Etiology Of Liver Disease Research Articles

Defining an approach for therapeutic strategies in metabolic dysfunction-associated steatotic liver disease after liver transplantation.

Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction-associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction-associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.

Diagnosis and Treatment of Liver Disease: Current Trends and Future Directions.

This narrative review delves into the intricate landscape of liver diseases, providing a comprehensive background of the diverse conditions that afflict this vital organ. Liver diseases, ranging from viral hepatitis and non-alcoholic fatty liver disease (NAFLD) to cirrhosis and hepatocellular carcinoma (HCC), pose significant global health challenges. Understanding these diseases' multifaceted origins and progression is pivotal for developing effective diagnostic and therapeutic strategies. The epidemiology and etiology of liver diseases emphasize the global impact of viral hepatitis, with hepatitis B and C as significant contributors. Concurrently, the rising prevalence of NAFLD, linked to lifestyle factors and metabolic syndrome, underscores the intricate relationship between modern living and liver health. Chronic liver diseases often evolve insidiously, progressing from inflammation to fibrosis and, ultimately, to cirrhosis - a stage characterized by irreversible scarring and compromised function. The heightened risk of HCC in advanced liver disease stages further underscores the urgency of effective diagnostic and therapeutic interventions. The evolving landscape of non-invasive diagnostic tools is explored for their role in enabling early detection and accurate staging of liver diseases. In the realm of treatment, there is a continuous transition toward personalized medicine, customized to suit the unique profiles of individual patients. This shift encompasses a broad spectrum, ranging from personalized pharmacological interventions to lifestyle modifications and surgical options. Delving into innovative therapies, such as gene editing and immunomodulation, offers a glimpse into the promising future directions that have the potential to redefine the landscape of liver disease diagnosis and treatment.

Lipid disorders before and after successful liver transplantation.

Liver transplantation (LTx) is the only successful treatment for end-stage liver disease. The results of liver transplantation depend not only on graft survival but may be also affected by superimposed cardiovascular morbidities. The aim of this retrospective study was to assess the prevalence of lipid disorders as one of the important cardiovascular risk factors in patients before and after successful LTx. One hundred eleven patients who underwent liver transplantation because of liver cirrhosis and survived at least 2 years with functioning graft between November 2005 and May 2014 were included in this retrospective analysis. The mean age of the patients at the time of liver transplantation was 49.7±12.2 years. The prevalence of dyslipidemia was assessed before and two years after liver transplantation. This was analyzed in relation to the etiology of liver disease, including alcohol toxicity, viral or autoimmune diseases. The prevalence of hypertriglyceridemia before and after LTx was 13.5% and 40.5%, respectively (P<0.001). Similarly, hypercholesterolemia was noted in 17.1% and 51.4% respectively (P<0.001). The annual incidence of hypertriglyceridemia and hypercholesterolemia during the first two years after LTx was 16.2% and 20.7%, respectively. The prevalence of hypertriglyceridemia (18.5% vs 66.7%, P<0.001) and hypercholesterolemia (29.6% vs 70.0%, P=0.002) was significantly lower in patients with the autoimmune cause of liver cirrhosis in comparison to patients with the alcoholic liver disease. The prevalence of dyslipidemia is increased after liver transplantation. The prevalence of dyslipidemia may be related to the cause of liver injury before LTx.

A comparison between patients with various etiologies of cirrhosis and examination of cardiac risk factors limiting survival to liver transplantation.

