Cases Of Acute Liver Failure Research Articles

S2674 A Rare Case of Acute Liver Failure and Hemophagocytic Lymphohistiocytosis Following Disseminated Histoplasmosis

S2674 A Rare Case of Acute Liver Failure and Hemophagocytic Lymphohistiocytosis Following Disseminated Histoplasmosis

S3499 Acute Liver Failure in an Adolescent With Marijuana Use: A Case Report

INTRODUCTION: Recreational marijuana has been associated with a variety of health hazards. A few case reports have linked the use of marijuana with fulminant liver failure which is considered a rare occurrence. We present an interesting case of acute fulminant liver failure in a young female. CASE DESCRIPTION/METHODS: Our patient is a 21 years old female with a history of asthma presented to our hospital for yellow discoloration to her eyes for 4 days associated with nausea, vomiting, diarrhea, and dark-colored urine. Denied abdominal pain, pale stools, fevers, chills, and dysuria. Reported chronic marijuana use. No drug or alcohol use. Unremarkable family history. Physical examination was positive for yellowish discoloration of the skin and sclera. Initial blood work showed highly elevated liver enzymes alkaline phosphatase at 117 IU/L, aspartate aminotransferase at 745 IU/L, and alanine aminotransferase at 1711 IU/L. Total bilirubin at 7.5 mg/dl with direct bilirubin at 5.2 mg/dl and indirect bilirubin at 2.3 mg/dl. INR at 2 with mildly prolonged prothrombin time but normal partial thromboplastin time. lipase was normal. Abdominal imaging was unremarkable. Urine toxicology was positive for cannabinoids. Infectious, autoimmune, metabolic, and other toxic etiologies of liver injury were ruled out. A liver biopsy was obtained which showed active hepatitis pattern, with hepatocellular dropout involving approximately 20% of the biopsy specimen. The patient was managed supportively. Her liver enzymes were back to normal levels, and she was discharged home. DISCUSSION: Acute liver failure (ALF) is defined as coagulopathy (INR >1.5) and the presence of hepatic encephalopathy of any degree less than 26 weeks duration, in a patient without preexisting liver disease and its commonly caused by drug toxicity (50%), viral hepatitis (9%), and autoimmune hepatitis (7%) with 30–40% of cases with an unknown etiology after an extensive workup as seen in our patient which included viral serologies (HAV, HBV, HCV, CMV), autoimmune and metabolic studies. Liver biopsy showed findings consistent with an active hepatitis pattern with evidence of hepatocyte injury. A presumptive diagnosis of liver toxicity due to marijuana use was assumed. In conclusion, we report a case of a rare cause of ALF induced by chronic marijuana use. Although rare, physicians must have a high index of suspicion to consider this etiology when approaching a case of ALF in adolescent patients with a history of marijuana or other cannabis use.

S2726 No Biopsy Saves Life! Rare Incidence of Liver Transplantation for Unknown T-Cell Lymphoma-Induced Acute Liver Failure

