Liver Failure Research Articles

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

Prognostic value of inflammation-related model in hepatitis B acute-on-chronic liver failure

Prognostic value of inflammation-related model in hepatitis B acute-on-chronic liver failure

Diacerein ameliorates thioacetamide-induced hepatic encephalopathy in rats via modulation of TLR4/AQP4/MMP-9 axis

AbstractAstrocyte swelling, blood brain barrier (BBB) dissipation and the subsequent brain edema are serious consequences of persistent hyperammonemia in hepatic encephalopathy (HE) in which if inadequately controlled it will lead to brain death. The current study highlights the potential neuroprotective effect of diacerein against thioacetamide (TAA)-induced HE in acute liver failure rat model. HE was induced in male Sprague–Dawley rats via I.P. injection of TAA (200 mg/kg) for three alternative times/week at 3rd week of the experiment. Diacerein (50 mg/kg) was gavaged for 14 days prior to induction of HE and for further 7 days together with TAA injection for an overall period of 21 days. Diacerein attenuated TAA-induced HE in acute liver failure rat model; as proofed by significant lowering of serum and brain ammonia concentrations, serum AST and ALT activities and significant attenuation of both brain and hepatic MDA contents and IL-1β with marked increases in GSH contents (P < 0.0001). The neuroprotective effect of diacerein was demonstrated by marked improvement of motor and cognitive deficits, brain histopathological changes; hallmarks of HE. As shown by immunohistochemical results, diacerein markedly downregulated brain TLR4 expression which in turn significantly increased the GFAP expression, and significantly decreased AQP4 expression; the astrocytes swelling biomarkers (P < 0.0001). Moreover, diacerein preserved BBB integrity via downregulation of MMP-9 mediated digestion of tight junction proteins such as occludin (P < 0.0001). Collectively, diacerein ameliorated cerebral edema and maintained BBB integrity via modulation of TLR4/AQP4/MMP-9 axis thus may decrease the progression of HE induced in acute liver failure.

Can Talaromyces marneffei Infection Cause Acute Liver Failure? A Case Report

Introduction: Talaromyces marneffei is a pathogen that causes talaromycosis, a systemic fungal infection. Cases in which hepatic failure is the primary clinical presentation are exceedingly rare. Case Presentation: This report details the case of a 49-year-old male with no prior liver disease, presenting to the hospital with persistent symptoms, including a fever lasting over ten days, abdominal distension for five days, and jaundice for three days. The patient’s history included immune thrombocytopenia and prolonged glucocorticoid therapy. Physical examination revealed yellowing of the skin and sclera, abdominal distension, firmness of the abdominal wall, absence of abdominal tenderness, positive shifting dullness, and pitting edema in the lumbosacral region and bilateral lower extremities. An HIV antibody test was negative. The patient developed hepatic failure and received artificial liver support along with routine therapy. Despite these interventions, the patient was automatically discharged without improvement and subsequently passed away. Post-discharge, cultures from pleural and abdominal effusions identified Talaromyces marneffei. Conclusions: Talaromyces marneffei infection should be considered in the differential diagnosis of immunocompromised patients, particularly those with no history of liver disease but with long-term glucocorticoid or immunosuppressant use who present with acute liver failure. Early and aggressive investigation for the causative pathogen is essential to minimize diagnostic and treatment delays. Given the prolonged incubation period of Talaromyces marneffei, metagenomic next-generation sequencing may offer a more rapid approach for etiological diagnosis.

Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days.Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.

Prior metabolic and bariatric surgery is an independent determinant of severity of decompensation in alcohol-associated liver disease.

Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder, potentially resulting in end-stage liver disease, with a paucity of data on the evolution of cirrhosis. Our aim was to describe the demographics and mortality in hospitalizations over time in individuals diagnosed with cirrhosis due to alcohol-associated liver disease (ALD) in relation to prior MBS. We included patients hospitalized at the Ghent University Hospital between 1/1/2010 and 01/09/2023 with cirrhosis due to ALD. Data were retrieved retrospectively from all hospitalizations. 46/275 (16.7%) of individuals with cirrhosis admitted with ALD had a history of MBS; they were predominantly female (76.1%), in contrast to the non-MBS population (29.7%) (p<0.0001) and were significantly younger at the time of diagnosis (46 vs. 58years, p<0.0001). Liver disease evolved at a faster pace in the MBS group with a shorter time to first hospitalization (5 vs. 13months, p=0.036), and consecutive hospitalizations. The proportion with primary hospitalization due to acute-on-chronic liver failure (ACLF) was significantly larger in the MBS group (60.9% vs. 27.6%, p<0.0001), and throughout the following hospitalizations, ACLF remained more prevalent in the MBS group. Modeled transplant-free survival was lower in the MBS group (p=0.004), with ACLF as the main cause of death. The weekly amount of alcohol consumed during drinking periods and duration of use were significantly lower in the MBS group. MBS patients hospitalized with ALD develop acute decompensation at a faster pace, with more overall ACLF hospitalizations, and higher cumulative mortality, despite being 12years younger on average. Not applicable.

Protective Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Internal Medicine (Part 1)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a revolutionary class of drugs with far-reaching protective effects in multiple organs. The protective potential of SGLT2i is much broader than that of the classical concept of glucose control and consists of an entire conglomerate of associated pleiotropic effects. This study aims to provide a descriptive review of the pleiotropic therapeutic potential of SGLT2i. The first part of the literature review examined the use of SGLT2i in cardiology and nephrology. The use of SGLT2i represents an innovative approach to improving patients’ quality of life and course of heart failure and chronic kidney disease, regardless of left ventricular ejection fraction and type 2 diabetes.

Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis.

Managing Multiorgan Failure in Acute on Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.

Systemic capillary leak syndrome.

The vascular endothelial barrier maintains intravascular volume and metabolic homeostasis. Although plasma fluids and proteins extravasate continuously from tissue microvasculature (capillaries, post-capillary venules), systemic vascular leakage increases in critical illness associated with sepsis, burns and trauma, among others, or in association with certain drugs or toxin exposures. Systemically dysregulated fluid homeostasis, which can lead to hypovolaemia, hypotensive shock and widespread tissue oedema, has been termed systemic capillary leak syndrome (SCLS) when overt secondary causes (for example, heart or liver failure) are excluded. In severe forms, SCLS is complicated by compartment syndrome in the extremities and multi-organ dysfunction syndrome due to shock and systemic hypoperfusion. The different forms of SCLS include idiopathic SCLS (ISCLS) and secondary SCLS(SSCLS), which can be triggered by several conditions, including certain infections and haematological malignancies. A subgroup of patients with ISCLS have monoclonal gammopathy-associated SCLS (also known as Clarkson disease), which is an ultra-rare and extreme form of ISCLS. ISCLS can be managed effectively with monthly prophylactic immunoglobulin therapy whereas SSCLS frequently does not recur once the underlying condition resolves or the offending agent is discontinued. Thus, differentiation between ISCLS, SSCLS and other causes of oedema is crucial for quick diagnosis and positive patient outcomes.

Liver Failure in Autoimmune Hepatitis Overlap Syndrome With Primary Biliary Cholangitis: A Case Report

Liver Failure in Autoimmune Hepatitis Overlap Syndrome With Primary Biliary Cholangitis: A Case Report

Determination of prothrombin time by the Ovren method in recipients after liver transplantation from a donor diagnosed with brain death

