Risk Of Liver Dysfunction Research Articles

Liver Dysfunction in a Patient with Graves' Disease.

Liver dysfunction can occur in patients presenting with thyrotoxicosis, due to several different aetiologies. A 42-year-old man had mild liver dysfunction on presentation with hyperthyroidism due to Graves' disease (GD): ALT 65 (0-45 IU/L), fT4 41.2 (9-23 pmol/L), fT3 > 30.7 (2.4-6 pmol/L), and TSH < 0.01 (0.3-4.2 mIU/L). His liver dysfunction worsened following the initiation of the antithyroid drug (ATD) carbimazole (CBZ), with ALT reaching a zenith of 263 IU/L at 8 weeks following presentation. Consequently, CBZ was stopped, and he was managed with urgent radioiodine therapy. His liver function tests (LFTs) improved within 1 week of stopping carbimazole (ALT 74 IU/L). Thionamide-induced liver dysfunction is more typically associated with a 'cholestatic' pattern, although he had a 'hepatitic' pattern of liver dysfunction. The risk of liver dysfunction in GD increases with older age and higher titres of thyroid-stimulating hormone receptor antibody (TRAb). This review of the literature seeks to explore the possible causes of liver dysfunction in a patient presenting with hyperthyroidism, including thyrotoxicosis-induced liver dysfunction, ATD-related liver dysfunction, and the exacerbation of underlying unrelated liver disease.

Combined impact of alcohol consumption and metabolic syndrome on liver dysfunction in an elderly Chinese population

Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.

Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study

BackgroundAbnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. MethodsThe multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. FindingsPSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings. InterpretationSARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population.Funding 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

Higher urinary glyphosate exposure is associated with increased risk of liver dysfunction in adults: An analysis of NHANES, 2013-2016.

Glyphosate (GLY) exposure, both exogenous and endogenous, is a global concern. Multiple studies of model systems in vitro and in vivo have demonstrated the potential toxic effects of GLY exposure on human organs, particularly the liver and renal system. However, there is currently limited epidemiological evidence establishing a link between GLY exposure and hepatorenal function in the general population. In this study, a multivariable linear regression model and forest plots were employed to evaluate the connection between urinary GLY and biomarkers of hepatorenal function in 2241 participants from the National Health and Nutrition Examination Survey 2013-2016. Additionally, subgroup analyses were conducted based on age, gender, race, BMI, and chronic kidney disease (CKD). Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT and fibrosis 4 score (FIB-4) all increased with elevated urinary GLY concentrations after adjusting for potential confounders, while albumin (ALB) exhibited the opposite trend, particularly among younger, female, non-Hispanic white, overweight, and CKD participants. Furthermore, individuals in the third tertile had a greater risk of liver dysfunction than those in the first tertile after categorizing urinary GLY concentrations. However, our study showed no proof that GLY exposure affects the ratio of urine albumin to creatinine (ACR) or serum creatinine levels. Overall, these results imply that GLY exposure may have adverse effects on human liver function.

The Role of the Gut Microbiome and the Hepatic Axis in the Pathogenesis of Metabolic Syndrome and Therapeutics

The increased global prevalence of viral and noninfectious liver illnesses has coincided with a surge in scientific interest in gut microbiota (GM), a multispecies community of bacteria, fungi, archaea, and protozoans. Dietary nutrients that make up the host’s microbiome are responsible for maintaining intestinal homeostasis, whereas a disconnect between gut flora and nutrition might have serious consequences for digestive health. The risk of liver dysfunction was continuously elevated by changes in the commensal bacteria of the gut microbiome, which were carried to the liver via the portal vein. Insights into the role of gut microbiota in alcoholic liver disease, nonalcoholic liver disease, primary sclerosing cholangitis, and other liver disorders, as well as their link to liver cancer, continue to emerge. Systemic host defence against infections by the gut microbiota depends on the interplay between the microbiome, liver immunology, and liver disorders. Translocation of microbiota to the liver following injury and/or inflammation may mediate dysbiosis and the formation of gut microbial metabolite. This review discusses the role of the gut microbiota in connection to dysbiosis and how this knowledge might help us better understand the pathophysiology of various liver illnesses.

Therapeutic outcomes wide association scan of different antipsychotics in patients with schizophrenia: Randomized clinical trials and multi-ancestry validation.