Objectives of this retrospective cohort study were to assess differences in patient survival between etiologies of cirrhosis while on the waitlist for liver transplantation (LT), and to identify cardiac risk factors that predict survival failure while on the waitlist for LT. This single-center retrospective cohort design included adult patients who were listed for LT at a tertiary academic hospital with a high-volume liver transplant center. Of the 653 patients listed for LT during the study period, 507 (77.6%) survived to transplant and 146 (22.4%) died or clinically deteriorated prior to transplant. Cumulative incidence of death or clinical deterioration did not differ statistically between patient groups (log rank p=.11). In multivariate analysis, compared to patients with NAFLD, there were no significant differences between patients with alcoholic cirrhosis (HR .95, 95%, CI, .62-1.45), cryptogenic cirrhosis (HR 1.31, 95%, CI, .77-2.23), or hepatitis C cirrhosis (HR 1.12, 95%, CI, .66-1.90). However, higher MELD scores (HR=1.52, 95% CI, 1.12-1.19), severe coronary artery disease (HR=2.09 95% CI, 1.23-3.55), and tricuspid regurgitation (HR=2.62, 95% CI, 1.31-5.26) were independently associated with increased risk for survival failure to LT. The presence of severe coronary artery disease and tricuspid regurgitation at the time of listing for transplant are associated with survival failure while on the LT waitlist across etiologies of liver disease. Diagnostic assessment of coronary and valvular disease should be considered in all patients undergoing evaluation for LT, such as cardiac catheterization and/or stress echocardiogram.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score

BackgroundDiagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). MethodsA multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. ResultsAmong 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. ConclusionsDespite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Characteristics of candidates from the waiting list for liver transplantation in the Republic of Moldova

Abstract: Liver transplantation (LT) is the most efective method of treatment of end-stage liver disease. Due to the low number of effective donors, the number of patients on the waiting list (WL) in the Republic of Moldova continues to increase. We aimed to analyze the particularities of the candidats from waiting list for liver transplantation according to demographic, etiological and clinical data. Materials and methods: In retrospective, observational, descriptive study have been included candidats from the waiting list for LT in period between February 2013 and April 2022. Variables analyzed were: age, gender, MELD-Na score, BMI, etiology of end-stage liver disease, mortality and transplantation rates from the waiting list. Results: 246 patients were included in the waiting list for LT during the baseline period. Only 61 (25%) of these were transplanted. The main indication for liver transplantation was advanced liver disease (ALD) of viral etiology in 80.7%. Males predominated (60.56%), with a mean age of 47.7 ± 9.6 years. The mean follow-up duration of patients was 816,49 days ± 880.405. The mean MELD-Na score at inclusion was 12.22 points. Conclusion: Advanced liver disease of viral etiology is the main indication for inclusion in the waiting list (WL) in our transplant center. These patients have a lower MELD-Na score at inclusion but a higher rate of decompensation and death on the waiting list.

Vaccine-Preventable Illness Leads to Adverse Outcomes in Liver Transplant Recipients.

Liver transplant recipients (LTR) and patients with chronic liver disease (CLD) are at an increased risk of infections. The objective of our study was to assess the incidence, and impact of vaccine preventable illness (VPI) on outcomes in LTR. National Inpatient Sample (NIS) 2016-2020 was used to identify adults (age > 18) hospitalized LTR using ICD-10 codes. Data were collected on patient demographics, hospital characteristics, etiology of liver disease, hepatic decompensations and outcomes. Patients were stratified into two groups based on the presence or absence of VPI. Multivariate logistic regression analysis was performed to identify the association between VPI and outcomes. Out of 170,650 hospitalized LTR, 13.5% of the patients had VPI. The most common VPI was noted to be influenza (10.7%), followed by pneumococcal infection (2.7%). Incidence of mortality (6.9% vs. 1.6%, p < 0.001), ICU admissions (14.3% vs. 3.4%, p < 0.001), and acute kidney injury (AKI) (43.7% vs 37.35%, p < 0.001) was higher in the VPI group. More than 13% of the LT hospitalizations had concomitant VPI. VPI in LTR was associated with worse outcomes. Our data suggests the need to identify factors associated with reduced vaccination rates and identify strategies to improve vaccination rates and responses in these patients.

Outcomes among patients with hepatorenal syndrome based on hospital teaching and transplant status: Analysis of 159 845 hospitalizations.

Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver disease. This study aimed to examine the impact of hospital teaching/transplant status and availability of liver transplantation on survival among hospitalized patients with HRS in the United States. Patients with HRS were identified from the national inpatient sample 2016-2019. Information was collected regarding patient demographics, hospital characteristics, liver disease etiology, presence of liver disease decompensations, Elixhauser comorbidities, and interventions. Patients were classified as being treated at three hospital groups: non-teaching hospitals (NTHs), teaching non-transplant centers (TNTCs), and teaching transplant centers (TTCs). The relationship between hospital teaching/transplant status and in-hospital mortality and transplant-free mortality was examined using multivariable linear and logistic regression analysis. A total of 159,845 patients met the criteria for HRS. Of these, 24% were admitted to NTHs, 50.8% to TNTCs, and 25.2% to TTCs. Admission to a TTC was independently associated with a lower mortality risk compared to admission to non-TTCs (aOR = 0.75, 95% CI: 0.68-0.83, P <0.001). Patients at TTCs had a lower transplant-free mortality risk than those at NTHs (aOR = 0.75, 95% CI: 0.67-0.83, P < 0.001). There was no significant difference in all-cause or transplant-free mortality between TNTCs and NTHs. Patients with HRS admitted to TTCs have higher disease severity, but significantly improved outcomes compared to those admitted to NTHs. These data suggest opportunities for increased disease awareness and education among NTHs and support early referral for liver transplant evaluation among hospitalized patients with HRS.

The rate of biliary adverse events in duct-to-duct living donor liver transplant compared with deceased donor liver transplant

Background and AimsLiving donor liver transplantation (LDLT) allows for decreased listing-to-transplant time in patients with end-stage liver disease (ESLD) but has been noted to be associated with higher rates of biliary adverse events. We aim to assess the adverse events of LDLT and compare to deceased donor liver transplant (DDLT) patients. MethodsWe retrospectively reviewed patients having undergone duct-to-duct anastomosis LDLT at a single center from 2011-2020. Exclusion criteria included pediatric patients and LDLT with Roux-en-Y hepaticojejunostomy. Patients were then matched 1:1 with DDLT. Matching was performed by age, gender, etiology of liver disease, and MELD. Outcomes of interest included incidence of biliary strictures, bile leak, stricture recurrence rate and the number of interventions required for stricture resolution. ResultsFifty patients with LDLT were matched to 50 patients with DDLT. Bile leak occurred in 14 (38%) vs 5 (10%) patients in LDLT and DDLT groups, respectively (p-value 0.001). Biliary strictures occurred in 14(28%) vs 15(30%) patients in LDLT and DDLT groups, respectively (p-value 0.68). There was no difference in the median number of interventions required to resolve the strictures [3 (2-6) vs 4 (3-5), respectively; p-value 0.79]. Three patients in each group had recurrence of strictures after documented resolution. Mortality in both groups were similar [5 (10%) patients in LDLT vs 6(12%) in DDLT (P-value 0.75)]. ConclusionPatients who undergo LDLT were equally as likely to develop anastomotic strictures compared to DDLT. Duct-to-duct anastomosis LDLT should be frequently considered in patients with ESLD with favorable anatomy.

Estado de salud de pacientes con trasplante hepático por enfermedad relacionada con el consumo de alcohol vs. otras etiologías: estudio de cohortes

AimTo study the health status of a group of patients with liver transplantation by alcohol-related disease vs another etiology before and after the transplantation. MethodLongitudinal cohort study of liver transplant patients from November 2019 to July 2022. Adult patients attended in the unit of transplantation of a hospital for a first liver transplant, both elective and urgent, were included. Patients who already had a transplanted organ and those who required liver re-transplantation in the first month after the first transplant were excluded. Sociodemographic and clinical variables, MELDNa, liver frailty index, emotional-behavioral effects of transplantation, level of anxiety and depression were collected. Pearson's chi-square, Student's t, Mann-Whitney U, and Wilcoxon sign tests were used for statistical analysis. ResultsThe sample was n = 67 liver transplant patients with a mean age of 56.37 years, 67.2% being men and 39% due to alcohol-related liver disease. 9% of all included patients were urgent transplants. Alcohol consumption was associated with older age, a high rate of liver frailty, and a non-active work situation. Alcoholic etiology correlated with increased concern during the first six months after liver transplantation. ConclusionThere are differences in the health status between liver transplant patients for alcohol-related liver disease vs other etiology. Nurses must consider the etiology of liver disease to guide care and interventions throughout the transplant process.

