Older Patients With Acute on Chronic Liver Failure Have a Higher Waitlist Mortality, but Acceptable Post Liver Transplantation Survival When Compared To Younger Patients.

BACKGROUND & AIMS: There is a paucity of studies on older patients (≥65 years) who develop acute on chronic liver failure (ACLF). The objectives of our study were to determine clinical characteristics and outcomes of older patients listed for liver transplantation (LT). METHODS: Adults listed for LT with estimated ACLF (Est-ACLF) between 2005 and 2021 were identified using the United Network for Organ Sharing database and subdivided into older and younger age (18-64 years) groups. Kaplan-Meier survival analyses were used to evaluate survival, and a competing-risk model (Fine-Gray) was used to evaluate risk factors for survival on the waitlist. Logistic regression was done to evaluate risk factors. RESULTS: A total of 4313 older (14%) and 26,628 younger (86%) patients were listed for LT, and 2142 (49.6%) and 16,931 (63.5%) were transplanted, respectively. Older patients had a higher 30-day waitlist mortality than younger patients (20.4% vs 16.7%; P < .0001); this was more pronounced in Est-ACLF-2 (23.7% vs 14.8%; P < .0001) and Est-ACLF-3 (43.3% vs 29.9%; P < .0001). One-year post-LT, patient survival in older patients with Est-ACLF grades 1, 2, and 3 were 86.4%, 85.5%, and 77% respectively; younger patients had better survival across all Est-ACLF grades. When adjusted for transplant eras, respiratory failure was the only independent risk factor for increased 1-year post-LT mortality in older patients. CONCLUSION: Older patients with Est-CLF had significantly higher waitlist mortality than younger patients, but had acceptable 1-year post-LT survival including those with Est-ACLF-3; therefore, age alone should not be considered as a contraindication for LT. Older patients with respiratory failure should be carefully selected for LT.

State of the Art: Test all for Anti-Hepatitis D Virus and Reflex to Hepatitis D Virus RNA Polymerase Chain Reaction Quantification.

Diagnosis of HDV exposure is based on clinical assays of anti-hepatitis D antibody and current infection with hepatitis D RNA PCR. The role of hepatitis D antigen testing is not yet defined. RT-qPCR is the gold standard for measuring HDV RNA viral load, which is used to assess response to the treatment of HDV infection. Gaps in testing include poor sensitivity of antigen testing and quantitative HDV RNA accuracy can be affected by the genotypic variability of the virus and variation in laboratory techniques. There is also a limitation in HDV testing due to access, cost, and limited knowledge of testing indications. Droplet digital PCR promises to be a more accurate method to quantify HDV RNA. Also, the recent development of a rapid HDV detection test could prove useful in resource-limited areas.

Liver Transplantation Within 7-Days of Listing Improves Survival in ACLF-3.

BACKGROUND AND AIMS: Patients with acute on chronic liver failure (ACLF-3) have a very high short-term mortality without liver transplantation (LT). Our objective was to determine whether early LT (ELT; ≤ 7 days from listing) had an impact on 1 year patient (PS) in patients with ACLF-3 compared to late LT (LLT; days 8-28 from listing). METHODS: All adults with ACLF-3 listed for LT with the United Network for Organ Sharing (UNOS) between 2005 and 2021 were included. We excluded status one patients and those with liver cancer or listed for multi-organ or living donor transplants. ACLF patients were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Patients were categorized as ACLF-3a and ACLF-3b. RESULTS: During the study period, 7607 patients were listed with ACLF-3 (3a-4520, 3b-3087); 3498 patients with ACLF-3 underwent ELT and 1308 had LLT. The overall 1 year PS after listing was 64.4% in ACLF-3a and 50% in ACLF-3b. In 4806 ACLF-3 patients who underwent LT, 1 year PS was 86.2%, but those who had ELT had higher survival (87.1 vs. 83.6%, P = 0.001) than the LLT group. These survival benefits were seen in both ACLF-3a and ACLF-3b. On multivariable analysis, age (HR 1.02, CI 1.01-1.03), diabetes (HR 1.40, CI 1.16-1.68), respiratory failure (HR 1.76, CI 1.50-2.08), donor risk index > 1.7 (HR 1.24, CI 1.06-1.45), and LLT (HR 1.20, CI 1.02-1.43) were independent predictors of higher 1 year mortality while higher albumin (HR 0.89, CI 0.80-0.98) was associated with reduced mortality. CONCLUSION: Early LT (≤ 7 days from listing) in ACLF-3 is associated with better 1 year survival compared to late LT (days 8-28 from listing).