This study identified discrepant therapeutic outcomes of antipsychotics. A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables. In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (β = -2.17); ziprasidone related to higher risk of increased QT interval (β range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort. Future precision medicine should focus on personalized side-effects.

Predictors of Liver Dysfunction After Transhepatic Arterial Chemo-embolization in Hepatocellular Carcinoma Patients.

Although transhepatic arterial chemo-embolization (TACE) is beneficial for the survival of intermediate stage hepatocellular carcinoma (HCC) patients, its cost is the damage of liver reserve. Liver dysfunction is one of factors associated with TACE refractory status and poor prognosis. The study aims to determine the prevalence and predictors of liver dysfunction in HCC patients after TACE.. Using the ASUS EMR search 3.0 system, the patients with discharge codes "HCC (C22.0)" plus "TACE" were collected since 2016 till 2021 in Taipei Tzu Chi Hospital. Liver reserve was determined by modified albumin-bilirubin (mALBI) grade. The liver dysfunction was defined as mALBI grade migration within 1-3months after TACE.. A total of 220 HCC patients with 314 TACE were found in 5-year duration. Those with TACE-experienced tumors, incomplete laboratory data for mALBI grade and incorrect diagnosis coding were excluded. 91 HCC patients (62 male; mean age 65.86 ± 11.61year-old) were recruited for final analysis. 10 (11%) patients with baseline mALBI grade 3 were excluded. The percentage of mALBI grade migration was 27.2% (22/81) after TACE. Binary logistic regression discovered "up-to-seven out" and "up-to-eleven out" were associated with mALBI grade migration after TACE. In this retrospective study, liver dysfunction occurred in 27.2% of HCC patients after TACE. "Up-to-seven out" and "up-to-eleven out" were predictors for liver dysfunction after TACE, suggesting early switch to systemic therapy to reduce the risk of liver dysfunction for HCC patients with high tumor burden.

Association of Blood Mercury Level with Liver Enzymes in Korean Adults: An Analysis of 2015–2017 Korean National Environmental Health Survey

Increased liver enzymes as a result of exposure to mercury and their toxic effects are not well understood in Korea at the population level. The effect of blood mercury concentration on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated after adjusting for sex, age, obesity, alcohol consumption habit, smoking, and exercise parameters in 3712 adults. The risk of abnormal liver function was measured using a multiple logistic regression analysis. Blood mercury concentration was divided into quartiles, and liver enzyme levels were compared for each quartile. ALT and AST levels were 10-20% higher in the second, third, and fourth quartiles compared to the first quartile. The risk of liver dysfunction or elevated liver enzymes was significantly higher in the second, third, and fourth quartiles than in the first quartile. As blood mercury levels increased, liver enzymes and mercury-induced hepatotoxicity increased. The increase in liver enzymes caused by mercury was more pronounced in the low-mercury concentration range. To reduce the long-standing problem of abnormal liver enzymes and liver function in Korea and other similar settings, it is important to decrease exposure to mercury through effective implementation of specific health and environmental strategies.

Hepatic benefits of sodium-glucose cotransporter 2 inhibitors in liver disorders.

Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed.

Risk of liver dysfunction and non-alcoholic fatty liver diseases in people with hidradenitis suppurativa: A systematic review and meta-analysis of real-world evidences.

To date, evidences with high evidence-level evaluating the association between liver diseases and hidradenitis suppurativa was lacking. Given that inconsistency exists in some of the previous observational studies, evaluating the prevalence of liver diseases in HS patients could potentially serve as a reference of future guidelines for HS comorbidity screening. The aim of the current study was to evaluate potential association between hidradenitis suppurativa and liver diseases and provide integrated evidences. A search in PubMed, Web of Science and Embase based on the syntaxes ''hidradenitis suppurativa'' or ''acne inversa'' with "comorbidities", "liver diseases", "fatty liver" or "hepatitis" was performed. Observational studies evaluating epidemiological association between hidradenitis suppurativa and the risk of all liver diseases, including specific diseases as non-alcoholic fatty liver disease, hepatitis B, hepatitis C were targeted to be extracted in this systematic review and meta-analysis. Within the initial 702 records, there were finally 8 real-world observational studies extracted. Results suggest that patients with HS are associated with all liver diseases (OR= 1.50; 95% CI, 1.27, 1.76), non-alcoholic fatty liver disease (OR= 1.78; 95% CI, 1.28, 2.48) and hepatitis B (OR=1.48; 95% CI, 1.12, 1.94), but not hepatitis C (OR= 1.27; 95% CI, 0.78, 2.07). HS patients were associated with significantly increased risk of liver diseases, especially the risk of non-alcoholic fatty liver disease and hepatitis B. Clinicians should be alert to the clinical relationship while caring people with hidradenitis suppurativa and the screening of liver function should be recommended to HS patients. https://www.crd.york.ac.uk/prospero/, identifier CRD42022296034.

