Complication Of End-stage Liver Disease Research Articles

Systolic and diastolic impairment in cirrhotic cardiomyopathy: insights from a cross-sectional study

BackgroundCirrhotic cardiomyopathy, an intricate and multifaceted complication of end-stage liver disease, manifests as systolic and diastolic dysfunction in patients without previously diagnosed cardiac disease. Our study aims to investigate the prevalence of systolic and diastolic function in patients with cirrhotic cardiomyopathy in our region.MethodsWe conducted a cross-sectional study on 68 patients with established cirrhosis, and no overt cardiac manifestations, who consequently underwent 2D echocardiography to quantify systolic and diastolic dysfunction, as defined by the 2019 Cirrhotic Cardiomyopathy Consortium. The severity of cirrhosis was determined using various validated scoring systems.ResultsA total of 19 out of 68 (28%) had systolic dysfunction, while 6/68 (9%) had evidence of diastolic dysfunction. Overall prevalence of cirrhotic cardiomyopathy was 23/68 (34%), and the presence of hepatitis C was strongly associated with systolic dysfunction with p-value of 0.007. However, it was not significantly associated with diastolic dysfunction, p-value = 0.59. Logistic regression analysis did not show any significant association between cardiac dysfunction and the severity of liver cirrhosis, as assessed by Child–Pugh, MELD, ALBI, PALBI, portal hypertension, and FIB-4 score (R2 = 3.66, F (13, 39) = 1.33, p = 0.234).ConclusionOur study reveals a remarkable prevalence of cirrhotic cardiomyopathy, which despite being a frequently occurring phenomenon often goes unrecognized. Lack of correlation with the severity of liver cirrhosis, based on currently available scoring system, suggests either a still poorly understood pathological mechanism or requires the development of a new validated reliable scoring system through multi-center longitudinal studies.

A Comparative Analysis of Norepinephrine with Midodrine/Octreotide in Patients with Hepatorenal Syndrome-acute Kidney Injury

Background Hepatorenal Syndrome (HRS) is a severe complication of end-stage liver disease characterized by functional renal impairment. This study aimed to assess the efficacy of norepinephrine compared to midodrine/octreotide in managing patients diagnosed with hepatorenal syndrome type 1. Materials and Methods In this double-blind Randomized Clinical Trial, 50 patients with hepatorenal syndrome type 1 were randomly assigned to the norepinephrine and midodrine/octreotide groups. The norepinephrine group received an initial dose of 1 mg/h (up to a maximum of 4 mg/h) along with daily intravenous injections of 20% albumin (20-40 grams per day) throughout the study period. The control group received midodrine (maximum dose of 15 mg three times a day), octreotide (maximum dose of 200 micrograms intravenously three times a day), and 20 to 40 mg of 20% albumin daily. The primary efficacy measure was the percentage of patients achieving a complete response, defined by the restoration of serum creatinine levels to within 0.3 mg/dl of the baseline by the end of treatment. Results There was no significant difference in the rate of complete response between the norepinephrine group (7/25, 28%) and the midodrine/octreotide group (3/25, 12%) (p=0.15). The mortality rate was 10 (40%) in the norepinephrine group and 12 (48%) in the midodrine/octreotide group. Although the mortality rate was higher in the midodrine/octreotide group (12/25, 48%) compared to the norepinephrine group (10/25, 40%), this difference was not statistically significant (p=0.77). Conclusion The study findings suggest that the norepinephrine treatment regimen can be as effective as or more effective than the midodrine/octreotide regimen in treating hepatorenal syndrome in cirrhotic patients. Therefore, these two treatment regimens can be used interchangeably. Clinical Trial Registration Number IRCT20230228057568N1

The impact of MELD exception points for hydrothorax on posttransplant mortality: a propensity score-matched analysis.