Liver transplantation in patients with acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome associated with a very high short-term mortality. Hence, the ongoing assessment of treatment response, an expedited liver transplant evaluation and listing, and the determination of futility of treatment are critical for optimal outcomes. In this review, we appraise our current understanding of the timing and futility of liver transplantation, and the short- and long-term outcomes including the quality of life after deceased or live donor liver transplantation in those with ACLF.

Impact of Hyponatremia on Morbidity, Mortality, and Resource Utilization in Portal Hypertensive Ascites: A Nationwide Analysis.

Background and aims: Ascites and hyponatremia are important milestones of worsening portal hypertension in those with cirrhosis. The objective of our study was to evaluate the differences in clinical characteristics, resource utilization, and disposition of hospitalized cirrhotic patients with ascites with and without hyponatremia. Methods: The National Inpatient Sample (NIS) database was used to identify all adult hospitalized patients with a diagnosis of cirrhosis and ascites with or without hyponatremia from 2016 to 2017 using ICD-10 codes. Results: During the study period, 10,187 (7.6%) hospitalized patients with cirrhosis had ascites and hyponatremia and 34,555 (24.3%) had ascites but no hyponatremia. Elixhauser comorbidity score, excluding liver disease, was higher in hyponatremic patients (median 21 vs. 12, P < 0.001). Acute kidney injury (50.3% vs. 32.8%, P < 0.001) and sepsis (16.8% vs. 11.8%, P < 0.001) were more common in hyponatremic patients compared to those without hyponatremia. Similarly, acute respiratory failure, coagulopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, acute (on chronic) liver failure, and liver cancer were more common in hyponatremic patients. Hyponatremia patients had a higher number of inpatient procedures, longer (6 days vs. 4 days, P < 0.001) hospital stay, and had higher hospital charges ($97,327 vs. $72,278, P < 0.01) than those without hyponatremia. Inpatient mortality was 38% higher in hyponatremic patients (9.8% vs. 7.1%, P < 0.001) compared to those without hyponatremia. Additionally, hyponatremic patients were less likely to have routine home discharges with self-care. Conclusion: In conclusion, using a large and diverse national cohort of unselected patients, we were able to show that hyponatremia in patients with cirrhosis and ascites is associated with poor clinical outcomes and increased resource utilization.

A model to predict inhospital mortality in patients with cirrhosis, ascites and hyponatremia.

BACKGROUND AND OBJECTIVE: Hypervolemic hyponatremia is a late complication of portal hypertension. Hyponatremia is associated with a higher mortality in hospitalized patients. In this study, we evaluated the risk factors for inhospital mortality and developed a mortality prediction model in patients with cirrhosis and hyponatremia. METHODS: Using the national inpatient sample data for years 2016 and 2017, we identified cirrhotic patients hospitalized with ascites and hyponatremia (n = 9153). We identified independent risk factors of inhospital mortality and developed a prediction model in a training group and assessed its accuracy in a validation group. To enhance the clinical utility, we further stratified patients into low-, intermediate-, and high-risk mortality risk groups using cutoff points selected by decision tree analysis. RESULTS: The inhospital mortality in our cohort was 10.2% (n = 846). Multivariable analysis showed that age at least 65 years, variceal bleeding, sepsis, coagulopathy, and acute-on-chronic liver failure (ACLF defined as two or more organ failures) were independent risk factors for mortality. The prediction model using these five risk factors had an AUROC of 0.80 [95% confidence interval (CI), 0.78-0.82] for the training data and 0.83 (95% CI, 0.80-0.86) for the validation data. The mortality risks in the low-, intermediate-, and high-risk groups were 4% (95% CI, 3-4), 29% (95% CI, 28-33), and 43% (95% CI, 37-50), respectively. CONCLUSION: We have developed a clinically meaningful inhospital prognostic model with excellent discrimination that will enable clinicians to risk stratify hospitalized patients with hyponatremia, ascites, and cirrhosis.

