Taiwan's national strategies and actions toward HCV elimination before 2025

In 1990, the seroprevalence of antibody against hepatitis C virus (anti- HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been well-documented by REVEL-HCV study. A national program of antiviral therapy for chronic viral hepatitis was launched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO's 2030 goals in 2025. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. There are triple focuses of hepatitis C elimination in Taiwan including (1) therapy spearheads prevention, (2) screening supports therapy, and (3) prevention secures outcome. A total of US$1.7 billion will be allocated from 2017 to 2025 for the elimination of HCV. The coverage of HCV screening and treatment has been increasing significantly since 2017. The HCV screening coverage was almost 100% for dialytic patients, 96% for HIV-infected patients, 65% for patients under opioid substitution treatment, 63% for patients in the pre-end-stage renal disease care program, 57% for patients in the early chronic kidney disease care program, 52% for patients in diabetes care program, 39% for prisoners, and 38% for adults aged 45-79 years old in the general population by April 30, 2020. The budget to cover the cost of DAA increased from US$101 million in 2017 to US$219 million in 2019. The number of chronic hepatitis C patients receiving DAA therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,806 in 2019. However, the number of DAA-treated CHC patients reduced to 36,159 in 2020 and 20,559 in 2021 due to the COVID-19 pandemic. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, over 98.6% after 2019. It is expected that Taiwan will achieve WHO's HCV elimination goal by 2025.

Changes in Disease Etiology of Deceased Donor Liver Transplantations Following Acuity Circles Policy Implementation

Introduction: The Acuity Circles (AC) allocation policy was implemented on February 4, 2020, with the primary intent of reducing disparities in access to deceased donor liver transplants (DDLTs). Overall, it has been successful at achieving this goal. However, changes in end-stage liver disease etiology following the policy change have not been well-characterized. Our goal was to understand how primary etiology of disease in DDLTs has changed since implementation of AC. Method(s): Data from the Organ Procurement Transplantation Network (OPTN) and United Network of Organ Sharing (UNOS) were analyzed to compare the primary classified etiologies of liver disease for DDLTs overall and based on allocation Model-for-end-stage-liver-disease (aMELD) categories used for AC sharing: aMELD>=37, aMELD 33-36, aMELD 29-32, aMELD 15-28, and aMELD<=14 DDLTs. Time was divided into four equivalent "eras" of 256 days duration by date of transplantation: 1) 9/10/18-5/23/19 (Era 1);2) 5/24/19-2/3/20 (Era 2);3) 2/4/20-10/16/20 (Era 3);and 4) 10/17/20-6/29/21 (Era 4). Result(s): The percentage of all DDLTs for alcohol-related liver disease (ARLD) increased from 32.3% pre-AC to 38.7% of DDLTs post AC. This was met with a corresponding decrease in the relative percentage of DDLTs related to Hepatitis C Virus (from 17.0% of DDLTs pre-AC to 12.2% post-AC), with the relative differences of other etiologies being a less than 1% difference pre- vs post- AC. There is a consistent increase in the share of DDLTs due to ARLD across each Era. The rise in adult DDLTs for ARLD was most pronounced among aMELD >=37 recipients, although similar trends were seen among aMELD 33-36 and aMELD 29-32 groups, but not aMELD 15-28 and aMELD <=14 groups. The median age of adult DDLTs for ARLD decreased consistently over time for the aMELD >=37 group, but not for the aMELD 33-36 and aMELD 29-32 groups. (Figure) (Table) Conclusion(s): Following implementation of AC, there was a relative increase in DDLTs due to ARLD. The younger age and high aMELD scores of these patients suggests these may be largely among patients with acute alcoholic hepatitis. This would align with published data on the overall increase in liver transplantation due to ARLD during the COVID-19 pandemic. (Figure Presented).

2022 CAS Virtual Annual Meeting

The proceedings contain 63 papers. The topics discussed include: a retrospective study to optimize post-anesthetic recovery time after ambulatory lower limb orthopedic procedures at a tertiary care hospital in Canada;a virtual airway evaluation as good as the real thing?;airway management during in hospital cardiac arrest by a consultant led airway management team during the COVID-19 pandemic: a prospective and retrospective quality assurance project;prevention of cautery induced airway fire using saline filled endotracheal tube cuffs: a study in a trachea airway fire model;smart phone assisted retrograde illumination versus conventional laryngoscope illumination for orotracheal intubation: a prospective comparative trial;time to single lung isolation in massive pulmonary hemorrhage simulation using a novel bronchial blocker and traditional techniques;cannabinoid type 2 receptor activation ameliorates acute lung injury induced systemic inflammation;bleeding in patients with end-stage liver disease undergoing liver transplantation and fibrinogen level: a cohort study;endovascular Vena Cavae occlusion in right anterior mini-thoracoscopic approach for tricuspid valve in patients with previous cardiac surgery;and mesenchymal stem cell extracellular vesicles as a novel, regenerative nanotherapeutic for myocardial infarction: a preclinical systematic review.