Objective. To evaluate a new method for diagnosing the state of the hemostatic system in patients with hepatobiliary pathology who underwent liver transplantation from a donor diagnosed with brain death. Materials and Methods. A pilot prospective study was conducted involving 10 patients with liver cirrhosis of various etiologies who underwent liver transplantation from a donor diagnosed with brain death. Laboratory parameters of liver function were analyzed perioperatively, during the first 5 days, on the 10th and 14th day after surgery and before discharge or death. The correlation of the prothrombin time by Ovren with the prothrombin time by Quick and with the international normalization ratio was determined using the Spearman rank correlation coefficient. Values of p ˂0.05 were considered statistically significant. Results. The mean number of points on the scale for assessing the severity of liver failure (MELD) before surgery was 27.7 ± 6 (minimum – 15, maximum – 36), which corresponded to severe class C liver failure. The correlation between the value of prothrombin time according to Quick and according to Ovren, as well as between the values of the international normalized ratio and prothrombin time according to Ovren was statistically significantly negative: rs = –0.85315, p (two–sided test) = 0.00042 and rs = –0.90527, p (two–sided test) ˂0.05, respectively. The Ovren prothrombin time was 48% on the 5th day after surgery, after which the functions and reserves of coagulation normalized starting from the 10th day, which is conveniently assessed by an increase in this indicator to 74.5% and above. Conclusions. Determination of the prothrombin time by Ovren can improve the diagnosis of liver failure and monitoring of liver function recovery in patients after liver transplantation from a donor diagnosed with brain death.

Single-Center Survey of Prevalence of Viruses in Pediatric Liver Explants.

Adenovirus has been implicated as a cause of acute liver failure (ALF) following a global outbreak of adenovirus-associated ALF in 2021. To understand any association between viral infection and ALF, it is important to know the baseline prevalence of that virus in children undergoing liver transplant for acute and chronic liver disease (CLD). Our objective was to perform retrospective evaluation of prevalence of common hepatotropic viruses among children who underwent liver transplant at our center. We studied 33 stored frozen hepatic explant samples (originally collected between 2004 and 2021 as part of a liver repository) which fell into three categories: ALF (n = 18), acute on chronic liver failure (ACLF, n = 7), and CLD (n = 8). DNA was extracted from the samples, and viral PCR testing was performed for adenovirus, EBV, CMV, and HHV-6. Adenovirus was detected in a single case of indeterminate ALF transplanted in 2019. CMV was detected in two cases, and there were no EBV positive specimens in any group. HHV-6 was more prevalent with 21 of 33 specimens testing positive including ALF, ACLF, and CLD cases. This retrospective study of common childhood virus prevalence in liver explants provides important baseline information for studying potential viral etiologies of ALF. We did not identify any clusters of infections. The most frequently occurring virus and only virus found in all categories was HHV-6, underscoring the high prevalence in this heterogenous group. Adenovirus was identified in 1 out of 18 of ALF samples, but likely was not a hepatic pathogen.

Convergence of Alcohol Consumption and Dietary Quality in US Adults Who Currently Drink Alcohol: An Analysis of Two Core Risk Factors of Liver Disease

Background/Objectives: Alcohol consumption and poor dietary habits are on the rise in the United States, posing significant challenges to public health due to their contribution to chronic diseases such as liver failure. While associations between alcohol consumption patterns and diet quality have been explored, the relationship between specific alcoholic beverage types and diet quality remains underexamined. This study aims to compare diet quality among consumers of different alcoholic beverage types. Methods: We conducted a cross-sectional analysis of 1917 current alcohol drinkers from the National Health and Nutrition Examination Survey (NHANES) who completed a 24 h dietary recall survey. Diet quality was assessed using the Healthy Eating Index (HEI), with higher scores indicating superior diet quality. Multivariable logistic regression models were employed to assess differences in HEI between consumers of various alcoholic beverage types, using wine-only drinkers as the reference group and controlling for demographic, socioeconomic, lifestyle, and metabolic syndrome variables. Results: Beer-only drinkers were more likely to have lower income, higher rates of cigarette smoking, and insufficient physical activity compared to other alcohol consumers. In the fully adjusted multivariable model, beer-only drinkers had an HEI score that was 3.12 points lower than wine-only drinkers. In contrast, liquor/cocktail-only and multiple-type drinkers had similar HEI scores to wine-only drinkers. Conclusions: Beer-only consumption is associated with poorer diet quality among alcohol drinkers. Targeted patient education and public health campaigns may be effective in addressing the combined impact of alcohol consumption and poor diet quality on chronic disease risk.