Vaccination in Chronic Liver Disease: An Update.

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

Mortality and health care burden of Budd Chiari syndrome in the United States: A nationwide analysis (1998-2017).

BACKGROUND: The Budd Chiari syndrome (BCS) is a rare and potentially fatal disease, but there is a paucity of data on the in- hospital mortality as well its economic burden on the health care system. AIM: To evaluate trends in mortality, length of hospital stays and resource utilization among inpatients with BCS. METHODS: Data on all adult patients with a diagnosis of BCS were extracted from the National Inpatient Sample (NIS) from 1998 to 2017. To make inferences regarding the national estimates for the total number of BCS discharges across the study period, sample weights were applied to each admission per recommendations from the NIS. RESULTS: During the study period, there were 3591 (8.73%) in-patient deaths. The overall in-hospital mortality rates among BCS patients decreased from 18% in 1998 to 8% in 2017; the mortality decreased by 4.41% (P < 0.0001) every year. On multivariate analysis, older age, higher comorbidity score, acute liver failure, acute kidney injury, acute respiratory failure, hepatic encephalopathy, hepatorenal syndrome, inferior vena cava thrombosis, intestinal infarct, sepsis/septic shock and cancer were associated increased risk of mortality. The average of length of stay was 8.8 d and it consistently decreased by 2.04% (95%CI: -2.67%, -1.41%, P < 0.001) from 12.7 d in 1998 to 7.6 d in 2017.The average total charges after adjusted for Medical Care Consumers Price Index to 2017 dollars during the time period was $94440 and the annual percentage change increased by 1.15% (95%CI: 0.35%, 1.96%, P = 0.005) from $95515 in 1998 to $103850 in 2017. CONCLUSION: The in-hospital mortality rate for patients admitted with BCS in the United States has reduced between 1998 and 2017 and this may a reflection of better management of these patients.

A Scoring Model to Predict In-Hospital Mortality in Patients With Budd-Chiari Syndrome.

INTRODUCTION: A model that can predict short-term mortality in patients with the Budd-Chiari syndrome (BCS) with a high degree of accuracy is currently lacking. The primary objective of our study was to develop an easy-to-use in-hospital mortality prediction model in patients with BCS using easily available clinical variables. METHODS: Data were extracted from the National Inpatient Sample to identify all adult patients with a listed diagnosis of BCS from 2008 to 2017 using ICD-9 or ICD-10 codes. After identifying independent risk factors of in-hospital mortality, we developed a prediction model using logistic regression analysis. The model was built and validated in a training and a validation data set, respectively. Using the model, we risk stratified patients into low-, intermediate-, and high-risk groups. RESULTS: Between 2008 and 2017, we identified a total of 5,306 (weighted sample size 26,110) discharge diagnosis of patients with BCS, with an overall in-hospital mortality of 7.14%. The independent risk factors that predicted mortality were age of 50 years or older, ascites, sepsis, acute respiratory failure, acute liver failure, hepatorenal syndrome, and cancers. The mortality prediction model that incorporated these risk factors had an area under the receiver operating characteristic curve of 0.87 (95% CI 0.85-0.95) for the training data and 0.89 (95% CI 0.86-0.92) for the validation data. Patients with low-, intermediate-, and high-risk scores had a predicted in-patient mortality of 4%, 30%, and 66%, respectively. DISCUSSION: Using a national administrative database, we developed a reliable in-patient mortality prediction model with an excellent accuracy. The model was able to risk stratify patients into low-, intermediate-, and high-risk groups.