Pre-existing chronic liver disease is associated with poor outcome in patients with SARS-CoV2 infection

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Cirrhosis is characterized by immune dysregulation, leading to concerns that these patients may be at increased risk of complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-sixfold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. An international European registry study included 756 patients with chronic liver disease from 29 countries reports high mortality in patients with cirrhosis (32%). Data of 228 patients collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 (APCOLIS study) showed that SARSCoV- 2 infection produces acute liver injury in 43% of CLD patients without cirrhosis. Additionally, 20% of compensated cirrhosis patients develop either ACLF or acute decompensation. In decompensated cirrhotics, the liver injury was progressive in 57% of patients, with 43% mortality. Patients with CLD and associated diabetes and obesity had a worse outcome. Liver related complications were seen in nearly half of the decompensated cirrhotics, which were of greater severity and with higher mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. In a subsequent study of 532 patients from 17 Asian countries was obtained with 121 cases of cirrhosis. An APCOLIS risk score was developed, which included presence of comorbidity, low platelet count, AKI, HE and respiratory failure predicts poor outcome and an APCOLIS score of 34 gave a sensitivity and specificity of 79.3%, PPV of 54.8% and NPV of 92.4% and predicted higher mortality (54.8% vs 7.6%, OR = 14.3 [95 CI 5.3-41.2], p<0.001) in cirrhosis patients with Covid-19. The APCOLIS score is helpful in triaging and prognostication of cirrhotics with Coivd-19. The impact of COVID-19 on patients with cirrhosis due to non-alcoholic fatty liver disease (NASH-CLD) was separately studied in 177 NASH-CLD patients. Obese patients with diabetes and hypertension had a higher prevalence of symptomatic COVID. Presence of diabetes [HR 2.27], fraility [HR 2.68], leucocyte counts [HR 1.69] and COVID-19 were independent predictors of worsening liver functions in patients with NASH-CLD. Severity of Covid in Cirrhosis could also be assessed by measuring ICAM1 the Intercellular Adhesion Molecule, an indicator of Endothelial Injury Marker. in Cirrhosis with Covid 19 Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir are found to be safe in limited studies in a patient with cirrhosis and COVID-19. And is safe in cirrhosis patients. However, flare of AIH has been reported in AIH patients. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic cause severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Indications and results in cholestatic liver disease - PSC, SSC, PBC.

Primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and primary biliary cholangitis (PBC) are impor-tant indications for liver transplantation. An emerging indication for liver transplantation in selected cases is SSC after severe COVID-19 infection. The clinical presenta-tion of these cholestatic diseases is highly heterogeneous - from asymptomatic and mild elevations of liver enzymes to severe disease-specific complications like recurrent cholangitis or severe bone disorder to de-compensated liver cirrhosis. Such disease-specific clinical complications, disease-spe-cific scores, as well as the MELD score, need to be considered when selecting patients for liver transplantation.Copyright © 2023 Dustri-Verlag Dr. K. Feistle.

Solid organ graft-versus-host disease in a recipient of a COVID-19 positive liver graft

A 66-year-old male with end-stage liver disease (ESLD) secondary to non-alcoholic fatty liver disease (NAFLD), complicated by hepatocellular carcinoma (HCC), underwent deceased donor liver transplantation from a Coronavirus disease 2019 (COVID-19) positive donor. He presented a month later with fever, diarrhea and pancytopenia which led to hospitalization. The hospital course was notable for respiratory failure, attributed to invasive aspergillosis, as well as a diffuse rash. A bone marrow biopsy revealed hypocellular marrow without specific findings. In the following days, laboratory parameters raised concern for secondary hemophagocytic lymphohistiocytosis (HLH). Clinical concern also grew for solid organ transplant graft-versus-host-disease (SOT-GVHD) based on repeat marrow biopsy with elevated donor-derived CD3+ T cells on chimerism. After, a multidisciplinary discussion, the patient was started on ruxolitinib, in addition to high dose steroids, to address both SOT-GVHD and secondary HLH. Patient developed symptoms concerning for hemorrhagic stroke and was transitioned to comfort care. Although GVHD has been studied extensively in hematopoietic stem cell transplant (HSCT) patients, it is a rare entity in SOT with a lack of guidelines for management. Additionally, whether COVID-19 may play a role in development of SOT-GVDH has not been explored.Copyright © 2023 The Authors

Treatment of COVID-19 with special consideration of liver diseases.

