acceptable safety profile when used in real-world clinical practice.

Olanzapine for Non-Chemotherapy Related Nausea and Emesis in Patients with a Palliative Care Consult.

Current palliative care guidelines lack a specific treatment algorithm for nausea and emesis. Olanzapine is an atypical antipsychotic with antiemetic activity that's recommended in the guidelines for the treatment of chemotherapy induced nausea and vomiting, but outside of oncologic indications there is a lack of research. To describe the safety and efficacy of olanzapine for nausea and emesis in the palliative care domain, excluding patients actively undergoing chemotherapy or radiation. This retrospective chart review encompassed hospitalized adult patients from six hospitals across a large health system admitted from August 2020 through August 2021, with a palliative care consult, and being treated with olanzapine for nausea or emesis. Data was collected on antiemetic therapy affordability, the ability for patients to tolerate medications by mouth, and safety outcomes such as QTc prolongation and increased liver function tests. A total of 78 patients were included in the study. Olanzapine decreased the number of doses required of antiemetic medications, the median doses of antiemetic medications pre-olanzapine was 1.6 (IQR 0.8-2.8) and post-olanzapine was 0.6 (IQR 0-2.4) (P=0.0006). After olanzapine was initiated, appetite was improved (P < 0.001), cost of antiemetic therapy was reduced by 65 cents per day (P=0.059) and olanzapine was prescribed at discharge in 69% of patients. QTc prolongation was observed in 19% of patients, and increased ALT and AST were observed in 4.3% and 0%, respectively. This retrospective review demonstrated benefit to utilizing olanzapine for nausea and emesis in palliative care patients and should be considered to aid in symptom management.

Duloxetine and Hepatic Injury: A Case Presentation

Duloxetine is a selective serotoninnorepinephrine reuptake inhibitor (SNRI) antidepressant frequently used to treat different psychiatric conditions and neuropathic pain. Increasing reports of hepatic injury have been documented with this medication since its release, in individuals with and without known risk factors for hepatotoxicity. In this case report, we present a 47-year-old female with a documented history of liver injury who developed increase in liver function tests twice, in a dose-dependent occurrence related to this medication. [ Psychiatr Ann . 2023;53(1):47–51.]

Acute pancreatitis complicated by hemolytic uremic syndrome: a pediatric case

BackgroundHemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. The acute pancreatitis-associated HUS is a rare entity, and this case is one of the few pediatric cases reported.Case presentationA 17-year-old girl referred to the emergency department with complaints of abdominal pain, fever, and vomiting. The skin and sclera were icteric. Murphy’s sign was positive. Hemogram was normal, biochemical analysis revealed an increase in liver function tests and cholestasis enzymes. Abdominal CT revealed multiple stones in the hydropic gallbladder lumen and the pancreas was edematous. With a diagnosis of acute pancreatitis supportive treatment was started. Acute kidney failure, cholestasis, anemia, and thrombocytopenia developed at the 2nd day of follow-up. Thrombotic thrombocytopenic purpura was excluded with normal ADAMTS-13 level. Intermittent hemodialysis and plasma exchange (PE) treatments were initiated, considering pancreatitis-related HUS. On the 3rd day of PE, the patient’s urine output exceeded 1 cc/kg per hour. No schistocyte was found in the peripheral smear after 7 PE and 5 hemodialysis sessions. Anemia, thrombocytopenia, and kidney functions improved. On the 15th day of the follow-up, endoscopic retrograde cholangiopancreatography performed, and gallbladder stones were removed.ConclusionThe pathogenesis of HUS developing after acute pancreatitis is not fully understood. The mechanism proposed is that acute pancreatitis triggers cytokine release, resulting in endothelial damage and HUS. In conclusion, HUS may rarely develop in patients with acute pancreatitis. With the early diagnosis and appropriate treatment, the kidney functions can be completely normalized.

Phantom Tumors in COVID-19: A Case Report

Introduction: A phantom tumor, or vanishing lung pseudotumor, is an atypical type of pleural effusion in which there is an accumulation of fluid in the pleural cavity. It is a transient and well-demarcated accumulation of pleural fluid in the interlobar pulmonary fissures and is generally associated with congestive heart failure, hypoalbuminemia, renal failure, hepatic failure, pneumonia, and tuberculosis or pleuritis. In Coronavirus disease 2019 (COVID-19), pleural effusions are also considered uncommon, and they could reflect a more severe state of the condition. The correct diagnosis is important to prevent unnecessary and potentially harmful investigation and treatment. In this study, we reported a rare case of a pleural effusion appearing as a phantom tumor in COVID-19 without congestive heart failure. Case: A 29-year-old man was presented with complaints of dry cough, sore throat accompanied by fever, and fatigue. He denied shortness of breath and loss of taste and smell. He had no smoking habit and did not have any past medical history. Physical examinations were within normal limits, except for a slight fever. The laboratory examination showed positive SARS-CoV-2 RT-PCR and an increased liver function test. His chest X-ray revealed findings suggestive of a phantom tumor accompanied by bilateral pneumonia. The patient received COVID-19 treatments. A follow-up chest X-ray revealed the complete resolution of the lesion. Conclusion: A phantom tumor is a rare case. It is not only caused by heart disease but also by other causes, one of which is COVID-19. The treatment for this condition is based on the underlying disease.