Knowledge needs in patients with Liver Disease: a qualitative study

BackgroundKnowledge is essential for patients’ disease management strategies and a critical component of healthcare. The importance of increasing patients level of knowledge has become more widely acknowledge in liver disease management in recent years, but further studies are needed to address patients experiences of unmet knowledge needs to develop appropriate patient education strategies. Therefore, the aim of this study was to explore knowledge needs in patients’ with liver disease of different etiology and severity.MethodsA qualitative study was designed and an inductive method was chosen. Thirty-three patients with liver disease of different etiology and severity were interviewed using a semi-structured interview guide. Content analysis was used as an inspiration to describe and compare patients’ needs for knowledge across disease etiology and severity. The reporting followed consolidated criteria for reporting qualitative research.ResultsThe analysis generated three categories and nine subcategories. In general, the patients described lack of knowledge related to their liver disease, which made it difficult for them to manage their disease. Patients wished to be more involved in care and treatment of the liver disease. However, patients’ had difficulties to assess and understand the importance of the information they received from healthcare professionals. Due to lack of knowledge, patients’ had a misconception of the liver disease. Patients’ had variation in knowledge needs depending on liver disease etiology and severity.ConclusionWithin liver disease management, knowledge of patients’ experiences is vital to meet patients’ knowledge needs and to develop appropriate patient education strategies. Therefore, it is important to ascertain a patient-centered approach to accommodate patients’ individual knowledge needs, involve patients in care and treatment, and insure understanding to strengthen their self-management and give the patients the necessary skills to manage their disease and everyday life.Registration numberOpen Science Framework registration DOI https://doi.org/10.17605/OSF.IO/W28RC.

Global liver transplantation: emerging trends and ethical challenges.

Liver transplant (LT) is the only definitive treatment for end-stage liver disease (ESLD). This review aims to explore current global LT practices, with an emphasis on challenges and disparities that limit access to LT in different regions of the world. A detailed analysis was performed of present-day liver transplant practices throughout the world, including the etiology of liver disease, patient access to transplantation, surgical costs, and ongoing ethical concerns. Annually, only 10% of the patients needing a liver transplant receive an organ. Currently, the USA performs the highest volume of liver transplants worldwide, followed by China and Brazil. In both North America and Europe, nonalcoholic fatty liver disease is becoming the most common indication for LT, compared to hepatitis B and C in most Asian, South American, and African countries. While deceased donor liver transplant remains the most performed type of LT, living donor liver transplant is becoming increasingly popular in some parts of the world where it is often the only option due to a lack of well-developed infrastructure for deceased organ donation. Ethical concerns in liver transplantation fundamentally revolve around the definition of a deceased donor and the exploitation of living donor liver donation systems. Globally, liver transplant practices and outcomes are varied, with differences driven by healthcare policies, inequities in healthcare access, and ethical concerns.

Hepatitis A Vaccination Coverage Among People With Chronic Liver Disease in England (HEALD): Protocol for a Retrospective Cohort Study.

Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally. This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine. We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated. The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group. This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population. PRR1-10.2196/51861.