Patients with chronic liver disease (CLD), especially cirrhosis, and immunosuppressed post-liver transplant patients generally appear to be at increased risk of infection, resulting in increased mortality. This is also evident in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, where patients with cirrhosis in particular are at high risk for coronavirus disease 2019 (COVID-19). Prevention and treatment of SARS-CoV-2 infection are therefore important measures to protect this vulnerable group of patients from the consequences of COVID-19. The recent SARS-CoV-2 pandemic has led to exceptionally rapid development of vaccines, prophylactic and therapeutic antibodies, as well as testing of new drugs and drugs already approved for other indications. In this article, we summarize therapeutic approaches with special consideration of patients with chronic liver disease and patients after liver transplantation.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Mortality on Liver Transplant Waiting List: Analysis of a Transplant Center in Colombia

Introduction and Objectives: Cirrhosis and acute liver failure have a high mortality rate and liver transplantation is the only treatment that has shown improvement in the survival of these patients, being 90% in the first year after transplantation and 80% in five years. Currently, in our center there are 95 patients on the liver transplant waiting list, being the largest in the country. The availability of an organ is of key importance and is directly related to the morbidity and mortality of our patients. This study aimed to determine direct and indirect variables that affect mortality on the waiting list in our transplant center. Material(s) and Method(s): We did a retrospective observational study in which we reviewed the clinical charts of the 116 patients who died in the liver transplant list between 2015 and 2021. We described the stage of cirrhosis, its complications and the cause of death. For the analysis of the results, we performed a statistical description. Result(s): Between 2015 and 2021, 116 patients died on the liver transplant waiting list. The cause of cirrhosis was autoimmune disease in 42%of the patients, 75% were CHILD C and 39.7% had MELD >25. The main cause of death was an infection, and the main complications of cirrhosis were ascites (84.5%), encephalopathy (59.5%) and variceal hemorrhage (39.7%). Between 2020 and 2021, COVID-19 infection was documented in 16.7% of deceased patients. Conclusion(s): Infection in patients on the waiting list is the main cause of death before transplantation. It has been documented in the literature that one-year mortality, according to the Meld score, is 30% and 50% for scores of 20-29 and 30-39, respectively. Because of this reason, liver transplantation is the only alternative to impact the survival of these patients. The pandemic contingency affected the care of patients with terminal liver disease, reducing the number of transplants performed because of the lower donation rate. Being pioneers in Colombia of living donor transplantation, it was possible to mitigate the low availability of organs during the Covid-19 pandemic, and in 2020 -2021, 38% of the transplants performed in our center were from a living donor.Copyright © 2023

Infection prevention and control programme and COVID-19 measures: Effects on hospital-acquired infections in patients with cirrhosis.

Background & Aims: Bacterial infections affect survival of patients with cirrhosis. Hospital-acquired bacterial infections present a growing healthcare problem because of the increasing prevalence of multidrug-resistant organisms. This study aimed to investigate the impact of an infection prevention and control programme and coronavirus disease 2019 (COVID-19) measures on the incidence of hospital-acquired infections and a set of secondary outcomes, including the prevalence of multidrug-resistant organisms, empiric antibiotic treatment failure, and development of septic states in patients with cirrhosis. Methods: The infection prevention and control programme was a complex strategy based on antimicrobial stewardship and the reduction of patient's exposure to risk factors. The COVID-19 measures presented further behavioural and hygiene restrictions imposed by the Hospital and Health Italian Sanitary System recommendations. We performed a combined retrospective and prospective study in which we compared the impact of extra measures against the hospital standard. Results: We analysed data from 941 patients. The infection prevention and control programme was associated with a reduction in the incidence of hospital-acquired infections (17 vs. 8.9%, p <0.01). No further reduction was present after the COVID-19 measures had been imposed. The impact of the infection prevention and control programme remained significant even after controlling for the effects of confounding variables (odds ratio 0.44, 95% CI 0.26-0.73, p = 0.002). Furthermore, the adoption of the programme reduced the prevalence of multidrug-resistant organisms and decreased rates of empiric antibiotic treatment failure and the development of septic states. Conclusions: The infection prevention and control programme decreased the incidence of hospital-acquired infections by nearly 50%. Furthermore, the programme also reduced the prevalence of most of the secondary outcomes. Based on the results of this study, we encourage other liver centres to adopt infection prevention and control programmes. Impact and implications: Infections are a life-threatening problem for patients with liver cirrhosis. Moreover, hospital-acquired infections are even more alarming owing to the high prevalence of multidrug-resistant bacteria. This study analysed a large cohort of hospitalised patients with cirrhosis from three different periods. Unlike in the first period, an infection prevention programme was applied in the second period, reducing the number of hospital-acquired infections and containing multidrug-resistant bacteria. In the third period, we imposed even more stringent measures to minimise the impact of the COVID-19 outbreak. However, these measures did not result in a further reduction in hospital-acquired infections.