Omicron infections profile and vaccination status among 1881 liver transplant recipients: a multi-centre retrospective cohort

ABSTRACT A wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.

A prediction model for COVID-19 liver dysfunction in patients with normal hepatic biochemical parameters.

Coronavirus disease 2019 (COVID-19) patients with liver dysfunction (LD) have a higher chance of developing severe and critical disease. The routine hepatic biochemical parameters ALT, AST, GGT, and TBIL have limitations in reflecting COVID-19-related LD. In this study, we performed proteomic analysis on 397 serum samples from 98 COVID-19 patients to identify new biomarkers for LD. We then established 19 simple machine learning models using proteomic measurements and clinical variables to predict LD in a development cohort of 74 COVID-19 patients with normal hepatic biochemical parameters. The model based on the biomarker ANGL3 and sex (AS) exhibited the best discrimination (time-dependent AUCs: 0.60-0.80), calibration, and net benefit in the development cohort, and the accuracy of this model was 69.0-73.8% in an independent cohort. The AS model exhibits great potential in supporting optimization of therapeutic strategies for COVID-19 patients with a high risk of LD. This model is publicly available at https://xixihospital-liufang.shinyapps.io/DynNomapp/.

Heavy metals exposure is associated with early liver dysfunction among rural residents aged 40-75 years in southwest China.

Heavy metals exposure has been associated with liver dysfunction in recent reports, while the hepatoxicity of lead (Pb) and cadmium (Cd) has been well established. However, the combined effects of multi-metal in real-world scenario on liver dysfunction are still unclear. This cross-sectional study examined associations between 10 biomarkers of early liver injury and multiple heavy metals levels. The levels of heavy metals/metalloid (magnesium [Mg], calcium [Ca], iron [Fe], zinc [Zn], arsenic [As], Cd, copper [Cu], and Pb) were measured in blood and urinary sample collected from 725 participants in a Cd-polluted area and an unpolluted area in southwest China. The early liver dysfunction biomarkers included the liver enzymes (ALT, ALP, AST, and GGT), proteins (TP, ALB, and GLO), and bilirubin (TBIL, DBIL, and IBIL). Confounder-adjusted beta coefficients were determined using multiple linear regression model analysis for the group-classified and gender-classified samples. Our results showed that blood Fe, Cd, and Cu levels were found to be positively related to elevated ALT levels and blood Cu was positively associated with AST levels in the Cd-polluted area, while the highest blood Zn quartile in the polluted area and blood Mg quartile in the unpolluted area were associated with lower ALT levels. Our finding implies that industrial pollution results in heavy metals of Cd and Pb exposure and effects of Fe, Cd, Cu, and Pb in the Cd-polluted area may be the main contributors to increase the risk of liver dysfunction while Zn in the Cd-polluted area and Mg in the unpolluted area may be the protective factors.

Surveillance of Liver Function in Uveitis with or without Chronic HBV Infection

Introduction: Immunosuppressive therapy for uveitis may cause liver damage. Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. Results: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80–213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79–6.99; p value = 2.8 × 10⁻⁴) and in IPPU (aHR, 3.80; 95% CI, 1.61–9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94–10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). Conclusion: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease.

Background/AimsLittle is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy.MethodsThis retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form.ResultsOverall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis.ConclusionsLiver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

Estimating Prevalence of Hepatitis B Virus Coinfection Among Adults With Tuberculosis: A Systematic Review With Meta-analysis.

