Balloon-occluded retrograde transvenous obliteration for treatment of portal hypertensive related varices.

PURPOSE OF REVIEW: Balloon-occluded retrograde transvenous obliteration (BRTO) is becoming a more commonly used procedure to manage various complications of liver disease. It is important to understand the technique of the procedure, the indications for its use, and also potential associated complications. RECENT FINDINGS: BRTO is superior to endoscopic cyanoacrylate injection and transjugular intrahepatic portosystemic shunt for bleeding gastric varices associated with a portosystemic shunt and should be considered a first line therapy in these patients. In addition, it has been shown to be useful in controlling ectopic variceal bleeding, improving portosystemic encephalopathy, and also in modulating blood flow in the post liver transplant setting. Modified versions of BRTO, plug assisted retrograde transvenous obliteration and coil assisted retrograde transvenous obliteration, have been developed to reduce procedure time and improve complication rates. SUMMARY: As the use of BRTO expands in clinical practice it will be important for gastroenterologists and hepatologists to better understand the procedure. There are still many research questions left to answer regarding the use of BRTO in specific situations and for specific patient populations.

Relative adrenal insufficiency in the non-critically ill patient with cirrhosis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non-critically ill patients with cirrhosis. METHODS: A systematic review and meta-analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid-MEDLINE, ScienceDirect, Web of Science, Cochrane Library and ClinicalTrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 µg/dl, delta total cortisol <9 µg/dl or composite of the two thresholds in response either a standard-dose or low-dose short synacthen test. Odds ratios and standardized mean differences from random-effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. RESULTS: Twenty-two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33-42%). The prevalence of RAI varied by Child-Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety-day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69-4.92, I2 = 15%, p < 0.001). CONCLUSIONS: Relative adrenal insufficiency is highly prevalent in non-critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.

Split liver transplantation with extended right grafts on adult recipients: A propensity score matching analysis.

INTRODUCTION: Split liver transplantation (SLT) emerged due to its potential to contribute to the organ pool and reduce organ shortage. However, SLT is technically challenging and has been associated with higher rates of postoperative complications leading to concerns about graft and patient survival. Moreover, there are few studies on matched-pair adult recipients of SLT and whole-liver transplant (WLT), with conflicting results. METHODS: This retrospective study analyze outcomes among adults who underwent SLT at our institution from 2010 to 2019. A 1:1 propensity score matching analysis was performed based on important donor and recipient variables. Baseline characteristics and postoperative outcomes were analyzed and compared between groups. Actuarial graft and patient survival were analyzed by KM curves. RESULTS: Out of 592 adults receiving a LT in our institution, 21 SLT adult recipients were identified and matched with 21 adults undergoing WLT. As expected donor age was significantly lower in SLT recipients (16 (15-22) vs. 32 (17-47), P = .012). Additional donor characteristics, including anthropometrics, and ischemic times were similar between groups. Baseline recipient characteristics and postoperative outcomes, including length of stay, vascular complications, biliary complications, and re-transplantation were comparable between SLT and WLT recipients. Graft (95/95/95 vs. 100/94/94, P = .98) and patient (100/100/100 vs. 100/94/94, P = .30) survival at 1-, 3-, 5-years, were similar between the SLT- and WLT group, respectively. CONCLUSION: Split liver transplantation has the potential to increase the availability of organs for adult recipients without compromising individual outcomes.

AGA Clinical Practice Update on Management of Bleeding Gastric Varices: Expert Review.

Management of bleeding gastric varices (GV) presents a unique challenge for patients with portal hypertension. Despite over thirty years of diagnostic and treatment advances standardized practices for bleeding GV are lacking and unsupported by adequate evidence. There are no definitive natural history studies to help with risk assessment or prospective clinical trials to guide clinical decision making. Available literature on the natural history and management of gastric varices consists of case series, restricted cohort studies, and a few small randomized trials, all of which have significant selection biases. This review summarizes the available data and recommendations based on expert opinion on how best to diagnose and manage bleeding from gastric varices. Table 1 summarizes our recommendations.

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis.