Epidemiology and Disease Burden of Alcohol Associated Liver Disease.

Consumption of alcohol in excess leads to substantial medical, economic, and societal burdens. Approximately 5.3% of all global deaths may be attributed to alcohol consumption. Moreover, the burden of alcohol associated liver disease (ALD) accounts for 5.1% of all disease and injury worldwide. Alcohol use disorder (AUD) affects men more than women globally with significant years of life loss to disability in low, middle and well-developed countries. Precise data on global estimates of alcohol related steatosis, alcohol related hepatitis, and alcohol related cirrhosis have been challenging to obtain. In the United States (US), alcohol related steatosis has been estimated at 4.3% based on NHANES data which has remained stable over 14 years. However, alcohol-related fibrotic liver disease has increased over the same period. In those with AUD, the prevalence of alcohol related hepatitis has been estimated at 10-35%. Globally, the prevalence of alcohol-associated cirrhosis has been estimated at 23.6 million individuals for compensated cirrhosis and 2.46 million for those with decompensated cirrhosis. The contribution of ALD to global mortality and disease burden of liver related deaths is substantial. In 2016 liver disease related to AUD contributed to 50% of the estimated liver disease deaths for age groups 15 years and above. Data from the US report high cost burdens associated with those admitted with alcohol-related liver complications. Finally, the recent COVID-19 pandemic has been associated with marked increase in alcohol consumption worldwide and will likely increase the burden of ALD.

"Time Consuming -but Time Well Spent": Hepatologists' Experiences with Delivering Palliative Care to Patients with End-Stage Liver Disease and Their Caregivers

Background: Palliative care (PC) is an integral part of managing patients with chronic illness and high symptom burden including end-stage liver disease (ESLD). Given the deficit in PC workforce, we trained Hepatologists with primary PC skills as a part of a comparative effectiveness trial (NCT03540771). This study explored the experiences of hepatologists trained to provide PC to patients with ESLD and their caregivers. Method(s): We conducted a qualitative interview study within the context of Pal-Liver, a PCORI-funded, 18-institution cluster-randomized comparative effectiveness trial of PC delivered by hepatologists (10 sites) vs PC specialist (8 sites) to ESLD patients and caregivers. Hepatologists completed a 12-week training course to develop skills in delivering primary PC for ESLD patients. Trained interviewers used a semi-structured guide to interview hepatologists (n=15) and PC specialists (n=15) to explore overall experiences in providing ESLD care, pre-and post-study challenges and benefits, and for hepatologists, experiences with training and providing primary palliative care. Phone interviews were digitally-recorded, transcribed verbatim, coded, and analyzed aided by NVIVO 12 software. Using a consensus-driven code book manifest and latent themes emerged. Here we report preliminary analysis of hepatologists' perspectives. Result(s): Hepatologists (n=15) 70% female;77% white, mean age 48 years from 8 hepatologist-provided palliative care institutions reported themes of: 1) primary PC training beneficial;2) time consuming but "time well spent" with additional primary PC integrated within routine ESLD care;3) ESLD care boundaries vs overlap: Who does what & when?;4) Covid-19 impact: challenges and opportunities;5) increased focus on caregivers' needs;6) patient reported outcome (PROs) measures improved communication about prognosis and tailoring PC interventions for physical and emotional symptoms, and 7) need for more case discussions and practical strategies. Conclusion(s): Training on primary PC skills assisted hepatologists to provide additional support to patients and increased their realization of caregivers' needs. Boundaries between primary and specialist PC for patients with ESLD are not well demarcated. Hepatologists found PROs useful in tailoring PC interventions. Future analysis will include comparisons between hepatology and specialist delivered PC to inform a pragmatic approach. (Figure Presented).