INTRODUCTION: Acute liver failure (ALF) is a rare condition characterized by acute hepatic injury causing rapid onset of coagulopathy and encephalopathy. Without prompt treatment, ALF carries an exceptionally high morbidity and mortality, and prognosis is particularly poor when ALF is attributed to malignant infiltration. We present a case of ALF of initially unknown etiology that required expedited liver transplantation. The patient was subsequently diagnosed with hepatic T-cell lymphoma, which is a potentially transplant disqualifying condition. Post-transplant, the patient completed chemotherapy and made a full recovery. CASE DESCRIPTION/METHODS: A 21-year-old male soldier without prior medical history was evacuated from an overseas deployment for 2 weeks of headaches, fatigue, nausea, and vomiting. Scleral icterus had developed in conjunction with diminished hepatic synthetic function (INR 2.8 not responsive to Vitamin K), hyperbilirubinemia (total bilirubin 12.4 mg/dL), and elevated transaminase levels (ALT/AST 1000/705 U/L). Upon stateside evaluation, he developed asterixis and progressive encephalopathy. The history obtained from the patient was reliably negative for toxic ingestions or suspect environmental exposures. The workup for vascular causes, viral and autoimmune hepatitis, Wilson disease, hemochromatosis, and alpha-1-antitrypsin deficiency was negative. An empiric treatment with n-acetylcysteine was ineffective. Per the ALF Study Group estimation, the patient had a 9% 21-day transplant free survival, and was promptly transferred to a transplant center. A liver biopsy was deferred given coagulopathy and rapid decompensation that required vasopressors and intracranial pressure reduction as a bridge to transplant. His explant demonstrated T-cell rich lymphoma with no hyper-metabolic lesions on PET scan. The patient fully recovered from surgery, completed chemotherapy, and remains in clinical remission on his immunosuppressive regimen. DISCUSSION: Less than 40 cases of ALF from hepatic lymphoma have been reported in the literature, with a majority diagnosed post-mortem. Prognosis is generally poor, and rapid clinical deterioration prompts difficult and swift decisions often based on an incomplete data set. As described with this young patient with ALF of initially unknown etiology, proceeding with liver transplant was the only life-saving option. This case demonstrates that a consideration must be made to transplant potentially disqualifying conditions that have effective established therapies.Figure 1.: Diagnostic CD3 stain for T-cell rich lymphoma.Figure 2.: Diagnostic CD20 stain for T-cell rich lymphoma.

S2660 Imatinib Mesylate (Gleevec)-Induced Acute Liver Failure Successfully Treated With Prednisolone Therapy

INTRODUCTION: Imatinib mesylate (Gleevec) is an FDA approved tyrosine-kinase inhibitor for treatment of resected, high-risk and advanced gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia.1-4% of patients on imatinib therapy develop drug-induced liver injury (DILI) with a minority developing acute liver failure, or even death. We report a clinical case of imatinib-induced acute liver failure in a 46-year-old woman with a GIST of the esophagus/mediastinum successfully treated with corticosteroids. CASE DESCRIPTION/METHODS: A 46-year-old woman with stage IIIa posterior mediastinal GIST at the gastroesophageal junction status post-surgical resection with pathology showing 38 mitosis per high power field on adjuvant imatinib therapy since October 2019 presented in December 2019 with emesis, jaundice and encephalopathy. On exam, she had jaundice and grade 3 hepatic encephalopathy with no focal neurological deficit. The liver associated enzymes revealed elevated ALP 165U/I, ALT 694U/I, AST 635U/I and total bilirubin of 3.0 mg/dL. The ammonia level was 65 uMol/L and INR was 2.3 prompting discontinuation of imatinib.During the hospital course, liver enzymes trended up. Serum assessment for viral hepatitis, autoimmune hepatitis, metabolic liver disease and toxicology testing was negative. Liver ultrasound and abdominal MRI were unremarkable. Liver biopsy revealed extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis (Figure 1). A diagnosis of DILI likely secondary to imatinib was made. After initiation of prednisolone, her encephalopathy and jaundice improved. The liver enzymes and total bilirubin also trended down over a 6 week period (Figure 2,3). DISCUSSION: Imatinib therapy can cause serious side effects, such as acute hepatitis and rarely acute liver failure and death. Liver injury is thought onset varies from 6 days to several years after the initiation of treatment. However, in most cases, acute liver injury develops within a period of 2 to 6 months. Hepatotoxicity usually resolves with either dosage reduction or discontinuation of imatinib. The mechanism of imatinib-induced hepatotoxicity is unknown, however, it has been proposed that imatinib causes immune stimulation. In this case, we successfully employed prednisolone as a novel therapy to treat imatinib induced acute liver failure.This supports the notion that liver injury by imatinib is due to systemic inflammation and direct hepatocyte injury.Figure 1.: extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis.Figure 2.: Liver enzymes trend after initiation of prednisolone therapy.Figure 3.: Biliribin trend.

