Construction and validation of a novel and severe hepatic injury model in swine focuses on research and training. Observational study.

Some hepatic wound models have been developed in pigs with the aim of reproducing liver injury; however, the wound shape, severity, and outcome differ among them. The novel injury profile employed in this study differed from that used elsewhere for standardized, repeatable, reproducible, incising-penetrating, vascular, and severe injury in swine. It is made with a cutting object that penetrates deep into the hepatic parenchyma, always affecting the two suprahepatic veins at the point where they merge into the common trunk. The primary outcome was reproducibility and replicability of the surgical method. The secondary outcome was the analysis of some variables (blood loss, survival, and flow) to validate the model. •This novel method of liver injury provides a liver injury with the following characteristics: standardized, incise-penetrated, deep, bloody, and severe.•This model can be used for research (trauma, hepato-bilio-pancreatic, pharmaceutical) and training (damage control surgery).•Method name: Incising-Penetrating, Vascular and Severe Liver Injury Model in Swine.

Two cases reports: Severe liver injury caused by 1,2,3-trichloropropane poisoning.

Background: 1,2,3-trichloropropane (TCP) poisoning can induce liver damage in humans and animals, but reports of severe liver injury and its histology are rare. We presented two cases of 1,2,3-TCP inhalation poisoning resulting in severe liver injury confirmed by exposure history, toxicology, biochemical index and pathology. Case description: Two young male presented acute poisoning process with mild to moderate early symptoms, and developed severe jaundice and coagulation dysfunction after exposure to 1,2,3-TCP. The total bilirubin (TBIL) in case 1 and case 2 reached the peak value of 635.8 µmol/L and 437.1 µmol/L on the 25th and 22nd days, respectively. Their liver enzymes and international normalized ratio increased rapidly to peak and fell back, and TBIL remained at a high level. 1,2,3-TCP was detected in their blood, and their liver histology indicated severe necrosis of hepatocytes, infiltration of massive inflammatory cells, and cholestasis. They all finally recovered after a long time of treatment. Conclusion: The two cases in this study demonstrate that 1,2,3-TCP inhalation poisoning without any protective measures can induce severe liver injury in humans.

Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis.

BACKGROUND: Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors. METHODS: We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. We used CMA software for statistical analysis. RESULTS: Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42-60%, I2 = 91%), viral hepatitis was 13.1% (95% CI 9.7-17.6%, I2 = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I2 = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4-13.6%, I2 = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9-44.8, P value < 0.0001, I2 = 64% Q 11.1). DISCUSSION: This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000 IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.

Depacked patients who underwent a shortened perihepatic packing for severe blunt liver trauma have a high survival rate: 20 years of experience in a level I trauma center.

INTRODUCTION: Non-operative management is currently the preferred approach in blunt liver trauma, including high grade liver lesions. However, hemodynamic instability imposes the need for an emergency laparotomy, with a perihepatic packing (PHP) to control liver bleeding in most cases. Our retrospective study aimed to assess the outcomes of liver trauma patients who underwent a shortened PHP. METHODS: All consecutive patients who underwent PHP for blunt liver trauma from 1998 to 2019 in our Level I trauma center were included in the study. Unstable patients with severe liver trauma were transferred to the operating room without any delay, and a collective decision was made to perform abbreviated laparotomy to pack the liver. Demographics, perioperative data, postoperative outcomes, and mortality were retrospectively collected, and survivors and deceased patients were compared with a paired t-test. RESULTS: Fifty-nine patients of 206 patients admitted with severe liver injuries were treated with shortened PHP. Thirty-four (57.6%) patients died, including 26 (76.5%) within the first 24 h. Twelve (20.3%) patients had a selective hepatic embolization and eight (13.6%) had an extrahepatic embolization. Forty-eight patients had an extra abdominal associated injury. This was not a predictive factor of mortality. The removal of packing was performed in 24 patients within 72 h after laparotomy, with an 80% survival rate in these patients. CONCLUSION: Shortened PHP is an effective strategy for controlling liver bleeding in severe hepatic trauma. The mortality rate of these patients is high, but after the removal of packing, the survival is good.