Hepatic hydrothorax is a challenging complication of end-stage liver disease, and.patients with this complication can receive model for end-stage liver disease (MELD) exception points if they meet specific criteria as defined by United Network for Organ Sharing (UNOS). This research aimed to analyze the effect of receiving MELD exception points for hepatic hydrothorax on posttransplant mortality, using a national transplant database. Patients >18 years in the UNOS database awaiting liver transplant between 2012 and 2023 were identified based on their petition for MELD exception points. Using a 1: 1 propensity score-matched analysis, 302 patients who received MELD exception points for hepatic hydrothorax were compared with 302 patients who did not receive MELD exception points.Demographic, clinical and laboratory values were compared. The primary outcome was posttransplant mortality. Multivariate logistic regression controlled for potential confounders. No significant difference was observed in mean age (58.20 vs 57.62 years), mean initial MELD score (16.93 vs 16.54), or mean Child-Pugh score (9.77 vs 9.74) in patients with hepatic hydrothorax receiving MELD exception points versus their matched cohort who did not recieve exception points. The proportion of males was slightly higher among patients who received MELD exception points (57.6% males vs 53.6% males). A majority of patients in both groups had Child-Pugh grade C (>56%). Patients receiving MELD exception points for hepatic hydrothorax had a statistically significant 44% decrease in the odds of posttransplant death compared to those who did not (OR 0.56; 95% CI 0.37-0.88; P = 0.01). Among the combined cohort, each year increase in age resulted in a 3.9% increase in mortality (OR 1.04; 95% CI 1.01-1.07; P = 0.005), and every one-unit increase in serum creatinine resulted in a 40% increase in mortality (OR 1.40; 95% CI 1.03-1.92; P = 0.03). Receiving MELD exception points for hepatic hydrothorax is associated with a significant reduction in the odds of posttransplant mortality. These findings underscore the importance of MELD exception points for hepatic hydrothorax among patients with decompensated cirrhosis, potentially improving patient prioritization for liver transplantation and influencing clinical decision-making.

Utilizing a novel MRI technique to identify adverse muscle composition in end-stage liver disease: A pilot study

Introduction and ObjectivesSarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. Materials and MethodsIn a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. ResultsEighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). ConclusionsThe AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.

Transplantace jater pro deficit alfa-1-antitrypsinu

Summary: Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant genetic condition which manifests with lung emphysema at young age and with liver disease. A point mutation in the SERPINA1 gene, which encodes 1-antitrypsin (AAT), causes a defective secondary structure of the protein, which subsequently accumulates in the endoplasmic reticulum of hepatocytes and is not transported into the blood and body fluids. Deficiency of AAT, which inhibits neutrophil elastase in the lung, thus allows proteolytic damage to the connective tissue of the lung, leading to the development of emphysema. Liver disease is caused by the accumulation of the mutant AAT in liver cells, contributing to proteotoxic liver injury that can lead to liver cirrhosis. Liver transplantation (LT) is the only curative method; after LT, the recipient has the phenotype of the donor organ and normal serum AAT concentrations. The indication for LT should be considered in all patients with AATD and end-stage liver disease. The patients should be referred to the transplant centre when severe complications of liver cirrhosis, such as variceal bleeding, ascites, encephalopathy, and hepatorenal syndrome. In patients with hepatocellular carcinoma, LT represents an optimal treatment modality in the case of an early, unresectable tumour. The timing of LT is crucial; LT should be performed before the patient develops life-threatening complications of end-stage liver disease. LT should be considered in patients of Child-Pugh classification B and C and MELD score of 15 points or higher. Survival of patients after LT for AADT is excellent. Key words: 1-antitrypsin – 1-antitrypsin deficiency – liver cirrhosis – end-stage liver disease – hepatocellular carcinoma – live transplantation

Long-Circulating Vasoactive 1,18-Octadecanedioic Acid-Terlipressin Conjugate.

Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease first reported over a century ago, but its management still poses an unmet challenge. A therapeutic agent found to stabilize the condition is a short cyclic peptide, vasopressin analogue, terlipressin (TP). While TP is commonly prescribed for HRS patients in most parts of the world, it was only recently approved for use in the United States. TP exhibits short circulation half-lives and adverse side effects associated with the dose required. Herein, we present a 1,18-octadecanedioic acid (ODDA) conjugate of the cyclic peptide (ODDA-TP), which enables noncovalent binding to serum albumin via native fatty acid binding modes. ODDA-TP is demonstrated to outperform TP alone in studies including in vitro cellular receptor activation, stability in plasma, pharmacokinetics, and performance in vivo in rats. Specifically, ODDA-TP had an elimination half-life 20 times that of TP alone while exhibiting a superior safety profile.

Assessing the Self-Rating Scale Item as a Measure for Lactulose Adherence

Background/Objective:Hepatic encephalopathy (HE) is a defining complication of end-stage liver disease. The standard treatment is lactulose, but adherence is difficult due to complex dosing regimens and side effects. We adapted a single item self-reported adherence measure - the Self Rating Scale Item (SRSI) - for lactulose use and examined its relationship with clinical events, cognition, and quality of life.&#x0D; Methods:We performed a cross-sectional study of patients with cirrhosis and HE seen at Indiana University Hospital 5/31/2023-7/14/2023. Clinical history and demographic information were collected through electronic health records and patient interviews. Patients provided the SRSI, which reflects their self-perceived ability to take lactulose, bowel movement frequency, perception of missing doses, and quality of life (PROMIS-29+2). Cognition was measured using the Animal Naming Test (ANT). The relationship between the SRSI and other measures was assessed.&#x0D; Results:42 patients met eligibility criteria and enrolled. The median age was 59, and 55% were female. Patients were divided across SRSI categories: ≤good, very good, and excellent. Patients with better adherence were more likely to have ascites, but other demographics were similar between groups. Ascites was present in 43%, 64%, and 93% of ≤good, very good, and excellent categories, respectively. A higher SRSI score was associated with fewer missed doses and more days achieving bowel movement targets. 79% in the ≤good category skipped lactulose doses compared to 29% and 21% in very good and excellent groups. SRSI was not associated with HE-related hospitalizations or ANT. Higher SRSI was associated with improved sleep and cognitive function, with a trend towards decreased fatigue and pain.&#x0D; Conclusion/Potential Impact:The SRSI is associated with other measures of lactulose adherence and quality of life and may be a promising tool to measure lactulose adherence. Adopting the SRSI may be a useful way to improve lactulose dosing, adherence, and health outcomes.

Newly developed sarcopenia after liver transplantation, determined by a fully automated 3D muscle volume estimation on abdominal CT, can predict post-transplant diabetes mellitus and poor survival outcomes

BackgroundLoss of muscle mass is the most common complication of end-stage liver disease and negatively affects outcomes for liver transplantation (LT) recipients. We aimed to determine the prognostic value of a fully automated three-dimensional (3D) muscle volume estimation using deep learning algorithms on abdominal CT in patients who underwent liver transplantation (LT).MethodsThis retrospective study included 107 patients who underwent LT from 2014 to 2015. Serial CT scans, including pre-LT and 1- and 2-year follow-ups were performed. From the CT scans, deep learning-based automated body composition segmentation software was used to calculate muscle volumes in 3D. Sarcopenia was calculated by dividing average skeletal muscle area by height squared. Newly developed-(ND) sarcopenia was defined as the onset of sarcopenia 1 or 2 years after LT in patients without a history of sarcopenia before LT. Patients’ clinical characteristics, including post-transplant diabetes mellitus (PTDM) and Model for end-stage liver disease score, were compared according to the presence or absence of sarcopenia after LT. A subgroup analysis was performed in the post-LT sarcopenic group. The Kaplan–Meier method was used for overall survival (OS).ResultsPatients with ND-sarcopenia had poorer OS than those who did not (P = 0.04, hazard ratio [HR], 3.34; 95% confidence interval [CI] 1.05 – 10.7). In the subgroup analysis for post-LT sarcopenia (n = 94), 34 patients (36.2%) had ND-sarcopenia. Patients with ND-sarcopenia had significantly worse OS (P = 0.002, HR 7.12; 95% CI 2.00 – 25.32) and higher PTDM occurrence rates (P = 0.02, HR 4.93; 95% CI 1.18 – 20.54) than those with sarcopenia prior to LT.ConclusionND-sarcopenia determined by muscle volume on abdominal CT can predict poor survival outcomes and the occurrence of PTDM for LT recipients.