BACKGROUND AND AIMS: Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute. METHODS: We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care centre. Subjects were administered 250 µcg cosyntropin, with RAI defined as an increase in total cortisol <9 µg/dL. High-density lipoprotein (HDL) levels and serum cholesterol esterification percentage (%CE), a validated surrogate marker of lecithin-cholesterol acyltransferase (LCAT) activity, were measured to assess the relationship between disordered cholesterol metabolism and the presence of RAI. Subjects were followed until death, liver transplantation or a maximum of 6 months. RESULTS: Subjects with RAI had decreased levels of HDL (18 vs 29 mg/dL, P < .01) and %CE (64% vs 66%, P = .03). Correlation was seen between HDL and %CE (r = 0.7, R2  = 0.49; P < .01) and each integer decrease in %CE predicted an approximately 2% increase in the probability of RAI. Transplant-free survival was reduced in subjects with RAI at both 6 months (43% vs 71%, P = .01) and 90 days (54% vs 81%, P < .01). CONCLUSIONS: Disruption in cholesterol metabolism contributes to the development of RAI in cirrhosis, as decreased LCAT activity leads to reduced HDL trafficking to the adrenal gland.

Readmissions for Cirrhosis Within the Healthcare Readmissions Reduction Program: A Hidden Challenge.

With the passage of the Affordable Care Act, the Healthcare Readmissions Reduction Program (HRRP) was implemented, leading to significant reductions in readmissions for congestive heart failure, pneumonia, and myocardial infarction. Patients with cirrhosis have a complex and difficult to manage underlying disease process and are often left out of large policy decisions such as the HRRP although they represent a population at high risk for readmission and other negative outcomes. In this editorial, hospital readmissions in patients with cirrhosis are discussed in the context of the HRRP and evolving models of care.

Balloon Retrograde Transvenous Obliteration Versus Endoscopic Cyanoacrylate in Bleeding Gastric Varices: Comparison of Rebleeding and Mortality with Extended Follow-up.

PURPOSE: To assess short- and long-term mortality and rebleeding with endoscopic cyanoacrylate (EC) versus balloon-occluded retrograde transvenous obliteration (BRTO). MATERIALS AND METHODS: A retrospective cohort comparison was conducted of 90 EC patients and 71 BRTO patients from 1997 through 2015 with portal hypertension who presented due to endoscopically confirmed bleeding cardiofundal gastric varices. Patients underwent either endoscopic intra-varix injection of 4-carbon-n-butyl-2-cyanoacrylate or sclerosis with sodium tetradecyl sulfate with balloon occlusion for primary variceal treatment. RESULTS: Seventy-one BRTO patients and 90 EC patients, of whom 89% had cirrhosis and 35% were women, were included, with a respective average Model for End-Stage Liver Disease (MELD) score of 13.4 and 14.4, respectively. Mortality at 6 weeks was 14.4% for EC patients and 13.1% for BRTO patients (Kaplan-Meier/Wilcoxon, P = .85). No long-term mortality difference was observed (Cox hazard ratio [HR] = 0.89, P = .64). Also, 5.1% of EC patients and 3.5% of BRTO patients (Kaplan-Meier/Wilcoxon, P = .62) rebled at 6 weeks, but at 1 year, 22.0% of EC patients and 3.5% of BRTO patients had rebled (Kaplan-Meier/Wilcoxon, P < .01). Lower rates of long-term rebleeding were found with BRTO (Cox HR = 0.25, P = .03). No difference was seen in the rate of new portal hypertensive complications (Cox HR = 1.21, P = .464). However, 16/71 patients who underwent BRTO had simultaneous transjugular intrahepatic portosystemic shunt. Age, sex, MELD score, and presence of cirrhosis were the primary predictors of mortality. One death in the EC group and 5 deaths in the BRTO group were deemed to be procedurally related (chi-square, P = .088). CONCLUSIONS: BRTO is associated with a lower rate of rebleeding but no change in mortality.

Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial.

INTRODUCTION: Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS: Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. RESULTS: Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). DISCUSSION: The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

Editorial: "Lean" NAFLD: Metabolic Obesity with Normal BMI Is It in the Genes?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. "Lean" NAFLD represents a patient subpopulation with hepatic steatosis evident on imaging with normal BMI. This paper by Feldman and Eder et al. illustrates the mild but clear metabolic differences and genetic connections in Caucasian lean NAFLD patients compared with obese NAFLD and healthy controls. Their findings highlight key similarities of lean and obese NAFLD compared with lean healthy subjects. This paper characterizes "lean" NAFLD as a unique phenotype with specific genetic associations deserving of further investigation in the greater scheme of elucidating the pathophysiology of fatty liver.

Portal vein thrombosis: When to treat and how?