Impact of COVID-19 on Increased Mortality in Liver Transplant Recipients in United States

Purpose: COVID-19 pandemic has had a significant impact on access to routine healthcare in both hospitalized and out-patient settings. This impact was also noted in various aspects of pre and post-transplant care of liver transplant (LT) recipients. The aim of our study was to analyze the direct and indirect impact of COVID-19 on mortality in patients with recent LT. Method(s): We retrospectively analyzed 30-day, 6-month and 1-year mortality data from the UNOS database in adult LT recipients from 3 distinct groups;Pre-COVID (March 11- September 10, 2019: LT and immediate follow-up care before pandemic), Para-COVID (September 11- March10, 2020: LT before pandemic and follow-up care during pandemic), and COVID (March 11- September 10, 2020: LT and follow-up care during pandemic). Result(s): 12,598 LTs were performed during the study period. During COVID period, there was increase in LT for alcoholic liver disease, average MELD score was higher, LT for hepatitis C decreased, use of thymoglobulin induction decreased and waiting time was shorter. During the 30-day period, overall mortality between 3 groups remained same. In the COVID group, mortality from graft failure was higher (7.4 vs 17.9%, p=0.07), rate of infection was lower (14% vs 4.2%, p=0.039), and incidence of graft rejection prior to discharge was higher. During the 6-month follow-up, overall mortality, mortality from malignancy and COVID, and graft failure increased significantly in the COVID group. During the 1-year follow-up period, mortality was highest in COVID group over para-COVID group and lowest in the pre-COVID group. In the COVID group, increased mortality was from graft failure and COVID. Overall mortality in the study cohort directly from COVID was 7.8%, which was highest in the COVID group. Multivariable cox regression for one year mortality showed that risk factors for mortality were COVID period [Hazard Ratio (95%CI) 1.22 (1.02-1.46), p=0.027], older age of recipient, diabetes, portal vein thrombosis, ventilation at the time of transplant, hemodialysis at the time of transplant, re-transplant, and prolonged cold ischemic time. Conclusion(s): COVID-19 significantly impacted LT short term outcomes with increased mortality seen from COVID directly as well as indirectly. During COVID, cautious and lower use of immuno-suppression was likely associated with higher rates of rejection and lower rates of infection. Disruptions in routine post-transplant follow-up likely contributed to increased death from graft failure, malignancy, and poor control of chronic medical conditions like diabetes. (Figure Presented).

A New Chapter in an Evolving Pandemic: Successful Pediatric Liver Transplantation with COVID+ Donors

Purpose: We report the first two pediatric liver transplants utilizing allografts from COVID+ donors, infected at time of organ procurement, demonstrating a pivotal step toward donor pool maximization amid a viral pandemic with poorly understood transmissibility in the pediatric patient. Method(s): This is a prospective and retrospective review of two pediatric liver transplants and their donors who tested positive for SARS-CoV-2 at time of procurement. Data was obtained through the electronic medical record system and UNet DonorNet platform. Result(s): The first donor is a 3-year-old male succumbing to head trauma. 1 of 5 nasopharyngeal swab RT-PCR tests demonstrated COVID-19 positivity while 1 of 3 bronchoalveolar lavage RT-PCR tests indicated SARS-CoV-2 infection. Preceding procurement in the second donor, a 16-month-old male with unknown etiology of cardiorespiratory arrest, 2 nasopharyngeal swab RT-PCR tests and 1 bronchoalveolar lavage RT-PCR test failed to detect SARS-CoV-2 infection. Diagnosis was not made until the Medical Examiner's office repeated a nasopharyngeal swab RT-PCR and archive plasma RT-PCR which were both positive for SARS-CoV-2. The two 2-yearold pediatric liver recipients underwent transplantation in November 2021. Continued follow-up demonstrates successful transplant void of viral transmission or hepatic artery thrombosis as liver chemistries have anticipatorily normalized with excellent graft function. One recipient experienced early portal vein thrombosis treated by interventional radiology with discharge on postoperative day 20. Conclusion(s): This report is the first to describe successful pediatric liver transplants from COVID+ donors. This data reinforces case reports in the adult transplant population of successful use of COVID + donor organs and further supports the judicious use of COVID+ donors for extrapulmonary pediatric organ transplant. The concern for donor-derived transmission must now be weighed against the realized benefit of successful, life-saving transplantation for end stage liver disease in the pediatric patient. (Figure Presented).