Palliative care and end of life care in decompensated cirrhosis.

Palliative care and end of life care in decompensated cirrhosis.

Treatment and outcome of hepatorenal syndrome in Japan: a retrospective cohort study using a national inpatient database

BackgroundHepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database.MethodsPatients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups’ baseline patient characteristics and treatments were compared.ResultsThe mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child–Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis.ConclusionsHRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice.

Management of Chronic Hepatitis B in HIV-Coinfected Patients.

Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) has a more rapid progression than in HBV-monoinfected patients, leading to end-stage liver disease complications, including hepatocellular carcinoma. Therefore, the adequate management of CHB is considered a priority in HIV-coinfected patients. Several guidelines have highlighted this issue and have provided recommendations for preventing and treating HBV infection. This article discusses the management of liver disease in patients with HIV/HBV coinfection and summarizes the current and future therapeutic options for treating chronic hepatitis B in this setting.

Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada

Background & AimsHDV affects 4.5–13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network.MethodsAnti-HDV IgG-positive specimens collected between 2012 and 2019 were RNA tested and the genotype determined. Patients enrolled in the Canadian HBV Network were >18 years of age and HBsAg-positive. Clinical data collected included risk factors, demographics, comorbidities, treatment, fibrosis assessment, and hepatic complications.ResultsOf the referred patients, 338/7,080 (4.8%, 95% CI 4.3–5.3) were HDV seropositive, with 219/338 RNA-positive (64.8%, 95% CI 59.6–69.7). The HDV+ cohort were more likely to be born in Canada, to be White or Black/African/Caribbean than Asian, and reporting high-risk behaviours, compared with HBV mono-infected patients. Cirrhosis, complications of end-stage liver disease, and liver transplantation were significantly more frequent in the HDV+ cohort. HDV viraemia was significantly associated with elevated liver transaminases and cirrhosis. Five HDV genotypes were observed among referred patients but no association between genotype and clinical outcome was detected within the HDV+ cohort.ConclusionsNearly 5% of the Canadian HBV referral population is HDV seropositive. HDV infection is highly associated with risk behaviours and both domestic and foreign-born patients with CHB. HDV was significantly associated with progressive liver disease highlighting the need for increased screening and surveillance of HDV in Canada.Lay summaryEvidence of HDV infection was observed in approximately 5% of Canadians who were infected with HBV referred to medical specialists. HDV-positive patients were more likely to be male, born in Canada, or White or Black/African/Caribbean compared to Asian, and to have reported high-risk activities such as injection or intranasal drug use or high-risk sexual contact compared with patients infected with only HBV. Patients infected with HDV were also more likely to suffer severe liver disease, including liver cancer, compared with HBV mono-infected patients.