Portal vein thrombosis is an unusual thrombotic condition not frequently seen in the general population; however, it has a higher prevalence in special circumstances such as in liver cirrhosis and hepatic or pancreatic malignancy. It also can be associated with significant morbidity and mortality. In this review, we discuss the current data available to guide therapy in the setting of different associated co-morbidities, hypercoagulable states, and associated thrombosis of the remaining splanchnic circulation. We discuss indications for anticoagulation, including the choice of anticoagulants, as well as the role of conservative 'wait and watch' and invasive therapies, such as thrombolysis, thrombectomy, and transjugular intrahepatic portosystemic shunt.

Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding.

BACKGROUND: Hospitalized patients with cirrhosis are at risk to develop venous thromboembolism. Although current guidelines support the routine administration of thromboprophylaxis to hospitalized patients, there is limited data regarding the safety or efficacy of this practice in hospitalized cirrhosis patients. AIMS: We aimed to determine if administration of thromboprophylaxis was associated with increased complication rates for hospitalized cirrhosis patients. METHODS: Data were collected on patients admitted to the University of Virginia between 2007 and 2010. Study personnel systematically collected data on complications, including gastrointestinal bleed, venous thromboembolism and death directly from the medical record. RESULTS: A total of 235 patients (accounting for 355 discrete hospitalizations in which thromboprophylaxis was administered) met inclusion criteria accounting for 1660 person-days of thromboprophylaxis administered to patients. The mean age at admission was 58 (95% CI 57.1-59.2) years and 217 (61%) were male patients. The mean admission model for end-stage liver disease (MELD) score was 16.2 (95% CI 15.5-16.9). The mean hospital length of stay was 6.5 (95% CI 5.9-7.4) days. In patients who received thromboprophylaxis, the mean treatment length was 4.7 days (95% CI 4.2-5.2). There were nine gastrointestinal bleeding events (2.5% of admissions), five venous thromboembolisms (1.4% of admissions), two cases of heparin-induced thrombocytopenia (0.5% of admissions) and 14 deaths overall (3.9% of admissions). CONCLUSIONS: The use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.

Endoscopic Treatment of Acute Esophageal and Gastric Variceal Bleeding.

Acute variceal bleeding is a serious complication of portal hypertension. This most often manifests as bleeding from esophageal varices. Although less likely to occur, bleeding from gastric varices is usually more severe. The best endoscopic management for acute esophageal variceal bleeding is band ligation and this often proves to be definitive therapy for these patients. For gastric variceal bleeding, the best endoscopic therapy is endoscopic cyanoacrylate injection but this can be cumbersome to perform and is not a readily available resource at most centers in the United States.

Basal cortisol levels do not predict adrenal responsiveness in acute decompensated cirrhosis.

OBJECTIVE: Morning total cortisol (TC) levels have been shown to predict adrenal dysfunction (AD) in the general population, but their utility in cirrhosis is unknown. METHODS: A retrospective cohort study was performed including all noncritically ill patients at our institution between 2011 and 2022 admitted with acute decompensated cirrhosis who underwent standard-dose adrenocorticotropic hormone (ACTH) stimulation testing. Adrenal dysfunction was defined as an increase in TC (delta TC) level <9 µg/dl 60 minutes after ACTH dosing. Spearman correlation was utilized to assess the relationship between binding globulins and cortisol levels. Multivariate regression analysis was performed to determine if basal TC level or common clinical parameters were predictive of AD. RESULTS: One hundred and nineteen patients were included, with a median model for end-stage liver disease score of 18. Albumin levels did not correlate with basal TC levels (ρ = 0.127; P = 0.169); basal TC did not correlate with delta TC (ρ = 0.050; P = 0.591). The degree of hypoalbuminemia did not alter these relationships. On multivariate regression, only albumin level [odds ratio (OR) = 0.418; 95% confidence interval (CI), 0.196-0.890; P = 0.024] and MELD score (OR, 1.094; 95% CI, 1.019-1.174; P = 0.014) were predictive of AD. Basal TC levels were not predictive of AD (OR = 0.991; 95% CI, 0.903-1.088; P = 0.855) or delta TC (ß = 0.000; 95% CI -0.147 to 0.147; P = 0.999). CONCLUSION: Baseline TC levels do not predict ACTH stimulation testing response in patients with acute decompensated cirrhosis. Clinicians should avoid utilizing an isolated morning cortisol result as a screening method for AD in this population.

Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth the trouble.

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12 mm Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.