18 Month Review of Liver Acuity Circles Allocation

Purpose: Acuity circles (AC) allocation was implemented on 2/4/2020 with a goal of removing DSA and region from liver allocation and broadening the distribution of livers, particularly for highly medically urgent candidates. Method(s): OPTN waitlist and transplant data was analyzed 18 months pre- (8/6/2018- 2/3/2020) and post- (2/4/2020-8/3/2021) AC implementation. Result(s): Post-policy, there were 448 more adult (age 18+ at listing) and 83 less pediatric (<18 at listing) waitlist additions, 570 more adult (age 18+ at transplant) and 4 less pediatric (<18 at transplant) deceased donor liver-alone transplants, and 121 less adult and 12 less pediatric removals for death or too sick. Transplant rates significantly increased overall post-policy, notably in the most medically urgent groups (Figure 1). The national median transplant score for adults remained unchanged at 28 and decreased from 35 to 30 for pediatric transplant recipients, likely due to the increased number of adolescents (age 12-17) transplanted at MELD scores under 29. There was a noticeable shift in the distribution of distance between donor hospital and transplant program, particularly for the most medically urgent groups where larger proportions of livers are coming from 250-500 NMs (Figure 2). Despite this change, median cold ischemia time increased only 11 minutes for adult recipients and 33 minutes for pediatric recipients post-policy. One year post transplant patient survival decreased from 94% pre-policy to 93% post-policy (p=0.02). Conclusion(s): Broader allocation increased transplant rates and livers are traveling longer distances for candidates with greater medical urgency with little effect on cold ischemia time and post-transplant survival. Unfortunately, AC implementation was followed shortly by COVID-19 making it difficult to parse out COVID-19 from potential policy effects. Metrics will continue to be monitored as more data become available. (Figure Presented).

Fast tracking and early on table extubation following living donor liver transplantation, can we expand the criteria?

Background: Traditionally, patients were kept intubated for 48 hours in the postoperative period. Living donor liver transplantation poses a different set of challenges. Most of the predictors mentioned in the literature were, low MELD, low BMI, and with stable comorbidities etc. for early extubation following living donor liver transplantation. We assessed the feasibility of fast tracking and early extubation in our patients, who were not fitting in those mentioned predictors in the literature. Methods: We present a case series of 6 patients who were fast tracked and extubated early, following living donor liver transplantation, out of 22 patients over the last 6 months. Results: All these patients were aged more than 45 yrs, with an average age of 55.8 yrs, average MELD score of 20.8, Child status C, some of our patients had cardio pulmonary comorbidities. patient 2, was COPD, post asymptomatic COVID, with CoRad score3 on HRCT, patient 5, was class 3 obese with no OSA, patient 6, had Hypertension, CAD- triple vessel disease, post CABG 7 yrs back, The intraoperative metabolic parameters like base excess and Lactates were showing good correction and all of them had very minimal inotropic support at the time of extubation, with Norepinephrine < 0.05mcg/kg/minutes. There was no post reperfusion hemodynamic instability or PRS in our patients, the average GRWR in our patients was 0.94, the mean anhepatic period, warm ischemia and cold ischemia times were pretty low. None of them had any significant postoperative complications. Conclusions: We propose, we can safely fast track and extubate early, following living donor liver transplantation with high MELD scores, and stable comorbidities. Further, large studies are needed to look for the feasibility of expanding the criteria for early extubation.