Impact of COVID-19 pandemic on liver, liver diseases, and liver transplantation programs in intensive care units.

Emerging worldwide data have been suggesting that coronavirus disease 2019 (COVID-19) pandemic consequences are not limited to the respiratory and cardiovascular systems but encompass adverse gastrointestinal manifestations including acute liver injury as well. Severe cases of liver injury associated with higher fatality rates were observed in critically ill patients with COVID-19. Intensive care units (ICU) have been the center of disposition of severe cases of COVID-19. This review discusses the pathogenesis of acute liver injury in ICU patients with COVID-19, and analyzes its prevalence, consequences, possible drug-induced liver injury, and the impact of the pandemic on liver diseases and transplantation programs.

Diagnosis of erythropoietic protoporphyria with severe liver injury: A case report.

BACKGROUND: Porphyria is a rare disease with complex classification. Erythropoietic protoporphyria (EPP) is an autosomal recessively inherited disease, and most are caused by mutations in the FECH gene. EPP combined with liver injury is even rarer. CASE SUMMARY: This paper reports a case of EPP which was admitted to the hospital with abnormal liver function and diagnosed by repeated questioning of medical history, screening of common causes of severe liver injury, and second generation sequencing of the whole exon genome. We also summarize the clinical characteristics of EPP with liver injury, and put forward some suggestions on EPP to provide a reference for the diagnosis of such rare disease. CONCLUSION: A new mutation locus (c.32_35dupCCCT) which may be related to the disease was found by detecting the FECH gene in the pedigree of this case.

Potential value of urinary amatoxin quantification in patients with hepatotoxic mushroom poisoning.

BACKGORUND & AIMS: Mushroom poisoning with Amanita phalloides or similar species can lead to liver failure with 10-30% mortality rates. We aimed at defining the prognostic value of urinary amatoxin quantification in patients with hepatotoxic mushroom poisoning. METHODS: Data from 32 patients with hepatotoxic mushroom poisoning (Hospital Clínic Barcelona, 2002-16) in whom urinary amatoxins were determined (ELISA) were retrospectively reviewed. Correlations between urinary amatoxin and collected baseline variables with outcomes including hepatotoxicity (ALT>1000 U/L), severe acute liver injury (ALI, prothrombin <50%), acute liver failure (ALF, ALI and encephalopathy), transplantation/death and hospital length-of-stay, were evaluated. RESULTS: 12/32 patients developed increased aminotransferase activity. Among the 13/32 amatoxin negative patients, 1 developed ALI and 12/13 no hepatotoxicity. Among the 19/32 amatoxin positive patients, 8/19 (42%) developed hepatotoxicity, including 5 who progressed to severe ALI, of whom 3 developed ALF (2 deaths, 1 transplantation). Urinary amatoxin and prothrombin were independent predictors of hepatotoxicity, ALT peak values (along with age) and hospital length-of-stay. In positive amatoxins patients, urinary concentrations > 55 ng/ml (or a baseline prothrombin ≤ 83%), were associated to hepatotoxicity (presented by 8/9 patients with ALT>1000 U/L). Among 5 patients with urinary amatoxin ≥ 70 ng/ml, 4 developed severe ALI. CONCLUSIONS: In patients with hepatotoxic mushroom poisoning, a negative urinary amatoxin quantification within 72h of intake ruled out the risk of hepatotoxicity in 92% of patients, whereas positive urinary amatoxins were associated with hepatotoxicity and severe ALI. Concentrations >55 ng/ml and ≥ 70 ng/ml were predictive of hepatotoxicity and severe ALI, respectively.