The evolution of liver transplant program in Pakistan and the challenges ahead

Background and aimThe burden of Liver disease has significant implications on the healthcare infrastructure in Pakistan, with viral hepatitis being the leading etiology of end-stage liver disease. Liver transplant remains the only curative treatment option for end-stage liver disease. A decade ago, the liver transplant facility was almost non-existent for the Pakistani population, and the patients with end-stage liver disease had to travel overseas to receive liver transplantation. Gradually, during the last decade the country has progressed steeply and achieved various milestones in living donor liver transplantation. Various public and private sector hospitals are providing liver transplant services nationwide. The study aimed to describe the evolution and success of living donor liver transplant programs in Pakistan. We will also discuss the current practices involved in donor and recipient selection, factors related to non-existent deceased donor organ programs, and the introduction of innovative strategies to overcome the shortage of donor organ pools. MethodsWe retrospectively analyzed the data of the first 416 living donor liver transplants (LDLTs) performed at PKLI&RC from March 2019 to April 2023. The stepwise approach for the donor and recipient selection process is described in detail, along with the survival outcomes of LDLT at our center. ResultsAmong the 416 living donor liver transplants performed between March 2019 and April 2023. The Hepatitis C virus was the most common etiology (50.5 %) for chronic liver disease. Hepatocellular carcinoma (HCC) was present in 27.9 % of cases. Most donors were offspring of the recipients, with sons accounting for 23 % and daughters for 17.5 % of cases. Only a single (0.24 %) patient had a deceased donor transplant. The annual donor rejection rate was up to 68 % at our center. Nine SWAP transplants were performed to overcome the donor shortage. The Clavien Dindo classification system was used to grade the severity of complications after donor hepatectomy. No donor mortality (grade-5 complication) was observed in our cohort, whereas 1- and 3-year recipient survival rates were 89 % and 88 %, respectively. ConclusionHepatitis C virus remains the most common etiology of chronic liver disease requiring liver transplantation. The major pool of living donations was from first-degree relatives. There was no donor mortality with acceptable 1- and 3-year recipient's survival rates. Living donor liver transplantation is a feasible and safe strategy in regions where cadaveric liver transplant program is limited.

Health status of patients with liver transplantation by alcohol-related disease vs another etiology: A cohort study

AimTo study the health status of a group of patients with liver transplantation by alcohol-related disease vs another etiology before and after the transplantation. MethodLongitudinal cohort study of liver transplant patients from November 2019 to July 2022. Adult patients attended in the unit of transplantation of a hospital for a first liver transplant, both elective and urgent, were included. Patients who already had a transplanted organ and those who required liver re-transplantation in the first month after the first transplant were excluded. Sociodemographic and clinical variables, MELDNa, liver frailty index, emotional–behavioral effects of transplantation, level of anxiety and depression were collected. Pearson’s chi-square, Student’s t, Mann–Whitney U, and Wilcoxon sign tests were used for statistical analysis. ResultsThe sample was n = 67 liver transplant patients with a mean age of 56.37 years, 67.2% being men and 39% due to alcohol-related liver disease. 9% of all included patients were urgent transplants. Alcohol consumption was associated with older age, a high rate of liver frailty, and a non-active work situation. Alcoholic etiology correlated with increased concern during the first six months after liver transplantation. ConclusionThere are differences in the health status between liver transplant patients for alcohol-related liver disease vs other etiology. Nurses must consider the etiology of liver disease to guide care and interventions throughout the transplant process.

Changing Prevalence of Medication Use in People with Cirrhosis: A Retrospective Cohort Study Using Pharmaceutical Benefits Scheme Data.