Relationship between liver and cardiometabolic health in type 1 diabetes

IntroductionType 1 diabetes (T1D) is a chronic condition marked by insulin deficiency and hyperglycemia, with an increasing global incidence, particularly among children. Despite improvements in diabetes management, individuals with T1D continue to experience higher rates of cardiovascular disease (CVD), the leading cause of mortality in this population. Traditional CVD risk factors such as dyslipidemia and poor glycemic control are insufficient to fully explain the elevated risk in T1D, prompting further investigation into additional factors. Emerging evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) plays a critical role in this heightened CVD risk.ObjectiveThis narrative review aims to explore the relationship between MASLD and CVD in individuals with T1D. The review focuses on the prevalence of MASLD, its contributing risk factors, and the potential impact of liver dysfunction on cardiovascular outcomes in this population.MethodsA review of existing literature was conducted, focusing on observational studies, cohort studies, and meta-analyses that investigate the prevalence of MASLD in T1D populations and its association with CVD. The review also examines the physiological mechanisms linking MASLD and CVD, including insulin resistance, systemic inflammation, and hepatic dyslipidemia. Key studies were evaluated to identify patterns in MASLD prevalence based on diagnostic modalities and to assess the independent contribution of MASLD to cardiovascular risk in T1D patients.ConclusionMASLD is increasingly recognized as a significant contributor to CVD in individuals with T1D, particularly in those with shared risk factors like obesity and insulin resistance. Evidence suggests that MASLD exacerbates hepatic and systemic metabolic dysfunction, increasing CVD risk through mechanisms such as chronic inflammation and atherogenic lipid profiles. Routine liver health assessments and tailored management strategies targeting MASLD should be incorporated into clinical care for individuals with T1D to mitigate long-term cardiovascular complications.

HPB SO64 - Outcomes of liver resection for hepatocellular cancer with or without liver functional assessment using Tc 99m Mebrofenate SPECT-CT, portal pressures: A comparative study

Abstract Background Presence of background liver disease increases the post operative morbidity and mortality among patients undergoing liver resection for hepatocellular carcinoma (HCC). These patients need evaluation of background liver function and portal hypertension, in addition to the conventional risk assessment. The current study aims to look at the outcomes of liver resections performed for HCC cases comparing cohorts with conventional risk assessment (CA) and those with functional assessment (FA) of background liver. Method A retrospective study including all liver resections for HCC cases performed in our tertiary care hepatobiliary unit between 2013 and 2022 (10 years) was conducted. A pathway for liver functional assessment using Tc 99m Mebrofenate SPECT-CT, and portal pressures (cut-off values of 2.79/min/m2 and 10mmHg, respectively) was included in the departmental protocol in December 2018. Data on demographics, underlying degree of liver cirrhosis, types of liver resection and post-operative outcomes including post-hepatectomy liver failure (PHLF) were collected and reported using descriptive statistics. Results 200 liver resections, performed for HCC between 2013 and 2022, were divided into a conventional (126 patients) and functional (74 patients) assessment groups. Median age (68 years) was similar. Background liver cirrhosis was present in 27 (21%) vs 19 (26%) cases, and major resections were performed in 47 (37%) and 10 (13%) cases in the CA and FA groups respectively. In the CA group, 90-day mortality was 7% (compared to FA group (1%) (p=0.26). None of the patients in FA group was found to have PHLF whereas 3 patients each had PHLF grade B and C in the conventional group. Conclusion Formal functional assessment of the background liver by evaluating the function of future liver remnant and presence of portal hypertension helps in selection of patients for appropriate surgical treatment options and improve the post-operative outcomes.

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction.

HPB SO02 - Cutting surgical site infection rates in perihilar cholangiocarcinoma with informed changes to perioperative antibiotic prophylaxis: A quality improvement project in a UK hepatopancreatobiliary tertiary centre