Severe hepatic injury for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis / 中华风湿病学杂志

Objective To analyze the clinical features and laboratory data of 10 patients with macrophage activation syndrome (MAS) complicating systemic onset juvenile idiopathic arthritis (soJIA),which were characterized by acute severe liver injury.Methods Data of 10 patients with soJIA/MAS from Nanjing Children's Hospital were collected retrospectively.The clinical features,laboratory findings,treatment,outcomes and prognosis were analyzed.Results In the total 10 patients,female (6/10) outnumbered male.Their age ranged from 1.5 to 9.5 years old (average 5.2±2.6).The most remarkable clinical manifestations were severe liver injury without systemic features,representing as hepatomegaly (10/10),splenomegaly (2/10) and strikingly increased transaminase (10/10,median:ALT 1 445 U/L,AST 885 U/L).Central nervous system dysfunction and hemorrhages were recorded in 20％ of the patients.Two patients had pulmonary infection.Laboratory data showed that platelet count was less than normal or precaution value (10/10,≤262×10g/L).Hyperferritinaemia (10/10,median:17 329 mg/ml) and soluble CD25 elevation (median:3 140 U/ml) were common in the soJIA/MAS patients.Evidence of macrophage hemophagocytosis was found in 90％ of the patients (9/10) who underwent bone marrow aspiration.Pathological findings of liver biopsy from 1 patient revealed massive infiltration of mononuclear cells in the portal tracts.Nearly all patients (9/10) received intravenous pulse methylprednisolone therapy,combined with cyclosporine A and high-dose intravenous immunoglobulin.Eight patients had good outcome.Only 2 patients were complicated with severe interstitial lung disease during 12-months follow-up.Conclusion MAS should be considered when patients with soJIA represents acute severeliver injury without systemic features combined with other laboratory data.Intravenous pulse methylprednisolone and cyclosporine A therapy may improve the prognosis of soJIA/MAS.

Selective vascular isolation of the liver as part of initial damage control for grade 5 liver injuries: Shouldn't we use it more frequently?

BACKGROUND: Severe liver trauma (grade 4 and 5) carries mortality greater than 40%. It represents a major surgical challenge in patients with hemodynamic instability who require an immediate exploratory laparotomy. Perihepatic packing and damage control can sometimes work, but for severe liver injuries, adjunct maneuvers might be needed (such as early embolization or hepatic artery ligation). During a patient's first operation for severe liver trauma, anatomic resection is rarely tolerated. MATERIALS AND METHODS: We managed a 31 year-old male with a blunt grade 5 right-lobe liver injury in severe hypovolemic shock. RESULTS: As part of the initial damage control operation, concurrently with intermittent Pringle maneuver, he underwent intra- and perihepatic packing; selective isolation and ligation of the right portal vein, right hepatic artery, and right hepatic vein; and repair of the retrohepatic inferior vena cava. Then, 36h later, the patient underwent a right hepatectomy. CONCLUSION: For patients with severe liver injuries, selective vascular isolation and ligation may be considered as part of damage control (in addition to intermittent Pringle maneuver) and might enable anatomic resection at a later stage.

Angiointervention: an independent predictor of survival in high-grade blunt liver injuries.

BACKGROUND: The role of angiointervention (ANGIO) in the management of high-grade liver injuries is not clear and there are concerns about increased complications. METHODS: National Trauma Data Bank study, isolated grade IV and V blunt liver injuries. Patients with major associated intra-abdominal or extra-abdominal injuries were excluded. Logistic regression analysis was performed to identify independent predictors of mortality and complications. RESULTS: Six thousand four hundred two patients met the criteria for inclusion. Laparotomy was performed in 32% of the patients and nonoperative management in 68%. Overall, 11% of the patients underwent ANGIO. Patients in the ANGIO group were significantly more likely to be older than 55 years than non-ANGIO patients and more likely to have Injury Severity Scores greater than 25. After stepwise logistic regression, ANGIO was an independent predictor of survival (P < .001). In the group of patients managed operatively, it was independently associated with a lower mortality (P < .001). Similarly, in the nonoperative group, it was independently associated with a lower mortality (5.4% vs 9.5%, P = .008). ANGIO was associated with increased systemic complications. CONCLUSIONS: ANGIO in blunt, severe liver injuries is associated with reduced mortality and increased complications, in both operative and nonoperative management.