IMPACT OF THE COVID-19 PANDEMIC ON THE EPIDEMIOLOGY OF ALCOHOLRELATED HEPATITIS

Background: Alcohol-related hepatitis (AH) is the most severe form of alcohol-related liver disease, with rising incidence. Stay-at-home orders for the COVID-19 pandemic were associated with increased alcohol consumption. Online sales reported a 262% increase from March 2019 to 2020. Aims: The purpose of this study was to track the epidemiology of hospitalizations for AH by sex before and after the COVID-19 pandemic. We hypothesized that AH would be more severe in females and younger individuals during the pandemic. Methods: Using the Discharge Database, we identified all hospitalizations in Alberta with international classification of disease-10 codes for AH between March 2018 and September 2020. We merged this dataset with provincial laboratory data to identify all inpatient lab values. We calculated Model for End-Stage Liver Disease (MELD) and Maddrey scores and validated a laboratory-based algorithm for AH. Severe AH was defined as Maddrey score > 32. Onset of the pandemic was defined as March 2020. Stratified by pandemic onset, descriptive statistics were done with Chi-squared and Kruskal Wallis tests. Inpatient mortality was assessed as a primary outcome. Binomial regression was used to assess changes in frequency of admission for AH with the denominator as all cirrhosis-related admissions over the same time-period. Results: We identified 991 hospitalizations for AH prior to the pandemic (n=381, 38.5% female) and 417 during the pandemic (n=144, 34.5% female). Hospitalizations for AH significantly increased during the pandemic (p = 0.04) (Figure 1). Median Maddrey score for females (30.5) before the pandemic was significantly higher than for males (22.9), p < 0.01. During the pandemic, median Maddrey for females (28.7) was higher than males 21.4, p = 0.07. Median age at admission was significantly lower for both males and females during the pandemic (age 44 and 41, respectively) as compared to prior (age 47 and 45, respectively) p < 0.05. There was no significant difference in MELD between sexes before (13.5 for females, 14.0 for males, p = 0.15) and during the pandemic (13.3 for females, 13.0 for males, p = 0.75). Additionally, there was no significant difference in mortality between sexes before (10.4% in females, 11.5% in males, p = 0.22) and after the pandemic (9.2% in females, 9.9% in males, p = 0.67). Conclusions: Hospitalizations for AH rose during the pandemic and occurred at younger ages. There was no significant difference in disease severity or mortality before and during the pandemic. Overall, females have more severe AH than males. Public health efforts should continue to be made to educate about the harms of alcohol excess and offer community support. Future studies will expand the trend through multiple pandemic waves. (Figure Presented).

Sarcopenia as a predictor of mortality and complications in cirrhosis patients-A prospective cohort study

Background and aims: Sarcopenia is a promising tool for prognostication of cirrhosis.EWGSOP2 guidelines define sarcopenia based on muscle strength, muscle quantity or quality and physical performance. Many previous studies didn’t use a standardized definition of sarcopenia and was based on skeletal muscle measurement by CT or MRI.Ultrasound guided thigh muscle thickness (TMT) measurement is a validated, cost effective and easy method for assessment of muscle quantity.There is paucity of Indian studies analysing prognostic role of sarcopenia in cirrhosis. To study the predictive role of sarcopenia on mortality and complications in cirrhosis patients. Method: This was a prospective cohort study with 120 consecutive patients each in sarcopenia and no sarcopenia groups. Sarcopeniawas diagnosed based on EWGSOP2 guidelines using ultrasound guided measurement of TMT.They were followed up for 6 months.Kaplan- Meier analysis with LogRank test was used to compare survival and Cox proportional hazards modelwas used for multivariate analysis to determine risk factors of mortality. Results: Cirrhosis patients with sarcopenia[N1 = 120, M:F = 80:40, Median age-58yrs (51–64)] and without sarcopenia[N2 = 120, M:F = 93:27, Median age-54yrs (46.25–60)] were enrolled.Six month cumulative survival was 56.7% and 76.7% in sarcopenia and no sarcopenia groups respectively (p = 0.001).Six month cumulative survival in severe and non-severe sarcopenia was 23.9% and 70% respectively (p = 0.001).Age, sex, nutritional status, sarcopenia status, CTP score, MELD score, Bilirubin, Albumin, INR and Sodium were significantly associated with survival.A multivariate analysis showed sarcopenia (HR = 1.283, 95%CI 1.092–2.130, p = 0.031), female sex (HR = 1.851, 95%CI 1.106–3.097, p = 0.019), CTP class C (HR = 1.447, 95%CI 1.252–1.794, p = 0.002) and MELD score>15 (HR = 1.116, 95%CI 1.056– 2.203, p = 0.05) as independent predictors of mortality. Development of complications like ascites, HE, Covid infection and UGI bleed were significantly higher in sarcopenia group, while SBP, AKI, cellulitis, UTI, HCC and ACLF were not statistically significant between two groups.(Figure Presented) Figure 1. Survival curves in both groups (Log rank p = 0.001) Conclusion: Sarcopenia is an independent prognostic marker of mortality in cirrhosis and is associated with increased risk of complications like ascites, HE, Covid infection and UGI bleed. Severe sarcopenia has even poorer outcome. It appears that addition of sarcopenia to existing scoring systems of cirrhosis will improve prognostication of patients

