Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial.

INTRODUCTION: Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites. METHODS AND ANALYSIS: ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis. ETHICS AND DISSEMINATION: The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion. TRIAL REGISTRATION NUMBER: NCT05056220 EU CT: 2022-501006-34-01.

Reappraisal of a Renovated Cell-free and Concentrated Ascites Reinfusion Therapy for Malignant Ascites.

BACKGROUND/AIM: Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported. PATIENTS AND METHODS: We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status. RESULTS: Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice. CONCLUSION: Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.

Enhancing proficiency in ascites puncture through procedural simulation: an audit type study investigating medium-term skill retention.

INTRODUCTION: Medical simulation has become an essential teaching method for all health professionals. It not only allows to acquire technical and non-technical knowledge, but also helps the maintenance of acquired knowledge in the medium and long term. Ascites puncture is part of the basic technical procedures learned by medical students during their internship. OBJECTIVES: To evaluate the role of simulation-based learning of ascites puncture on the improvement of theoretical knowledge and maintenance of skills at 3 months. METHODS: We conducted an audit type study with two cycles of data collection at the simulation center at the Faculty of Medicine of Sousse between November 2020 and June 2021. We included learners in their third year of medical studies who had a hospital internship in the gastroenterology department at Sahloul Hospital in Sousse. All learners attended the initial simulation session on ascites fluid puncture. Thereafter, they were free to accept or refuse participation in the evaluation session that was scheduled after 3 months, depending on their availability. RESULTS: Forty learners participated in the procedural simulation of the ascites fluid puncture technique. Thirty-four (85%) were female and six (5%) were male. In our study, we showed that following procedural simulation training of ascites puncture, there was a significant improvement in the theoretical knowledge of the learners (p < 0.000). Objective assessment of technical skills after 3 months showed the benefit of performance maintenance (p < 0.000). CONCLUSION: Our study confirmed the benefit of simulation-based learning on the improvement of theoretical knowledge and the maintenance of technical performance in the medium term.

TPN ascites: an uncommon cause for acute deterioration on mechanical ventilation in a neonate with congenital diaphragmatic hernia.

On ventilation since birth, a term neonate with an antenatally detected left-sided congenital diaphragmatic hernia (CDH) had a sudden worsening in respiratory parameters on day 5 of life. Tube displacement, obstruction, pneumothorax and equipment failure were all ruled out. The examination revealed decreased air entry on the left side and mild abdominal fullness. The chest and abdomen radiographs revealed the absence of bowel gas with a complete whiteout of the abdominal cavity. Since birth, the neonate had received parenteral nutrition via the umbilical venous line. Keeping a possibility of ascites and pleural effusion, an abdominal sonogram was performed, timely glove drain insertion was ensured, and umbilical lines were removed. The neonate improved dramatically and underwent CDH patch repair. Given the likely distorted vascular anatomy, this case underscores the need to re-examine the umbilical venous line insertion practice on the first day in CDH neonates.

Diagnosis and Management of Hepatic Hydrothorax.

Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In most cases, hepatic hydrothorax is seen in patients with ascites. However, ascites is not always found at diagnosis and is not clinically detected in 20% of patients with hepatic hydrothorax. Some patients have no symptoms and incidental findings on radiologic examination lead to the diagnosis of the condition. In the majority of cases, the patients present with symptoms such as dyspnea at rest, cough, nausea, and pleuritic chest pain. The diagnosis of hepatic hydrothorax is based on clinical manifestations, radiological features, and thoracocentesis to exclude other etiologies such as infection (parapneumonic effusion, tuberculosis), malignancy (lymphoma, adenocarcinoma) and chylothorax. The management strategy involves a stepwise approach of one or more of the following: Reducing ascitic fluid production, preventing fluid transfer to the pleural space, fluid drainage from the pleural cavity, pleurodesis (obliteration of the pleural cavity), and liver transplantation. The complications of hepatic hydrothorax are associated with significant morbidity and mortality. The complication that causes the highest morbidity and mortality is spontaneous bacterial empyema (also called spontaneous bacterial pleuritis).

Recent developments in the management of ascites in cirrhosis.