Clinical Features and Outcomes of Gallbladder Polyps in Children.

Background:Gallbladder polyps are rare lesions protruding into the gallbladder lumen with variable clinical presentation. No standard treatment algorithm has been developed for pediatric gallbladders, and the malignant potential of the gallbladder is not clear in children. Therefore, a retrospective study was performed to evaluate the clinical features and treatment options of gallbladder polyps in children.Methods:Between 2014 and 2020, children diagnosed with gallbladder polyps were evaluated for age, gender, clinical features, results of follow-up with ultrasound findings, and treatment options retrospectively.Results:The records of 15 patients with a mean age of 13.2 years (2-20 years) were included. The male: female ratio was 7 : 8. Gallbladder polyps was detected incidentally in 73.3% (n = 11) of the patients. Four (20%) of the patients were symptomatic (26.7%) and complained about abdominal pain. Laboratory tests were normal except in 3 patients who showed slightly increased liver function tests. Two of the patients had 3 polyps on admission. The polyps were 2-10 mm in size. The size of the polyp increased in 5 patients (33.3%) and disappeared in 4 patients (26.6%) in follow-up ultrasound examinations. Five of the patients underwent cholecystectomy and 1 of them was scheduled for surgery. Five of the asymptomatic patients who have polyps less than 10 mm in size are still on follow-up. In patients with cholecystectomy, the histopathology of gallbladders revealed cholesterol polyps (n = 2) and hyperplastic polyps (n = 2). One of the patients with cholecystectomy showed no polyps in histopathological evaluation.Conclusion: Despite the lack of a standardized algorithm, our data suggested that multiple polyps, polyps with increased in size or greater than 10 mm, and the presence of symptoms might require cholecystectomy in children. Asymptomatic patients with small-sized polyps can be identified using ultrasound, and the polyps may disappear during the subsequent follow-up.

Seizures as a Manifestation of Isoniazid Intoxication: A Case Report

Introduction: Isoniazid (INH) intoxication is a serious health problem that can be life-threatening. Acute intoxication manifests as neurological symptoms such as seizures. Case Illustration: A woman, 27 years old, came to the emergency department with seizures after taking ten tablets (3000 milligrams) of Isoniazid. Laboratory examination showed a severe metabolic acidosis and increased liver function test. The management primarily consists of basic life support, antiseizure, and antidote. Conclusion: Isoniazid toxicity is associated with a high mortality rate. The first signs and symptoms of isoniazid toxicity may appear within 30 minutes to two hours. Acute toxicity of Isoniazid may manifest as neurological symptoms such as seizures. Management of INH intoxication consists of controlling the life-threatening condition, administering an antidote such as pyridoxine, and symptomatic supportive therapy. Keywords: Isoniazid, intoxication, seizures

Hepatobiliary System Effects And Clinical Features of Sars-Cov-2 Infection; Case-Control Study

Introduction: Pandemic caused by SARS-CoV-2 infection has been an important health problem worldwide for the last 3 years. The pathogenesis and consequences of liver injury developed in COVID-19 disease are still unclear. We investigated the prevalence of liver function tests (LFTs) abnormalities in COVID-19 patients, their relationship with drugs, the difference between severe and non-severe COVID-19 patients, and the results of the course of LFTs among patients hospitalized in intensive care units and clinics. Methods: 389 patients who applied to Eskişehir City Hospital between March 2020 and October 2020 were included in the study. Demographic data of RT-PCR (+) patients and RT-PCR (-) control groups (age, gender, comorbidities, symptoms), laboratory parameters, radiological examinations, follow-ups in the clinics and intensive care units, drugs used for the infection were collected retrospectively. All patients with COVID-19 were classified as severe cases or mild to moderate cases groups. Results: Abnormal LFTs were found in 115 (35.2%) of 321 patients with RT-PCR(+), and in 10 (14.7%) of 68 patients in the PCR(-) control group. LFTs at the time of hospitalization were 10.3%, 22.7%, 4.9%, 11.4% and 1.2% in the patient group, respectively; in the control group, it was 1.9%, 2.9%, 2%, 3.3%, 0.8% (p=0.610, p=0.00, p=0.269, p=0.198, p=0.158). There was a significant increase in LFTs in patients who received antibiotics (Levofloxacin, Ceftriaxone, Clarithromycin, Tazobactam, Carbapenem), low molecular weight heparins and antiviral (favipravir) treatments (p=0.001, p=0.001, p=0.001). While the increase in LFTs were significant in the mild (40.2%; 8.2%) and severe groups (41.2%; 5.2%), the number of patients with elevated LFTs in the control group was low (0.5%). Conclusion: Liver damage is common in SARS-CoV-2 infection, but it is quite mild. Patients with severe COVID-19 have a higher frequency of abnormal LFTs than those with mild disease. Disease severity, pre-existing liver disease, and advanced age are risk factors for liver damage. Drug-induced liver injury, systemic inflammatory response syndrome, and hypoxia-induced liver injury may be the main etiological factors for liver injury in COVID-19.