Intravenous branched chain amino acid infusion is associated with early but ill-sustained recovery of overt hepatic encephalopathy in acute-on-chronic liver failure: a pilot protocol

Background and Aim: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. There is limited evidence regarding HE management in patients with ACLF. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24h, day 3 & day 7. Duration of ICU stay and survival at days 7 and 28 was compared. Methods: CANONIC ACLF patients with HE grades>=2 were randomized into two groups - experimental arm (IV-BCAA - 500mL/day for 3 days + Lactulose;n=39) and comparator arm (Lactulose alone;n=37). Six patients developed COVID-19 after randomization & were excluded (4-experimental arm & 2-comparator arm). HE Grade was assessed by West Haven Classification and Hepatic Encephalopathy Scoring Algorithm (HESA). ACLF severity was determined by CLIF-C ACLF and MELD scores. All patients received standard of care. Results: Both groups were similar in baseline characteristics including grade of HE (2.85 ± 0.75 vs 2.82 ± 0.66;P = 0.864) and CLIF-C ACLF score (54.19 ± 5.55 vs 54.79 ± 5.74;P = 0.655). Overall survival was 40% at 28 days (48.5% vs 31.4%;P=0.143). Significant improvement in HESA score by 1 grade at 24h was seen in 14 patients (40%) in BCAA arm and 6 patients (17.14%) in control group (P=0.034) which translated to shorter ICU stay in the BCAA arm. Median change in HESA score at 24h was significantly more in BCAA arm than control arm (P=0.006), however, this was not sustained at day 3 or 7. Ammonia levels did not correlate with HE grade (Spearman correlation coefficient (-0.0843;P=0.295). Conclusion: Intravenous BCAA leads to early but ill-sustained improvement in grade of HE and reduced ICU stay in ACLF.

Comparative analysis of acute on chronic liver failure related to herbs and anti-tubercular drugs

Objectives: Liver injury precipitated by drugs and herbal medicines( DHMs) can have variable presentations and outcomes. In Indian subcontinent, drug induced liver injury due to Anti-tubercular drugs( ATDs) and inadvertent herbs induced liver injury (HILI) are common. Comparative natural history and outcome of acute-onchronic liver failure(ACLF) due to common DHMs is largely unknown. Materials and Methods: Consecutive in-patients with ACLF precipitated by herbs or ATDs(year 2010-2021) were compared for baseline clinical profile, disease severity, histological features and organ failures. Treatment outcomes and predictors of in-hospital mortality were also analyzed. Results: 529 patients presented with ACLF related to HILI(ACLF-H, n = 430) and ATDs(ACLF-D, n = 99) [Mean Age-47.6 - 14 years, mean MELD score and HVPG were 29.1 - 5.4 and 15.5 - 3.4 mmHg respectively]. 61.4% patients had underlying histological cirrhosis. 21.2% patients had additional superadded acute insult [severe alcoholic hepatitis(n = 66), acute hepatitis E or A(n = 24/15)]. Twelve percent ACLF-H patients presented with clinical cholestasis, autoimmune hepatitis(n = 18) and hypersensitivity reactions(n = 4). Most common recognizable agent associated with ACLF-H was Tinospora cordifolia (n = 35,8.1%), inadvertently used in Indian households during the COVID-19 pandemics. Patients with ACLF-H as compared to ACLF-D had higher male preponderance (70.9% vs. 54.5%;p-0.002) and peripheral eosinophilia (6.4% vs. 1%;p-0.03), clinical cholestasis (19.6% vs 10.8%;p-0.05) and acute kidney injury (44.4% vs. 28.3%;p-0.003) at presentation. Use of plasma exchange(18.5%) had no impact on outcomes. None of the patients underwent liver transplantation. In-hospital mortality(19.2%) was higher in ACLF-D compared to HILI ACLF-H (31.3% vs. 17.2%;p-0.002). Presence of AKI [HR:5.5 (95%CI:2.78 to 11.1)], hepatic encephalopathy[HR:4.4(95%CI:1.76 to 11)] and pneumonia[ HR:7.2(95%CI: 3.59 to 14.65)] were independent predictors of mortality. Conclusion: Herbs and anti-tubercular drugs are common precipitants of ACLF in India and have high in-hospital mortality resulting from sepsis and organ(s) failure. In the absence of specific treatment options, prevention and early and careful monitoring of liver functions is of utmost importance.