In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long-term albumin infusion may improve survival in patients with cirrhosis and ascites while beta-blockers may reduce ascites occurrence. Transjugular intrahepatic porto-systemic shunt (TIPS) placement may also improve survival in selected patients in addition to the control with ascites. Low-flow ascites pump insertion can be another option for some patients with intractable ascites. In this review, we summarize the latest data related to the management of ascites occurring in cirrhosis. There are still unanswered questions, such as the optimal use of albumin as a long-term therapy, the place of beta-blockers, and the best timing for TIPS placement to improve the natural history of ascites, as well as the optimal stent diameter to reduce the risk of shunt-related side-effects. These issued should be addressed in future studies.

Left hepatic hydrothorax without ascites.

Hepatic hydrothorax (HH) is a complication in patients with cirrhosis and portal hypertension. It predominantly presents in the right pleural cavity and usually associates with ascites. Few cases of HH occurring without detectable ascites have been reported. This case report comprehensively presents a case of a refractory left unilateral HH without ascites. The patient benefited from palliative care and the HH was managed using a semipermanent indwelling pleural catheter until she died 3 months after diagnosis.

[A Case of Concentrated Ascites Reinfusion Therapy(CART)for Abundant Refractory Ascites in Cecal Cancer with Peritoneal Dissemination Followed by the Readministration of Chemotherapy].

A 66-year-old man underwent laparoscopic ileocecal resection for cecal cancer with liver metastasis(cT3N1M1a, cStage Ⅳa). One month later, combination chemotherapy with capecitabine, oxaliplatin, and bevacizumab was administered for liver metastasis. However, during the treatment, peritoneal dissemination and abundant diuretic-resistant ascites was revealed, resulting in poor dietary intake. One year and 11 months after the surgery, the chemotherapy was interrupted and cell-free and concentrated ascites reinfusion therapy(CART)was undergone as palliative care. The initial volume of retrieved ascites was 6,500 mL, and the volume was increased gradually to a maximum of 14,020 mL without hemodynamic instability. Totally CART was administered 10 times during 7 months without any complications: mean volume of retrieved ascites; 9,780 mL/unit, the interval between therapies; 2-3 weeks. Serum albumin level did not decrease since CART administration. His oral intake and daily activities were improved by CART. These clinical outcomes contributed to the readministration of chemotherapy. We present a recent case of safe and periodical CART for abundant refractory ascites in cecal cancer with peritoneal dissemination, resulting in the improvement of QOL and the readministration of chemotherapy.

Successful treatment of refractory ascites in a patient with liver cirrhosis combined with hepatic artery-portal vein malformation: A case report.

INTRODUCTION: Hepatic artery-portal vein malformation is rarely encountered in clinical practice. Here, we reported a case of liver cirrhosis combined with hepatic artery-portal vein malformation with refractory ascites as the main symptom. And it was successfully treated by us. The present case demonstrates the role of hepatic artery-portal vein malformation in cirrhotic ascites and the importance of early diagnosis and interventional treatment. This article may provides some experience for the treatment of such patients. PATIENT CONCERNS: The patient was a 72-year-old woman with a 40-year history of Hepatitis B virus surface antigen positivity who sought medical advice with a chief complaint of abdominal distension for 1 week. DIAGNOSES: Enhanced abdominal computed tomography imaging of this patient revealed liver cirrhosis, splenomegaly, esophageal and gastric varices, massive ascites, and a low-density area in the S4 segment of the liver with an ambiguous boundary. Widening of the left branch of the portal vein was evident, and the portal vein was highlighted in the arterial phase and the venous phase. Digital subtraction angiography revealed substantial thickening of the left hepatic artery, and the administered contrast agent drained through the malformed vascular mass to the thickened left portal vein. Liver cirrhosis combined with hepatic artery-portal vein malformation were diagnosed. And we considered that the artery-portal vein malformation in this patient might be caused by cirrhosis. INTERVENTIONS: The patient was applied diuretics, entecavir and transcatheter embolization. OUTCOMES: The patient ascites did not resolve significantly when treated with diuretics alone. After the transcatheter embolization, the patient ascites relieved remarkably. CONCLUSION: The patient underwent transcatheter embolization for hepatic artery-portal vein malformation, after which her ascites resolved with good short-term curative efficacy. So, the patients who suffered from liver cirrhosis combined with hepatic artery-portal vein malformation and refractory ascites, should be active on transcatheter embolization.

Advances in the treatment of malignant ascites in China.