Safe and appropriate use of medicines is essential to improve health outcomes in cirrhosis. However, little is known about the number and type of medicines dispensed to people with cirrhosis in Australia, as this predominantly occurs in the community. We aimed to characterise the prescriptions dispensed to people with cirrhosis and explore changes in the use of medication groups over time. Pharmaceutical Benefits Scheme data between 1 January 2016 and 30 June 2020 was extracted for consenting CirCare participants (multi-site, prospective, observational study). Prescriptions dispensed from cirrhosis diagnosis until liver transplant or death were included. Safety classifications for dispensed medicines were defined using published evidence-based recommendations. The pattern of medication use was analysed in 6-monthly time intervals. Generalised estimating equations models were used to estimate the change in consumption of medicines over time. Five hundred twenty-two patients (mean age 60years, 70% male, 34% decompensated at recruitment) were dispensed 89,615 prescriptions during the follow-up period, representing a median of 136 [interquartile range (IQR) 62-237] prescriptions and a median of 16 (IQR 11-23) unique medicines per patient (total n=9306 medicines). The most commonly used medicines were proton pump inhibitors (PPIs) (dispensed at least once to 73% of patients), opioids (68%) and antibiotics (89%). Polypharmacy was prevalent, with 59-69% of observed participants in each time period dispensed five or more unique medicines. Prescription medication use increased over time (p<0.001) independently of age, comorbidity burden and liver disease aetiology. The likelihood of taking PPIs, opioids, antidepressants and inhaled medicines also increased with each successive time period. Use of angiotensin therapies, metformin and statins differed over time between patients with compensated versus decompensated cirrhosis. General practitioners prescribed 69% of dispensed medicines, including a higher proportion of 'unsafe' and 'safety unknown' medicines compared with consultants/specialists (p<0.001). Polypharmacy is common in people with cirrhosis and some medication groups may be overused. Pharmacovigilance is required and future medication safety efforts should target high-risk prescribing practices and promote medication rationalisation in the community.

Early liver transplantation for severe alcohol-associated hepatitis: A single-center experience

Liver transplantation (LT) is life-saving for patients with alcohol-associated liver disease (ALD) and severe alcohol-associated hepatitis (SAH). In this retrospective analysis of deceased donor LT from 10/2018 to 4/2022, patients were subdivided into those with ALD with <6 months (M) or >6 M sobriety vs. non-ALD etiologies of liver disease. Patients with <6 M sobriety were further stratified into those meeting the NIAAA criteria for SAH. Of the 367 LT, ALD comprised 171(47 %) of all LT; 85(50 %) had <6 M sobriety. Comparing those with ALD with <6 M to >6 M sobriety and other non-ALD etiologies, those with <6 M were younger (mean age 46 vs. 54 and 56 years; p < .001), had higher MELD (36 vs. 26 and 23; p < .001), and on the list fewer days (14 vs. 83 and 168; p < .001) while there were no differences in gender or length of stay following LT. Of those with <6 M sobriety, 41 met the NIAAA definition of SAH: mean age 43, 42 % female, 0 % AA, mean MELD of 37, mean days of abstinence 58d prior to LT with 29 % prior ALD rehabilitation, 58 % failed steroids, and were listed for 7 days prior to LT. The 1-year survival was similar in all groups with 90 % in SAH, 93 % in <6 M, 93 % in >6 M, and 94 % in those receiving LT for all other causes. While 24 % with SAH had an alcohol slip following LT, only 4 % had a return to harmful drinking. Our single center experience shows LT for those with AUD and <6 M of sobriety and specifically SAH have excellent 1-yr survival similar to those with AUD >6 M sobriety and other etiologies with a low rate of return to harmful drinking.

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors. We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk. A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p=0.04), cirrhosis (HR 3.17, p=0.01), and AIH/PSC variant syndrome (HR 5.18, p=0.007) at baseline were independent risk factors for HCC development. HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome. The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors.

Advanced Hepatocellular Carcinoma Patients with Poor Access to Systemic Therapy Treated with Definitive Stereotactic Body Radiation Therapy: A Single-Institution Experience in Latin America