Abstract Background Perihilar cholangiocarcinoma (pCCA) is the most common cancer of biliary epithelia. While potentially curative, surgical resection is associated with high morbidity and mortality. Surgical site infections (SSIs) are common and pernicious. Preoperative biliary instrumentation is universal: to confirm histological diagnosis and deploy stents to relieve jaundice. Patients receive multiple antibiotic courses as periprocedural prophylaxis and to treat cholangitis. They are at high risk of harbouring bacteria not quelled by perioperative prophylactic antibiotics given for other general surgical procedures. Studying the biliary microbiome, this quality improvement project sought to reduce SSIs through informed changes to local guidelines on perioperative antibiotic prophylaxis. Method Health records of all patients undergoing resection for pCCA in a UK hepatopancreatobiliary centre from February 2009 to January 2024 were analysed retrospectively (n=118). For all patients, we routinely sent intraoperative bile swabs for culture and sensitivity. Informed by these microbiology results, multidisciplinary discussion led to changes to local guidelines in March 2019. Formerly, cefuroxime and metronidazole were given on anaesthetic induction, with subsequent antibiotic choice and duration according to surgeon preference. New guidance stipulated teicoplanin and piperacillin/tazobactam be given on induction and for 72 hours postoperatively. We studied the impact of these changes on SSIs within 30 days. Results 75 patients received cefuroxime and metronidazole; 43 patients were given teicoplanin and piperacillin/tazobactam after the policy change. Proportions of patients who developed any SSI substantially fell following the guideline change (55% v 28%; p=0.0049), primarily owing to reductions in intraperitoneal collections (39% v 21%; p=0.047). Rates of deep (8% v 2%; p=0.21) and superficial incisional infections (8% v 5%; p=0.49) were not significantly affected. Associated secondary outcomes were drops in post-hepatectomy liver failure (17% v 5%; p=0.047), and 90-day mortality (16% v 5%; p=0.067), albeit the latter was not statistically significant. Conclusion Invasive investigative work-up, disease complications and exposure to multiple courses of antibiotics prior to resection of pCCA subject patients’ biliary systems to colonisation with antimicrobial-resistant bacteria. We urge centres that undertake these operations to introduce intraoperative bile cultures as a part of routine practice to inform local guidance on perioperative antimicrobial prophylaxis. We demonstrated effective antibiotics in the perioperative period can have enormous benefits to patient outcomes.

HPB SO20 - Evaluating the Impact of Enhanced Recovery After Surgery Protocols Post Hepatectomy in Patients with Chronic Liver Disease: A Meta-Analysis

Abstract Background Defined criteria for the resectability of liver disease continue to be refined. In the era of enhanced recovery after surgery (ERAS), data regarding its safety and efficacy in specific patient populations is required. Patients with liver cirrhosis are particularly vulnerable, owing to both operative and peri-operative risk. However, the application of ERAS in cirrhotic patients undergoing hepatectomy is absent from the most recent ERAS Society Group recommendations from 2022. We present a meta-analysis assessing outcomes after liver resection in patients with cirrhosis following an ERAS protocol compared to standard post-operative care. Method A systematic literature search was performed using PubMed, Embase and Web of Science. Studies were included if comparing ERAS protocols versus standard post-operative care in patients undergoing liver resection in which more than 50% of the patient population had cirrhosis at time of surgery. The primary outcome analysed was overall complication rates with secondary outcomes of post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission and reoperation rates. Statistical analysis was performed using Review Manager by the Cochrane Collaboration. Results 930 records were screened for eligibility. Five articles were eligible for inclusion(ERAS n = 425 vs control group n = 423 patients). Cirrhotic patients enrolled in an ERAS program post-hepatectomy had a significantly reduced risk of overall complications (OR 0.45, 95% CI 0.33, 0.61, p&amp;lt;0.00001) and a shorter hospital stay when compared to standard post-operative care by 1.8 days (mean difference -1.83, 95% CI -2.22, -1.45, p&amp;lt;0.00001). No significant differences were noted in post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission or reoperation rates between the ERAS group and control. Conclusion Application of an ERAS protocol for patients undergoing liver resection is safe and feasible in cirrhotic patients. ERAS protocols were successful in significantly reducing overall complication rates and length of inpatient hospital stay, and did not negatively impact secondary post-operative outcomes or mortality. ERAS protocols should be reflected in future guidelines, specifically for cirrhotic patients undergoing hepatectomy, and additional research on the utility of ERAS in higher risk patients is encouraged.

Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis.

Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl4) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1-deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.