Burden of Hepatitis B Virus at a Tertiary Care Hospital, Doda, Jammu and Kashmir, India: A Cross-sectional Study

Introduction: Hepatitis B Virus (HBV) causes most frequent chronic liver disease of infectious origin in human beings worldwide, with more than 600,000 deaths caused by end-stage liver disease complications per year. The most used test for identifying acute HBV infections and carriers is the detection of HBsAg. Immunochromatography assays have been suggested for routine use in clinical microbiology laboratories for the detection of HBsAg since they are easy to use, affordable, don’t need specialised equipment, and are straightforward to run. Compared to commercially available HEPA card kit for the detection of the same markers, Enzyme Linked Immunosorbent Assay (ELISA) was shown to be more sensitive for the detection of HBsAg. This study is first of its kind in District Doda, Jammu and Kashmir, India. Aim: To know the burden of HBV in a tertiary Care Hospital, Government Medical College, Doda using HEPA card kit and ELISA method. Materials and Methods: The present hospital-based crosssectional study was carried out in the Department of Microbiology, Government Medical College and Hospital, Doda Jammu and Kashmir, India during the period from January 2020 to December 2020. The study comprised blood samples from all age groups referred by clinical departments for testing HBsAg. Tests were performed using an immunochromatographic technique (Hepa Card Diagnostic enterprises) for the qualitative detection of HBsAg, and results were interpreted in accordance with the manufacturer’s guidelines. The collected data was analysed in microsoft excel sheet using Chi-square test to know the burden of HBV infection. Results: Among total number of 5,448 samples tested, 50 (0.92%) were positive for HBsAg which comes under low epidemicity (&lt;2%) as per World Health Organisation (WHO) guidelines. The number of positive females and males were 30 (0.84%) and 20 (1.07%), respectively. Females were predominate over males and majority of the positive patients (N=29) were younger than 40 years though prevalance (2.1%) was higher in age group above 40 years. All samples which shows positive by rapid test were also shown positive by ELISA test. Conclusion: Overall prevalence of HBV was 0.92% which comes under low epidemicity (&lt;2%) as per WHO guidelines. It can be an alternate option for community based studies and also helps to improve the public health and to prevent the spreading of disease in the local population.

Complications of End-Stage Liver Disease: Advances from a Clinical Viewpoint

Complications of End-Stage Liver Disease: Advances from a Clinical Viewpoint

Cerebrolysin Prevents Brain Injury in a Mouse Model of Liver Damage.

Liver damage can lead to secondary organ damage by toxic substances and catabolic products accumulation which can increase the permeability of blood-brain barrier, leading to cognitive impairment. The only real treatment for end stage liver failure is grafting. With some, but not all, neurological symptoms subsiding after transplantation, the presence of brain damage can impair both the short and long-term outcome. We tested if Cerebrolysin can prevent brain injury in an experimental model of non-viral liver damage in mice. Behavior, abdominal ultrasound evaluation and immunohistochemistry were used to evaluate the animals. No ultrasound or behavior differences were found between the control and treated animals, with both groups displaying more anxiety and no short-term memory benefit compared to sham mice. Cerebrolysin treatment was able to maintain a normal level of cortical NeuN+ cells and induced an increase in the area occupied by BrdU+ cells. Surprisingly, no difference was observed when investigating Iba1+ cells. With neurological complications of end-stage liver disease impacting the rehabilitation of patients receiving liver grafts, a neuroprotective treatment of patients on the waiting lists might improve their rehabilitation outcome by ensuring a minimal cerebral damage.

Symptom Classes in Decompensated Liver Disease

Patients with decompensated liver disease have been categorized by disease severity. This analysis sought to classify patients with end-stage liver disease based on symptoms rather than disease state and to identify distinct severity classes of physical and psychological symptoms. Patients with a model for end-stage liver disease-sodium score of 15 or higher were recruited from liver clinics in 2 health care organizations. They completed the Condensed Memorial Symptom Assessment Scale, Revised Ways of Coping Checklist, Patient Health Questionnaire, Life Orientation Test-Revised, and the Short-Form Health Survey. Cross-sectional data were analyzed using latent class mixture modeling. The sample (N= 191; age, 56.6 ± 11.1 y; 33.5% ETOH; 28.3% nonalcoholic fatty liver disease; 13.1% autoimmune/primary biliary cholangitis/primary sclerosing cholangitis) was predominantly male (64.2%), Child-Turcotte-Pugh class C (49.5%), with an average model for end-stage liver disease-sodium score of 18.7 ± 4.9. Three distinct classes of symptoms were identified, as follows: mild (26.7%), moderate (41.4%), or severe (31.9%) symptoms. Symptom classes were independent of disease severity and demographic characteristics, except age. All Condensed Memorial Symptom Assessment Scale symptoms and Patient Health Questionnaire scores were significantly different across the 3 classes (P &lt; .05). The symptom classes also differed significantly in physical and mental quality of life, optimism, and avoidance coping behaviors (all P &lt; .001). Patient-reported symptom severity occurred independent of disease severity, contrary to common assumptions. Focusing on the moderate and severe symptom classes as well as patient history of end-stage liver disease complications may enhance providers' ability to improve symptom management for this population.