While patients with hepatitis B virus (HBV) infection and tuberculosis (TB) have similar risk factors, little is known regarding the prevalence of HBV and TB coinfection. We aim to evaluate the prevalence of HBV among patients with TB across world regions. We systematically reviewed the literature using PubMed from inception through September 1, 2019, to identify studies that provided data to calculate HBV coinfection prevalence among adults with TB infection. Prevalence estimates of HBV coinfection among TB patients were stratified by world regions and calculated using meta-analyses with random-effects models. A total of 36 studies met inclusion criteria (4 from the Africa region, 6 from the Americas region, 5 from the Eastern Mediterranean region, 2 from European region, 6 from Southeast Asia region, and 13 from the Western Pacific region). On meta-analysis, overall pooled HBV coinfection prevalence among TB patients was 7.1%, but varied by world region. Region-specific pooled HBV prevalence among TB patients was highest in Africa region [11.4%, 95% confidence interval (CI): 3.45-19.31] and Western Pacific region (10.8%, 95% CI: 8.68-12.84), and was lowest in the Americas (2.2%, 95% CI: 0.78-3.53). Sensitivity analyses yielded similar HBV prevalence estimates across world regions. In this meta-analysis, we observed HBV coinfection prevalence among TB patients to be 38% to 450% higher than published estimates from the Polaris group of region-specific overall HBV prevalence. Timely identification of HBV infection among TB patients will improve patient outcomes by allowing for closer clinical monitoring and management, which may reduce the risk of liver dysfunction and liver failure related to TB treatment.

Validation of the APRI+ALBI smart phone application for preoperative risk assessment after liver resection in a routine clinical setting

Presenter: David Pereyra MD | Mayo Clinic, Rochester Background: Liver surgery obtains the risk of development of postoperative liver dysfunction (LD) and associated increased morbidity and mortality. In order to mitigate the individual risk for adverse postoperative outcome, predictive markers and scores have been developed. In this context, APRI and ALBI, both based on routine laboratory parameters, and their summative conjunction were previously established as predictive markers for postoperative LD in patients undergoing liver resection after neoadjuvant chemotherapy, as well as in a set of more than 12,000 patients in the NSQUIP database. Here, we aimed to validate APRI+ALBI and our Smart phone application system in a routine clinical set of patients undergoing liver surgery. Methods: We identified 160 patients with available data on preoperative albumin, bilirubin, aspartate aminotransferase and platelet count and postoperative outcome. APRI and ALBI were calculated and prognostic value for postoperative outcome was evaluated. Results: Using receiver operating curve analysis, APRI+ALBI was found to be superior to APRI alone or ALBI alone in prediction of postoperative LD (area under the curve [AUC]=0.717, AUC=0.669, AUC=0.691, respectively). Further, APRI+ALBI was superior to parameters of indocyanine green clearance (plasma disappearance rate: AUC=0.628, retention rate at 15 minutes: AUC=0.669). A preoperative cut-off at -2.46 was able to stratify patients at risk for postoperative LD (6.1% vs 18.0%, p=0.017), morbidity (32.7% vs 63.9%, p<0.001), severe morbidity (11.2% vs 34.4%, p<0.001), and mortality within 90 postoperative days (1.0% vs 8.5%, p=0.028). Utilizing our previously established smart phones application, we were able to validate appropriate classification patients in individual risk groups according to their preoperative APRI/ALBI score. Conclusion: Here, we validate APRI+ALBI as a predictive marker for postoperative adverse outcome in a clinical routine set of patients undergoing liver resection. The detection of multiple with pathophysiological processes , such as for example chemotherapy associated liver injury but also alcoholic liver disease, by the APRI/ALBI score, allowed prediction of outcome after liver resection in an routine clinical setting. Applying this twice validated marker based on routine laboratory parameters allows estimation of individual patient risk prior to liver resection and might ultimately reduce occurrence of postoperative complications. A specific and gradual risk assessment seems to be possible using the APRI/ALBI smart phone application in a routine clinical setting. Until more specific markers are available, this application represents a valuable tool to assess individualized patients risk for postoperative outcome based on routine laboratory parameters.