A Nationwide Analysis of Budd-Chiari Syndrome in the United States.

OBJECTIVE: The Budd-Chiari Syndrome (BCS) is a rare disorder characterized by hepatic venous outflow obstruction. The primary objectives of our study were to assess temporal trends in the prevalence of BCS among hospitalized patients in the United States using the National Inpatient Sample (NIS) database and to evaluate demographics, risk factors, and common presentation of BCS. METHODS: Data were extracted from the NIS to identify patients >18 years of age using all listed diagnosis of BCS from 1998 to 2017 and analyzed. RESULTS: Between 1998 and 2017, we identified a total of 8435 hospitalizations related to BCS. Over the 19-year period, the hospitalization rate for BCS increased consistently from 4.96 per 1,000,000 US population in 1998 to 10.44 per 1,000,000 in 2017, with an annual percentage change increase of 4.41% (95% confidence interval [CI]: 4.23%-4.59%, P < 0.0001). The most common risk factor (7.75%) was myeloproliferative disorder (essential thrombocythemia, polycythemia vera, myelofibrosis, chronic myeloid leukemia) followed (7.32%) by a hypercoagulable state (primary thrombophilia, protein C deficiency, factor V Leiden mutation, antiphospholipid antibody syndrome or prothrombin gene mutation) and paroxysmal nocturnal hemoglobinuria (1.63%). Cirrhosis was present in 18.7%, Portal vein thrombosis in 7.9%, and inferior vena cava thrombosis in 6.4%. The most common manifestations of BCS were ascites (29.9%) or acute kidney injury (18.8%) followed by hepatic encephalopathy (9.6%) and acute liver failure (5.6%). CONCLUSION: This large population-based study from the United States showed increasing hospitalizations related to BCS. Common presentation was ascites and acute kidney injury.

Acute liver failure in Budd-Chiari syndrome and a model to predict mortality.

BACKGROUND AND OBJECTIVE: Acute liver failure (ALF) occurs in approximately 1-2% of patients with Budd-Chiari syndrome (BCS). The primary objective of our study was to study the outcome of patients with BCS-ALF using the National Inpatient Sample (NIS) database and develop a mortality prediction model. DESIGN: We identified all adult patients with BCS, with and without ALF, using ICD-9 or ICD-10. Using clinical variables, we identified risk factors for in-hospital mortality and developed a prediction model using logistic regression analysis. The model was built and validated in a training and validation datasets. RESULTS: Between 2008 and 2017, of the estimated total of 5,306 (weighted sample size 26,110) BCS discharges, 325 (6.1%) patients (weighted sample size 1,598) presented with ALF. Of 325 BCS-ALF patients, 114 (34.7%, weighted n = 554) died and in contrast only 267 of 4,981 (5%, weighted n = 1310) without ALF died during the hospitalization. The independent risk factors that predicted mortality were age 50 years or older, acute respiratory failure, spontaneous bacterial peritonitis, sepsis and cancers. The prediction model that incorporated these risk factors had an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI 0.80-0.90) for training data and 0.80 (95% CI 0.71-0.89) for validation data. The predicted mortality risk with low (score < 6), intermediate (score 6-16), and high risk (score ≥ 17) scores were 8%, 37% and 71%, respectively. CONCLUSION: ALF due to BCS is associated with a very high in-hospital mortality that could be predicted with reasonable accuracy.

Outcomes of status 1 liver transplantation for Budd-Chiari Syndrome with fulminant hepatic failure.