S2408 Sunitinib-Induced Acute Liver Failure: A Case Presentation

INTRODUCTION: Drug-induced liver injury is an uncommon but a life-threatening entity. Sunitinib, a tyrosine kinase inhibitor (TKI), is used for advanced and imatinib-refractory gastrointestinal stromal tumors. It causes a transient elevation of liver enzymes in about 39% of patients while grade 3 and 4 hepatotoxicities in 3 % of patients. The incidence of fatal acute liver failure is rare. The incidence of acute cardiomyopathy is seen in 10% of patients. We present a case of fatal acute liver failure and cardiomyopathy within two weeks of sunitinib therapy initiation for advanced pancreatic neuroendocrine carcinoma. CASE DESCRIPTION/METHODS: A 64-year-old male with stage IV high grade pancreatic neuroendocrine carcinoma with metastasis to the liver, spleen, and left adrenal gland, presented with right upper quadrant abdominal pain, nausea, and lethargy. The patient was started on Sunitinib, a month prior to presentation. It was discontinued two weeks before admission due to severe fatigue, decreased oral intake, and dehydration. Physical exam was positive for jaundice, disorientation to time, place, and person and asterixis. The trend of liver function tests during the course of hospitalization is presented in Table 1. The workup to determine other causes of acute liver failure was unremarkable. The patient was started on N-acetylcysteine protocol for acute liver failure and lactulose and rifaximin for suspected hepatic encephalopathy. The patient was not a candidate for a transplant due to stage IV cancer. Transthoracic echocardiography showed new-onset severe acute cardiomyopathy with an ejection fraction of 20–25%. The patient's mental status did not improve despite 3–4 bowel movements per day. Despite aggressive supportive care, his liver failure was irreversible and the patient passed away on day 5 of hospitalization. DISCUSSION: Sunitinib causes time and concentration-dependent cellular injury. The pattern of liver injury is typically hepatocellular. Definitive management of organ dysfunction includes withholding of sunitinib along with supportive care. This case emphasizes that overt liver failure and systolic cardiac dysfunction are infrequent but possibly fatal complications of Sunitinib therapy. We recommend periodic monitoring of baseline liver function and cardiac function status for patients on Sunitinib therapy, especially within the first year of treatment.Table 1.: The trend of liver function tests during the course of hospitalization.

S2706 Metastatic Breast Cancer Presenting as Acute Liver Failure

INTRODUCTION: Up to 20% of acute liver failure (ALF) cases have no known etiology. Of the many causes, initial presentation of metastatic carcinoma is rare, with malignant infiltration of the liver usually diagnosed postmortem. We present a case of fulminant liver failure caused by a new diagnosis of metastatic breast cancer. CASE DESCRIPTION/METHODS: A 55 year old African American female with no significant medical history presented with fatigue and jaundice for one month and one week of pruritus and lower extremity edema. On presentation, she had a MELD-Na of 38 with mild confusion, therefore prompting a rapid inpatient liver transplant evaluation for ALF. Physical exam revealed an obese female in no distress, a distended but soft abdomen with hepatomegaly, scleral icterus, and pitting edema. Further history regarding medications and family history was unrevealing other than having immigrated from Liberia in 2000, a history of a positive PPD with negative chest x-ray follow up, and not up to date on cancer screening. An abdominal ultrasound revealed cirrhotic morphology of the liver, ascites, and marked hepatic echogenicity. Paracentesis fluid was negative for SBP with a SAAG of 2.5 and fluid protein <1.0. An abdominal MRI needed for listing revealed an enlarged liver that was replaced by innumerable ring-enhancing lesions concerning for metastasis (Image 1). A non-targeted liver biopsy revealed metastatic carcinoma consistent with breast primary with no underlying cirrhosis (Images 2 and 3). Transplant workup was terminated and the patient was referred to Oncology and Palliative Care for further management. DISCUSSION: Diffuse metastatic breast cancer causing ALF is rare. Like most patients with ALF, our patient had a rapid decline with symptoms specific to hepatic failure only. Confirming prior liver disease is of paramount importance prior to listing which is why a non-targeted biopsy was obtained in our patient prior to receiving the MRI results. This diagnosis of breast cancer presenting as ALF was surprising given the acuity, lack of prior history or symptoms, and signs of cirrhosis. Rare presentations such as this argue towards liver biopsy prior to listing fulminant liver failure patients of unknown etiology, which is currently not required.Figure 1.: MRI.Figure 2.: H&E: liver with metastatic tumor cells.Figure 3.: GATA-3 immunohistochemical stain (IHC): nuclear positivity of tumor cells (specific to breast primary).