Treatment Outcomes of Hepatocellular Carcinoma Patients who underwent Stereotactic Body Radiotherapy

Objective: To evaluate the prognosis of patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).Material and Methods: A retrospective review was performed of the institutional medical records of patients treated with SBRT. The selection criteria were as follows: unresectable HCC confirmed via pathologically, or through imaging, a Karnofsky Performance Status score &gt;60, any Barcelona Clinic Liver Cancer stage, a Child-Pugh score ≤8, and an uninvolved liver volume &gt;700 cm3 . The primary outcomes were local tumor control, overall survival, and progressionfree survival rates. The secondary outcomes were acute adverse events; including general, gastrointestinal, or hepatic disorders; decreased complete blood count; and increased liver function test results.Results: We included 27 HCC patients treated with SBRT; from August 2013 to October 2019. Moreover, 55.6% of patients had received previous treatments for their SBRT-treated lesions. Additionally, the median volume of internal target volume was 40 cm3 , the median uninvolved liver volume was 1,162 cm3 , and the median radiation dose was 40 Gray: given in five fractions. The 1- and 2-year local tumor control rates were both 79.5%. The 1- and 2-year overall survival rates were 58.8% and 27.6%, respectively, and the median survival was 13 months. There were no grade 4 or 5 acute adverse events observed at initiation of treatment or during the follow-up period. Thirteen percent of patients experienced grade 3 acute adverse events. Three patients experienced radiation-induced liver disease.Conclusion: SBRT can be an effective local treatment for hepatocellular carcinoma in carefully selected patients.

Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points.

BackgroundPrevalence and clinical impact of increased liver function tests in patients affected by Coronavirus disease 2019 (COVID-19) is controversial.AimsThis observational study evaluates the prevalence of transaminases elevation in hospitalized patients affected by COVID-19 and investigates the presence of factors associated with hepatocellular injury and with mortality.MethodsData of 292 adult patients with confirmed COVID-19 admitted to the Ente Ospedaliero Cantonale (Switzerland) were retrospectively analyzed.ResultsTransaminases were increased in about one-third of patients on hospital admission and two-thirds of patients during the hospital stay. On hospital admission, transaminases were more commonly elevated in younger patients, who also reported elevated C reactive protein and a higher degree of respiratory failure. Independent factors associated with abnormal transaminases during hospitalization were drugs, in particular paracetamol (OR=2.67; 95% CI=1.38–5.18; p = 0.004) and remdesivir (OR=5.16; 95% CI=1.10–24.26; p = 0.04). Mortality was independently associated to age (OR = 1.09; 95% CI=1.05–1.13; p<0.001), admission to intensive care unit (OR=5.22; 95% CI=2.28–11.90; p<0.001) and alkaline phosphatase peak (OR=1.01; 95% CI=1.00- 1.01; p = 0.01).ConclusionsOn hospital admission, factors associated with liver damage were linked to demographic and clinical characteristics (age, inflammation and hypoxia) while, during hospitalization, drug treatment was related to development and progression of hepatocellular damage. Mortality was associated with alkaline phosphate peak value.

The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis postliver transplant: A case series.