Von Willebrand factor antigen as a versatile preoperative marker in patients undergoing liver resection for hepatocellular carcinoma

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Risk evaluation in patients with hepatocellular carcinoma (HCC) prior to liver resection is an ongoing debate in the field, as long-term outcome is affected by an increased risk for LD and early disease recurrence. Currently available predictors are costly, not broadly available and lack predictive accuracy. Recently, vWF-Ag was established as a marker for postoperative LD. Due to its pleiotropic associations with components of HCC pathology vWF-Ag was further investigated in a variety of malignant diseases. This study aimed to compare routinely available parameters of risk assessment in HCC patients prior to liver resection and investigate the role of von Willebrand factor antigen (vWF-Ag) as a biomarker for postoperative liver dysfunction (LD), disease recurrence and long-term overall survival (OS). Methods: A total of 72 patients suffering from HCC was included out of a prospective trial cohort investigating the predictive potential of vWF-Ag for immediate outcome after liver resection in 223 patients (ClinicalTrials.gov-Identifier:NCT02118545). Patients clinical course was documented and they were followed up for disease recurrence and OS after discharge. Results: Upon logistic regression only vWF-Ag, volumentric assessment of future liver remnant (FLR) and measures of indocyanine green clearance (ICG-C) were able to predict patients risk for development of LD. In direct comparison using ROC-analysis, vWF-Ag was found to be comparable to parameters of ICG-C (area under the curve [AUC] = 0.828, vs 0.894 and 0.880) and more accurate than FLR (AUC = 0.756) and hepatic venous pressure gradient (HVPG, AUC = 0.590). Multivariable Cox-regression further revealed an independent association of vWF-Ag with disease free survival (odds ratio [OR] = 1.004, 95% confidence interval [CI] : 1.000-1.008). Ultimately, prediction of OS according to preoperative vWF-Ag was independent from development of postoperative LD, morbidity and disease recurrence. Given the clinical relevance to identify patients that might not benefit from liver resection and better served with other treatment options we defined a high risk cohort that developed LD in 55.6% of the cases (vs. 12.7% in vWF-AgLOW patients, p = 0.002) and had a 50% risk for postoperative mortality within the first postoperative year (vs. 11.7% in vWF-AgLOW patients, p = 0.006). Conclusion: Preopertive vWF-Ag is comparable to or more accurate than costly methods of preoperative risk evaluation, including volumetric estimation of FLR, ICG-C and HVPG measurement. In addition, preoperative vWF-Ag is associated with OS independent of postoperative outcome. The present data stresses the use of vWF-Ag as a broadly available routine laboratory parameter in preoperative risk evaluation for HCC patients and suggests that it might allow to personalize surgical strategy and treatment plan to the individual patient.

Risk of Liver Dysfunction After Left Ventricular Assist Device Implantation

Incident liver dysfunction after left ventricular assist device implantation has been previously associated with adverse outcomes, yet data on perioperative risk markers are sparse. We retrospectively reviewed consecutive patients undergoing continuous-flow left ventricular assist device implant between 2007 and 2017 at a single institution. Perioperative variables were evaluated by univariate modeling and adjusted for false discovery rate. Variables most significantly associated with incident Interagency Registry for Mechanically Assisted Circulatory Support-defined liver dysfunction (INT-LD) were evaluated using logistic regression and optimal cutpoints were defined. One-year survival was evaluated using Kaplan-Meier analysis. We included 359 patients (79% male; mean age 59 ± 13 years; 46% ischemic; 64% destination therapy). Lower right ventricular stroke work index at the time of right heart catheterization, higher right atrial pressure 6 hours after right heart catheterization, higher preoperative total bilirubin, longer cardiopulmonary bypass time, and greater volume of intraoperative ultrafiltration were most strongly associated with incident INT-LD (adjusted P < .01 for each). Initial right ventricular stroke work index less than 460 mm Hg∗mL/m2 (odds ratio [OR] 4.6; 95% confidence interval [CI], 2.3 to 9.4), 6-hour right heart catheterization 14 mm Hg or greater (OR 4.3; 95% CI, 2.1 to 8.8), cardiopulmonary bypass time longer than 137 minutes (OR 3.3; 95% CI, 1.8 to 6.2; P < .01 for all), ultrafiltration more than 2.95 L (OR 3.7; 95% CI, 2 to 6.8), and total bilirubin greater than 1.4 mg/dL (OR 2.7; 95% CI, 1.4 to 5) were each strongly associated with risk of INT-LD, which was associated with decreased unadjusted 1-year survival (P < .001). Right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration were each more strongly associated with elevated risk of INT-LD after left ventricular assist device implant than total bilirubin. Therefore, optimization of right ventricular hemodynamics and minimizing cardiopulmonary bypass time and ultrafiltration could potentially reduce the risk of liver dysfunction, but these observations require prospective validation.

Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma.

To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy. SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance. A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis. The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS. The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.