S2467 Acute Liver Failure Associated With Therapeutic Doses of Intravenous Acetaminophen

INTRODUCTION: Drug induced liver injury is an uncommon, but important phenomenon responsible for nearly half of all acute liver failure (ALF) cases in the US. The majority of these cases are due to Acetaminophen (APAP) which is hepatotoxic in a dose-dependent pattern. Current guidelines suggest that daily dosing of less than 4 grams a day is safe. However, this dose can be hepatotoxic in patients with underlying liver disease, longer duration of use or malnutrition. The following case demonstrates therapeutic acetaminophen dosing causing acute liver failure. CASE DESCRIPTION/METHODS: A 67-year-old Caucasian female with a BMI of 19.7 kg/m2.was admitted for bowel obstruction due to adenocarcinoma in the sigmoid colon. She had no history of liver disease, alcohol use, acetaminophen use and had normal aminotransferases on admission. The patient remained hemodynamically stable while a pre-surgical evaluation was conducted. She received an average of 3-4g/day of IV APAP for pain over 4 days and was on a liquid diet. On hospital day 5, laboratory evaluation showed an INR of 6.1, which was notably 1.0 before admission, and her liver chemistries were markedly elevated in a hepatocellular pattern. The patient had new psychomotor slowing meeting criteria for ALF. She was not a transplant candidate. Her acetaminophen level was 58.9 mcg/mL 2-hours after her last dose. APAP was discontinued and IV NAC was started. Evaluation of other causes of liver failure to include ultrasound of liver and serologic evaluation for EBV, CMV, HSV, HAV, HBV, HEV, AIH, and Wilson’s disease were unremarkable. Review of her medical record did not reveal any medications to explain her acute liver failure. The patient was closely monitored in the ICU and the coagulopathy, mental status and liver chemistries all improved. A presumptive diagnosis of APAP induced ALF was made. She subsequently underwent an open colectomy without complication. DISCUSSION: While generally safe in therapeutic dosing, we present a case of IV APAP causing ALF. Therapeutic dosing causing hepatoxicity has been associated with malnourishment, low BMI, advanced age, fasting, and longer duration of use. IV APAP has slightly different pharmacodynamics that may increase this risk but has been rarely described. This patient’s fasting state, age and malnutrition likely contributed to ALF. Similar to patient’s with cirrhosis, lower dosing (< 2 G/day) may be more appropriate in this patient population.Table 1.: Hospital Course with Laboratory Data.Figure 1.: Hospital Course with Laboratory Data.Figure 2.: Acetomenophen Dosing during admission.

Two Fatal Cases of Acute Liver Failure Due to HSV-1 Infection in COVID-19 Patients Following Immunomodulatory Therapies.

We reported two fatal cases of acute liver failure secondary to Herpes Simplex Virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy.Screening for and prompt recognition of Herpes Simplex Virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentiallyrelevant clinical consequences.