PURPOSE: Malignant ascites (MA) often occurs in recurrent abdominal malignant tumors, and the large amount of ascites associated with cancerous peritonitis not only leads to severe abdominal distension and breathing difficulties, but also reduces the patient's quality of life and ability to resist diseases, which usually makes it difficult to carry out anti-cancer treatment. The exploration of MA treatment methods is also a key link in MA treatment. This article is going to review the treatment of MA, to provide details for further research on the treatment of MA, and to provide some guidance for the clinical treatment of MA. METHOD: This review analyzes various expert papers and summarizes them to obtain the paper. RESULT: There are various treatment methods for MA, including systemic therapy and local therapy. Among them, systemic therapy includes diuretic therapy, chemotherapy, immunotherapy, targeted therapy, anti angiogenic therapy, CAR-T, and vaccine. Local therapy includes puncture surgery, peritoneal vein shunt surgery, acellular ascites infusion therapy, radioactive nuclide intraperitoneal injection therapy, tunnel catheter, and intraperitoneal hyperthermia chemotherapy. And traditional Chinese medicine treatment has also played a role in enhancing efficacy and reducing toxicity to a certain extent. CONCLUSION: Although there has been significant progress in the treatment of MA, it is still one of the clinical difficulties. Exploring the combination or method of drugs with the best therapeutic effect and the least adverse reactions to control MA is still an urgent problem to be solved.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

The Impact of a Point-of-Care Ultrasound (POCUS) Program to Diagnose and Manage Ascites in Home-based Palliative Care.

OBJECTIVE: The objective of this study was to examine the impact of a point-of-care ultrasound (POCUS) program among people with ascites receiving home-based palliative care by measuring the association of POCUS with ascites-related days spent out of the home, compared with outcomes before POCUS implementation. DESIGN: Open cohort study. SETTING AND PARTICIPANTS: Adults who had an ascites-related procedure (ARP) between January 1, 2014, and December 31, 2015 (ie, pre-POCUS) and January 1, 2019, and December 31, 2020 (ie, POCUS). An ARP was defined as using ultrasound to diagnose suspected ascites or a paracentesis with or without ultrasound guidance to manage ascites. METHODS: The main outcome was the rate of ascites-related days spent out of the home, defined as days out of the home for either ARPs or because of ascites-related hospital admissions, relative to the time patients were at risk for spending ascites-related days out of the home. RESULTS: Among the 103 pre-POCUS patients (mean age 68.0; 50.4% female), there were 161 ARPs with 12.4% occurring at home. Among the 127 POCUS patients (mean age 74.0; 52.0% female) there were 193 ARPs with 82.4% occurring at home. POCUS was associated with a significantly lower rate of ascites-related days spent outside the home (pre-POCUS rate of 33 days per 1000 patient days vs POCUS rate of 9 days; unadjusted incidence rate ratio (IRR), 3.86; 95% CI, 2.95-5.12; P < .001; adjusted IRR, 3.83; 95% CI, 1.27-11.54; P = .02). POCUS was also associated with a higher likelihood of ARPs occurring in the home [unadjusted odds ratio (OR), 32.44; 95% CI, 18.15-59.90; P < .001; adjusted OR, 48.99; 95% CI, 21.04-114.10; P < .001]. CONCLUSIONS AND IMPLICATIONS: The use of POCUS may contribute to maximizing time spent at home for palliative care patients with ascites. These findings support the use of POCUS for home-based palliative care programs.

Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Ascites and Chronic Liver Disease in Children.

Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of mortality. A diagnostic paracentesis should be performed in liver disease patients with- new-onset ascites, at the beginning of each hospital admission and when ascitic fluid infection (AFI) is suspected. The routine analysis includes cell count with differential, bacterial culture, ascitic fluid total protein and albumin. A serum albumin-ascitic fluid albumin gradient of ≥1.1 g/dL confirms the diagnosis of portal hypertension. Ascites has been reported in children with non-cirrhotic liver disease like acute viral hepatitis, acute liver failure and extrahepatic portal venous obstruction. The main steps in management of cirrhotic ascites include dietary sodium restriction, diuretics and large-volume paracentesis. Sodium should be restricted to maximum of 2 mEq/kg/d (max 90 mEq/d) of sodium/day. Oral diuretic therapy comprises of aldosterone antagonists (e.g., spironolactone) with or without loop-diuretics (e.g., furosemide). Once the ascites is mobilized, the diuretics should be gradually tapered to the minimum effective dosage. Tense ascites should be managed with a large-volume paracentesis (LVP) preferably with albumin infusion. Therapeutic options for refractory ascites include recurrent LVP, transjugular intrahepatic porto-systemic shunt and liver transplantation. AFI (fluid neutrophil count ≥250/mm3) is an important complication, and requires prompt antibiotic therapy. Hyponatremia, acute kidney injury, hepatic hydrothorax and hernias are the other complications.