The Gut-Liver Axis in Chronic Liver Disease: A Macrophage Perspective.

Chronic liver disease (CLD) is a growing health concern which accounts for two million deaths per year. Obesity, alcohol overconsumption, and progressive cholestasis are commonly characterized by persistent low-grade inflammation and advancing fibrosis, which form the basis for development of end-stage liver disease complications, including hepatocellular carcinoma. CLD pathophysiology extends to the intestinal tract and is characterized by intestinal dysbiosis, bile acid dysregulation, and gut barrier disruption. In addition, macrophages are key players in CLD progression and intestinal barrier breakdown. Emerging studies are unveiling macrophage heterogeneity and driving factors of their plasticity in health and disease. To date, in-depth investigation of how gut–liver axis disruption impacts the hepatic and intestinal macrophage pool in CLD pathogenesis is scarce. In this review, we give an overview of the role of intestinal and hepatic macrophages in homeostasis and gut–liver axis disruption in progressive stages of CLD.

A Review for the Practicing Clinician: Hepatorenal Syndrome, a Form of Acute Kidney Injury, in Patients with Cirrhosis.

The hepatorenal syndrome type of acute kidney injury (HRS-AKI), formerly known as type 1 hepatorenal syndrome, is a rapidly progressing renal failure that occurs in many patients with advanced cirrhosis and ascites. Accumulating evidence has led to a recent evolution of diagnostic criteria for this serious complication of end-stage liver disease. The aim of this review is to provide an overview of disease-related characteristics and therapeutic management of patients with HRS-AKI. Relevant literature was compiled to support discussion of the pathophysiology, diagnosis, prognosis, associated conditions, prevention, treatment, and management of HRS-AKI. Onset of HRS-AKI is characterized by sudden severe renal vasoconstriction, leading to an acute reduction in glomerular filtration rate and rapid, potentially life-threatening, renal deterioration. Although our understanding of disease pathophysiology continues to evolve, etiology of HRS-AKI likely involves systemic hemodynamic changes caused by liver disease, inflammation, and damage to renal parenchyma. There is currently no gold standard for diagnosis, which typically involves a clinical workup, abdominal imaging, and laboratory assessments. The current consensus definition of HRS-AKI includes proposed diagnostic criteria based on changes in serum creatinine levels tailored for high sensitivity, and rapid detection to accelerate diagnosis and treatment initiation. The only potential cure for HRS-AKI is liver transplantation; however, vasoconstrictive agents and other supportive measures are used as needed to help maintain survival for patients who are awaiting or are ineligible for transplantation. The severity of HRS-AKI, complex pathology, limited treatment options, and range of associated conditions pose significant challenges for both patients and care providers.

The Current Management of Hepatorenal Syndrome-Acute Kidney Injury in the United States and the Potential of Terlipressin.

Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]–AKI) is a severe and often fatal complication of end‐stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off‐label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short‐term prognosis in patients with HRS‐AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS‐AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS‐AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS‐AKI and supported by recommendations for first‐line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS‐AKI and the potential benefits if terlipressin was approved in the United States.

Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome.

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.