Adolescent With Acute Liver Failure in the Setting of Ethanol, Cocaine, and Ecstasy Ingestion Treated With a Molecular Adsorbent Recirculating System

Recreational polypharmacy intoxication is a popular trend, particularly among adolescents and young adults. Acute liver failure is an uncommon complication of drug intoxication and has been described separately among patients intoxicated with ethanol, cocaine, and 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy). Many patients with acute liver failure will die without liver transplant, and management of drug-induced acute liver failure is complicated by the fact that polysubstance abuse may be a contraindication for liver transplant, even among young patients.Here we report a case of acute liver failure in an adolescent male secondary to recreational intoxication with ethanol, cocaine, and ecstasy. This patient was not a candidate for liver transplantation. We describe successful treatment using a molecular adsorbent recirculating system (MARS®) or “liver dialysis” and review the literature pertaining to management options for this type of patient.

Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.

In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis. PALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRβ) sequencing. Dense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin (88% vs 50%, P = 0.03) and CD103 (82% vs 40%, P = 0.02) staining compared with DX-PALF subjects. TCRβ sequencing of 15 IND-PALF cases demonstrated increased clonal overlap compared with 6 DX-PALF cases (P = 0.002). Dense infiltration of effector Trm CD8 T cells characterizes liver tissue from IND-PALF subjects. Increased clonality suggests the T-cell expansion is antigen(s)-driven as opposed to a nonspecific inflammatory response. These findings support CD8 staining as a new biomarker of the activated CD8 T-cell PALF phenotype. Future studies are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.

Anti-inflammatory and antioxidant effects of Apium graveolens L. extracts mitigate against fatal acetaminophen-induced acute liver toxicity.

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC-MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hydroxyl radical quenching effect using electron paramagnetic resonance spin trapping technique. Treatment of Acetaminophen-induced hepatotoxicity (AAH) rats with MCRE lowered serum levels of AST, ALT, ALP, TNF-α, and IL-1β significantly. Additionally, MCRE significantly increased total antioxidant capacity (TAC) and glutathione (GSH) levels relative to AAH rats. Strikingly, Kaplan-Meier survival analysis of all groups revealed a 100% prevention of acetaminophen-induced mortality of rats by MCRE pretreatment (100mg/kg/day). MCRE prevented AAH-associated severe weight loss and elicited normal behavior in the rescued rats. Our results suggest that pretreatment with MCRE can mitigate against overdosed acetaminophen-induced acute liver failure and warrant further investigations on the potential of postinjury intervention. PRACTICAL APPLICATIONS: Acetaminophen-induced hepatotoxicity (AAH) accounts for alerting numbers of overdose-related acute liver failure and liver transplant cases with increased morbidity and mortality rates. Currently proposed mechanisms implicate mitochondria-mediated oxidative stress and inflammation in the pathogenesis of AAH, which underline current interventions employing antioxidants to combat liver damage by over-dosed acetaminophen. The present work uncovers potent protective effects of some celery extracts (and their fractions) against acetaminophen-induced oxidative stress and inflammation. Treatment of rats with fatal liver injury with methanol extract of celery root significantly reduced secretion of liver enzymes and markedly decreased inflammatory as well as oxidative stress markers in these animals. This, in turn, rescued challenged rats exposed to fatal doses of acetaminophen completely, which establishes methanol extracts of celery roots as effective therapeutic intervention against AAH. The antioxidant capacity of the extracts was determined using EPR technique, and the secondary metabolites related to antioxidant activity were characterized via UPLC-MS.