The standard treatment for patients with advanced hepatocellular carcinoma (aHCC) is systemic therapy with or without stereotactic body radiation therapy (SBRT). We present our experience using SBRT as a definitive treatment for aHCC patients with poor access to systemic therapy. We performed a retrospective review of patients treated with SBRT at the largest institution in Santiago, Chile between June 2016 and September 2022. All patients were deemed unsuitable for another locoregional treatment by the tumor board. We registered demographic, clinical and treatment characteristics. Additionally, treatment response rates using mRECIST criteria, overall survival (OS), local control (LC) and treatment toxicity were reported. We performed a multivariate analysis of variables using Cox proportion hazard ratio for OS and logistic regression for LC. A total of 59 patients were included (41 males and 18 females; median age: 70 years [range: 38 - 85 years]), with a total of 63 treatment courses. Most common etiologies of chronic liver disease were nonalcoholic fatty liver disease (23%) and chronic alcohol consumption (20%). Most patients were classified as Child-Pugh Class A (80%). Barcelona Clinic Liver Cancer (BCLC) stage was 2%, 11%, 49% and 38% for stages 0, A, B and C, respectively, while macrovascular invasion was present in 10 (18%) of patients. Forty-six patients (73%) had been subjected to prior locoregional therapy and only 5 patients (8,5%) received systemic therapy after SBRT. Median tumor size was 7 cm. (range: 0.95 - 32 cm). Median radiation dose was 40 Gy (range: 26.5 - 50 Gy) in 5 fractions. Evaluation of radiological response was performed in 46 patients (79%), with complete response, partial response, stable disease and progressive disease in 41%, 43%, 7% and 9% of the cohort, respectively. With a median follow-up of 9 months (range: 0 - 58), 34 patients (58%) died with a median OS of 10.8 months (range: 0 - 28 months). At 12 months, OS was 65.2% (95% CI: 50.9 - 76.3) and at 24 months was 40.7% (95% CI: 26.2 - 54.6) In multivariate analysis tumor size (as a continuous variable) was the only significant variable for LC (OR 2.9 [CI 1.1 - 5.3; p 0.03]) and for OS (HR 3.4 [CI 1.3 - 6.7; p< 0.01]). Four patients developed grade 3 toxicity (3 thrombocytopenia and 1 duodenal ulcer) and only two treatments were suspended definitively. Despite systemic therapy is the standard treatment for aHCC, a minor proportion of patients received the standard of care. SBRT is safe, feasible and a well-tolerated treatment option for aHCC with good clinical outcomes. To our knowledge, this is the first cohort reported of patients with aHCC treated with SBRT in Latin America.

The Trends in Health Care Utilization and Costs Associated With Primary Liver Cancer: An Analysis of United States Hospitals Between 2016 and 2019.

Primary liver cancer (PLC) has placed an increasing economic and resource burden on the health care system of the United States. We attempted to quantify its epidemiology and associated costs using a national inpatient database. Hospital discharge and insurance claims data from the National Inpatient Sample were used to conduct this analysis. Patients diagnosed with PLC (hepatocellular carcinoma or cholangiocarcinoma) were included in the study population, which was then stratified using patient demographics, comorbidities, degree of cancer spread, liver disease complications, and other descriptors. Trends were analyzed via regression curves for each of these strata from the years 2016 to 2019, with special attention to patterns in hospitalization incidence, inpatient mortality rate, total costs, and average per-capita costs. The resulting curves were evaluated using goodness-of-fit statistics and P -values. Aggregate hospitalization incidence, inpatient mortality rates, and total costs were found to significantly increase throughout the study period ( P =0.002, 0.002, and 0.02, respectively). Relative to their demographic counterparts, males, White Americans, and those older than 65 years of age contributed the largest proportions of total costs. These population segments also experienced significant increases in total expenditure ( P =0.04, 0.03, and 0.02, respectively). Admissions deemed to have multiple comorbidities were associated with progressively higher total costs throughout the study period ( P =0.01). Of the categorized underlying liver diseases, only admissions diagnosed with alcoholic liver disease or nonalcoholic fatty liver disease saw significantly increasing total costs ( P =0.006 and 0.01), although hepatitis C was found to be the largest contributor to total expenses. From 2016 to 2019, total costs, admission incidence, and inpatient mortality rates associated with PLC hospitalization increased. Strata-specific findings may be reflective of demographic shifts in the PLC patient populations, as well as changes in underlying chronic liver disease etiologies.