There is a paucity of data on the outcome of liver transplantation (LT) in Budd-Chiari Syndrome (BCS) patients who are listed as status 1. The objective of our study was to determine patient or graft survival following LT in status 1 BCS patients. We utilized United Network for Organ Sharing (UNOS) database to identify all adult patients (> 18 years of age) listed as status 1 with a primary diagnosis of BCS in the United States from 1998 to 2018, and analyzed their outcomes and compared it to non-status 1 BCS patients. Four hundred and forty-six patients with BCS underwent LT between 1998 and 2018, and of these 55 (12.3%) were listed as status 1. There was no difference in long-term post-liver transplant or "intention-to-treat" survival from the time of listing to death or the last day of follow-up between status 1 and non-status 1 groups. Graft and patient survival at 5 years for status 1 patients were 75% and 82%, respectively. Cox regression analysis showed that patients listed as status 1 (aHR: 0.45, p < .02) were associated with a better survival. BCS patients listed as status 1 have excellent survival following emergency LT.

What GI Physicians Need to Know During COVID-19 Pandemic.

The worldwide pandemic of COVID-19, caused by the virus SARS-CoV-2, continues to cause significant morbidity and mortality in both low- and high-income countries. Although COVID-19 is predominantly a respiratory illness, other systems including gastrointestinal (GI) system and liver may be involved because of the ubiquitous nature of ACE-2 receptors in various cell lines that SARS-CoV-2 utilizes to enter host cells. It appears that GI symptoms and liver enzyme abnormalities are common in COVID-19. The involvement of the GI tract and liver correlates with the severity of disease. A minority (10-20%) of patients with COVID-19 may also present initially with only GI complaints. The most common GI symptoms are anorexia, loss of smell, nausea, vomiting, and diarrhea. Viral RNA can be detected in stool in up to 50% of patients, sometimes even after pharyngeal clearance, but it is unclear whether fecal-oral transmission occurs. Liver enzymes are elevated, usually mild (2-3 times), in a substantial proportion of patients. There are many confounding factors that could cause liver enzyme abnormalities including medications, sepsis, and hypoxia. Although infection rates in those with preexisting liver disease are similar to that of general population, once infected, patients with liver disease are more likely to have a more severe disease and a higher mortality. There is a paucity of objective data on the optimal preventive or management strategies, but few recommendations for GI physicians based on circumstantial evidence are discussed.

Hyponatremia in Cirrhosis: An Update.

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.

Reversal of NASH fibrosis with pharmacotherapy.

NAFLD is a spectrum of liver disease starting with fatty liver at one end of the spectrum and cirrhosis or liver cancer at the other end. Worldwide, NAFLD has become one of the most common liver diseases and it has also become one of the leading indications for liver transplantation. Our understanding of the NAFLD epidemiology, pathogenesis and its progression to cirrhosis has improved over the last 2 decades. Currently, however, there are no FDA-approved treatment options for fibrosis resulting from NAFLD. A number of compounds targeting multiple pathways involved in the progression of NAFLD are currently in phase 2-3 trials. In this review, we will briefly discuss the epidemiology, the pathogenesis and the current status of treatment of NAFLD.

Gastrointestinal Failure in Critically Ill Patients With Cirrhosis.

Gastrointestinal failure (GIF) is frequent in patients managed in the intensive care units and manifests as gut paralysis or ileus. GIF is often associated with sepsis or multiorgan failure. In critically ill patients, the precipitating causes of GIF include inflammation, sepsis, electrolyte abnormalities, and acidosis. It is possible that GIF is associated with an increase in bacterial translocation, especially in those with cirrhosis and portal hypertension, and this may play a significant pathogenic or prognostic role in acute-on-chronic liver failure (ACLF). The critical care literature suggests that GIF is associated with a higher mortality risk. In this review, we summarize the evidence for a potential association between GIF and ACLF and propose treatment options for the management of GIF. Moreover, we suggest GIF to be considered as another organ failure when the severity of ACLF is assessed.