Timing of liver transplantation for pediatric acute liver failure due to mushroom poisoning: a case report and literature review

BackgroundPediatric acute liver failure is a rare, life-threatening illness. Mushroom poisoning is a rare etiology. For patients with irreversible pediatric acute liver failure, liver transplantation is the ultimate lifesaving therapy. However, it is difficult to determine the optimal timing of transplantation. Here, we present a case of pediatric acute liver failure due to mushroom poisoning in northeastern China. He was treated with liver transplantation and recovered. To our knowledge, there are few reports about liver transplantation for pediatric acute liver failure caused by mushroom poisoning in mainland China.Case presentationThe patient was a previously healthy 9-year-old boy who gradually developed nausea, vomiting, jaundice and coma within 5 days after ingesting mushrooms. He was diagnosed with mushroom poisoning and acute liver failure. He was treated with conservative care but still deteriorated. On the 7th day after poisoning, he underwent LT due to grade IV hepatic encephalopathy. Twenty days later, he recovered and was discharged. A review of the literature revealed that the specific criteria and optimal timing of transplantation remain to be determined.ConclusionsPatients with pediatric acute liver failure should be transferred to a center with a transplant unit early. Once conservative treatment fails, liver transplantation should be performed.

Experience of National Medical Center of Specialties “La Raza” in the endoscopical management of bile duct complications after liver transplantation

IntroductionLiver transplantation is a standardized treatment for the management of chronic liver failure, as well as, in selected cases of unresectable tumors and acute liver failure. Transplant programs show improvements that impact in the whole survival, however, bile duct complications remain the main cause of morbidity and mortality in transplant programs worldwide. Material and methodsFor statistical purposes, the liver transplant program activity has been divided into 2 Phases, the first one from 2009 to 2017 and the second from 2018 to the present. The files of patients with at least 6 months of follow-up were included. ResultsThroughout the program there is a record of 22 transplants, according to the division mentioned in two Phases, with a total of 9 transplants in 9 years in Phase 1 and 12 transplants in 2 years in Phase 2. With 33% (3) of complications for Phase 1 and 25% (3) for Phase 2.In all patients the management was endoscopic. ConclusionsBile duct complications are associated with identifiable risk factors, however, the patient's evolution is multifactorial. Both the decrease in the frequency of complications and the effectiveness in their management show improvement according to the establishment of the multidisciplinary team of Liver Transplantation.

A case of acute liver failure induced by hepatitis E virus in a patient with chronic alcoholic liver dysfunction

A case of acute liver failure induced by hepatitis E virus in a patient with chronic alcoholic liver dysfunction

Falla hepática aguda en pediatría

Acute liver failure (ALF) is a rare and life-threatening entity in pediatrics which requires a multidis ciplinary approach for early diagnosis and treatment. The objective of this article is to update defi nitions, management, and available treatments. We obtained the articles by reviewing the literature available between 2000 and 2020 in different databases (Pubmed, LILACS, BIREME, Google Scholar, and UpToDate), using terms such as "acute liver failure" in Pubmed, and in other databases "pedia tric acute liver failure" and "falla hepática aguda en pediatría" using filters such as age, publication date, and types of study (clinical trials, review articles, systematic reviews, and case-control studies). We chose those articles with the highest number of citations and with recent data. The ALF requires support in the pediatric intensive care unit and its early diagnosis favors the beginning of treatment. In pediatric patients with ALF, it is recommended to focus on age-specific diagnostic testing. There is no agreement regarding the liver transplantation in pediatric cases of ALF.

CLIF-C Organ Failure Score and Liver Volume Predict Prognosis in Steroid-Treated Severe Acute Autoimmune Hepatitis.