Cystic fibrosis (CF)-related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease and can progress to need liver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is a cystic fibrosis transmembrane conductance regulator modulator that has superior efficacy compared to previously approved modulators. Use of elx/tez/iva, should be approached with caution in individuals with CFLD or following liver transplantation due to possible increases in liver function tests (LFTs) and drug-drug interactions with several immunosuppressant medications. The purpose of this case series is to explore if the use of elx/tez/iva is safe and tolerable in patients with CF postliver transplantation. A retrospective case series including patients prescribed elx/tez/iva following liver transplantation and an immunosuppressive regimen consisting of drug therapy metabolized by P-glycoprotein was completed. Ten patients at six CF centers with a median age of 22.1 years (range 14-43.4 years) and the median time from the transplant of 6.9 years (range 0.6-22 years) were included. Most patients (8, 80%) received a reduced or full dose of elx/tez/iva for a mean duration of 10.4 months (range 7-12 months). Fluctuations in LFTs occurred in all patients (10, 100%) and led to therapy discontinuation in two patients (20%). Elx/tez/iva initiation resulted in elevations in tacrolimus trough concentration in seven patients (70%). Most patients who tolerated elx/tez/iva had symptomatic and quality of life improvement, increased body mass index, and maintained or improved lung function. Initiation of elx/tez/iva in patients with CF who received liver transplantation may be safe with clinical benefits.

Q Fever in the Differential Diagnosis of COVID 19 Infection

Coxiella burnetii is an intracellular, Gram-negative bacteria and is the causative agent of Q fever, a zoonosis first described in Australia in 1937. It can cause endemics around the world. People usually get the disease by inhaling the contaminated aerosol produced by infected livestock. Contaminated milk, intradermal inoculation, sexual contact, blood transfusion, and transplacental route may also occur. The infective dose for humans is 1-10 bacteria. It is resistant to environmental conditions and can remain alive in animal wastes such as dust and fertilizer. Acute infection is typically asymptomatic or may manifest as a febrile flu-like illness, pneumonia, hepatitis, and central nervous system (CNS) infection. Q fever outbreaks are often caused by occupational exposure that includes shepherds, animal keepers, veterinarians, slaughterhouses or dairy workers, and laboratory personnel working with C. burnetii. During the course of the disease that cannot be distinguished from other pneumonia clinically; 2-10 fold increase in liver function tests, leukocytosis and thrombocytopenia, erythrocyte sedimentation rate and creatine kinase increase may be observed or laboratory findings may be normal. An immunofluorescent antibody (IFA) test, which is a serological reference method, should be requested from patients suspected for the diagnosis of Q fever.

The effect and clinical significance of using nathanson liver retractor on liver function tests in laparoscopic gastric cancer surgery.

There are very few studies in the literature investigating the changes caused by the Nathanson retractors in liver function tests (LFT) after LG and its clinical significance. The present study investigated the changes made by the Nathanson retractor used during LG on LFT and its clinical significance. The data of 236 patients, who underwent radical gastrectomy for primary gastric cancer at Surgical Oncology Unit in the period between January 2015 and January 2020 were retrospective studied. The patients were divided into two groups: laparoscopic gastrectomy (LG; 136 cases) and open gastrectomy (OG; 106 cases). Patients who have undergone cholecystectomy, with primary or secondary liver tumors, with chronic hepatic disease, who have preoperative high ALT, AST and bilirubin values were excluded from the study. LFT were measured preoperatively and postoperative day 1 (LFT1), LFT3, LFT5 and LFT7. LFT: ALT, AST and Total bilirubin (BIL). ALT1, ALT3, ALT5, ALT7 ALT values and AST1, AST3, AST5 AST values of the patients in the LG group were found to be significantly higher (P &lt;0.001). Mean total bilirubin values of the groups were similar (P &gt;0.05). In order to evaluate how the increase in LFT due to the use of the Nathanson retractors reflected on the patients&apos; clinic, we divided the patients who underwent LG into two groups based on ALT increase in ALT1: Normal and Elevated. The in-hospital mortality rates (P = 0.080) and oral nutrition time (P = 0.913) of the groups were similar. No liver infarction developed in any of the groups. The duration of stay in the ICU was significantly longer in individuals with elevated LFT (P = 0.019). Although the use of the Nathanson retractor during LG causes an increase in liver function tests, this does not cause major clinical problems in patients. Key Words: Gastrectomy; gastric cancer; laparoscopy; liver enzymes; liver dysfunciton.

1018P Characterization of liver function tests following tebentafusp in phase III randomized trial comparing tebentafusp with investigator’s choice in first line metastatic uveal melanoma (mUM)

Tebentafusp (tebe) is a bispecific gp100-targeted T-cell receptor fusion protein that can redirect and activate polyclonal T-cells leading to release of inflammatory mediators. In this randomized phase III study in 1L mUM [NCT03070392], tebe demonstrated OS benefit vs. investigator’s choice (IC). Increases in liver function tests (LFTs) were common; however, gp100 is not expressed on hepatocytes and tebe did not redirect T-cells against normal hepatocytes in vitro. Here we describe LFT kinetics and outcomes for tebe and IC-treated patients.

Macrophage activation syndrome in COVID-19

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines – interleukin (IL)-1â, tumor necrosis factor-á, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.