Prospective comparison between a peristaltic pump and vacuum containers for paracentesis: Time, resources and safety.

RATIONALE AND OBJECTIVES: To meet the increasing demand for radiology departments to perform paracenteses, this study was done to compare the operational, financial and clinical impact of draining ascites with a peristaltic pump versus conventional vacuum containers. MATERIALS & METHODS: Prospective cohort study of 157 paracenteses (56 subjects) drained with ACCEL® evacuated drainage bottles (B. Braun Interventional Systems, Bethlehem, PA) and 159 paracenteses (53 subjects) drained with the RenovaRP® pump (Laborie Medical Technologies Corp., Portsmouth, NH). A short elective questionnaire was then distributed to the procedure staff and the subjects drained by both methods. RESULTS: Mean volume drained with the pump (5 L) was comparable to that drained by vacuum containers (4.9 L, p = 0.77). Mean time to drain subjects with the pump (18.6 min) was 9.1 min shorter and 3.8 min less variable than subjects drained with vacuum containers (27.7 min). This difference was statistically significant (p < 0.01) and clinically important (effect size = 0.73). Flow rate with the pump (4 min/L) was significantly faster (p < 0.05) than vacuum containers flow rate (6.6 min/L). No adverse events occurred in either group. Use of the pump increased the average cost by 21% and reduced earnings by 3%. All assistants (n = 6) and patients (n = 10) that responded to the questionnaire recommended the use of the pump over vacuum containers. CONCLUSION: The peristaltic pump safely drains ascites significantly faster and with less variability in time than vacuum containers. While use of the pump slightly increases cost per paracentesis, it was recommended by all paired subjects undergoing a paracentesis and all personnel assisting in the procedure.

Progress in the treatment of malignant ascites.

Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.

Effect of the Home to Hospital to Home nutrition management program on postoperative liver cancer patients: A single-center randomized controlled study.

BACKGROUND: Malnutrition is the most common complication in postoperative liver cancer patients. This study aimed to investigate the effects of the Home to Hospital to Home nutrition management program on postoperative liver cancer patients. METHODS: A total of 184 liver cancer patients were randomly assigned to either an intervention group (treated under the Home to Hospital to Home nutrition management program) or a control group (treated with the general nutritional method). Nutrition-related indicators, such as prealbumin (PA) and albumin, were assessed before and after treatment in both groups. The incidence of complications (e.g., nausea or vomiting, bloating, difficulty defecating, ascites), length of hospital stay, first time to anal exhaust and out-of-bed activity, and patient satisfaction were recorded. RESULTS: A total of 184 liver cancer patients were randomly assigned to either an intervention group (treated under the Home to Hospital to Home nutrition management program) or a control group (treated with the general nutritional method). Nutrition-related indicators, such as prealbumin (PA) and albumin, were assessed before and after treatment in both groups. The incidence of complications (e.g., nausea or vomiting, bloating, difficulty defecating, ascites), length of hospital stay, first time to anal exhaust and out-of-bed activity, and patient satisfaction were recorded. CONCLUSION: The Home to Hospital to Home nutrition management program improves the nutritional status of postoperative liver cancer patients, lowers the incidence of complications, shortens hospital stays, increases patient satisfaction, and promotes the early recovery of patients.

Managing ascites in patients with cirrhosis.

ABSTRACT: Patients with cirrhosis have a 50% to 60% chance of developing ascites within 10 years of diagnosis. Once ascites has developed, patients have a predicted 50% mortality within 3 years. This article discusses the pathophysiology of ascites caused by cirrhosis, standards in diagnosing ascites, and the recommendations and guidelines for treating ascites. Properly managing patients with decompensated cirrhosis can improve their quality of life and longevity and minimize additional complications.

Acute kidney injury in patients with cirrhosis - practical summary.

Acute kidney injury (AKI) is a relatively common condition in patients with advanced liver disease and which is associated with increased mortality. It mainly affects patients with decompensated cirrhosis, particularly those with advanced portal hypertension and ascites. The dual organ involvement may have different forms. The contributing pathogenetic mechanisms are common and predict a dismal prognosis. Early diagnosis and interventions involving specialists (in particular, hepatologists and nephrologists) are essential to improve outcomes.