Controversies and debates remain regarding the best management of severe acute‐onset autoimmune hepatitis (SA‐AIH) due to the lack of useful outcome or complication prediction systems. We conducted this clinical practice‐based observational study to clarify whether Chronic Liver Failure Consortium Organ Failure scores (CLIF‐C OFs) and the computed tomography–derived liver volume to standard liver volume (CTLV/SLV) ratio at admission to a tertiary transplant center can predict outcomes and complications due to infection. Thirty‐four consecutive corticosteroid‐treated patients with SA‐AIH from 2007 to 2018 were included. Severe hepatitis was defined as an international normalized ratio (of prothrombin time) over 1.3 any time before admission. Of the 34 corticosteroid‐treated patients with SA‐AIH inclusive of 25 (73.5%) acute liver failure cases, transplant‐free survival was observed in 24 patients (70.6%). Any infection was noticed in 10 patients (29.4%). CLIF‐C OFs, at the cutoff of 9, significantly predicted survival (P = 0.0002, log‐rank test), outperformed the Model for End‐stage Liver Disease system in predicting outcome (P = 0.0325), and significantly discriminated between liver transplant and death in a competing risk analysis. SA‐AIH was characterized as having decreased CTLV/SLV, which was also predictive of survival (P < 0.0001). Interestingly, CLIF‐C OFs, especially the subscores for respiratory dysfunction, also predicted infection (P = 0.007). Conclusion: In corticosteroid‐treated patients with SA‐AIH, CLIF‐C OFs and CTLV/SLV ratios predicted both survival outcome and complications due to infection. Further investigation is warranted to determine whether making decisions based on CLIF‐C OFs or CTLV/SLV ratios is useful.

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use.

Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity, as evidenced by its contribution to over half of all acute liver failure cases in the United States. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.

SARS-COV-2 infection (coronavirus disease 2019) for the gastrointestinal consultant.

The current pandemic due to the severe acute respiratory syndrome coronavirus 2 has caused an extreme burden for health care systems globally, and the number of cases is expected to continue to increase, at least in the immediate future. The virus is estimated to have infected more than 1.5 million individuals. The available reports suggest that gastrointestinal (GI) involvement in coronavirus disease 2019 (COVID-19) is common and in some cases the GI symptoms may precede the respiratory symptoms. In addition to direct effects of severe acute respiratory syndrome coronavirus 2, the infected patients remain at risk for the complications commonly managed by gastroenterology and hepatology consultants. The most commonly reported GI manifestation of COVID-19 is diarrhea, which is reported in a third to up to more than half of the patients. Mild to moderate elevation of the liver enzymes are also common, although no case of acute liver failure has been reported so far. Many of the medications used for treatment of COVID-19 can also be associated with GI symptoms or liver injury and can be included in the differential diagnosis in these patients. Although the diagnosis of the infection is currently based on RNA analysis in respiratory samples, the available literature on fecal shedding of this virus suggests that fecal RNA testing might prove to be a useful diagnostic test. It is reasonable to delay all non-urgent endoscopic procedures during the peak of the pandemic and use additional protective equipment such as N95 respirators during endoscopy while most patients can be considered high risk for having been exposed to the virus.

Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.

Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.

Outbreak control of hospital acquired varicella infection amongst health care workers in a tertiary care hospital

BackgroundAdult and immunocompromised patients suffering from varicella (chicken pox) are potential source of infection to healthcare workers. An outbreak of varicella among healthcare workers in a tertiary care centre was investigated, and preventive measures were implemented. MethodsCases of chicken pox between 05 Feb 2017 and 11 Feb 2017 in a tertiary healthcare establishment were investigated. An epidemiological investigation by developing case definitions, spot map and contact tracing was conducted. Eight cases were identified among healthcare workers. Suitable preventive measures including identification of susceptible contacts and vaccination of susceptible ones with two doses of varicella vaccine was undertaken. ResultsIndex case was a 21-year-old nurse who was exposed to a 34-year-old male patient transferred from a secondary care hospital on 24 Jan 2017 as a case of acute liver failure and coagulopathy. Primary case was later diagnosed as case of varicella based on serological and clinical evidence. Among a total of 8 cases identified in the outbreak, the cases occurred among healthcare workers of secondary care centre, healthcare workers managing the primary case in the intensive care unit and who conducted the autopsy. A total of 181 contacts were identified in the epidemiological investigation, and 54 were susceptible to chicken pox. Two-dose immunization with varicella vaccination of susceptible ones was found to be effective in preventing further cases. ConclusionTwo-dose vaccination of healthcare workers with varicella vaccine is an effective strategy to prevent nosocomial varicella among healthcare workers.