Geographic disparities in access to liver transplant for advanced cirrhosis: Time to ring the alarm!

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

Endoscopic ultrasound assessment of gastrointestinal polypoid lesions of indeterminate morphology in patients with portal hypertension.

BACKGROUND AND STUDY AIMS: Polypoid lesions found during upper gastrointestinal endoscopy (UGIE) are occasionally found in patients with portal hypertension (PH). This study aimed to assess the true nature of such polypoid lesions using endoscopic ultrasound (EUS) and determine the accuracy of UGIE in differentiating between vascular and non-vascular lesions in PH. PATIENTS AND METHODS: We retrospectively assessed all patients with PH referred for EUS due to polypoid lesions of unknown nature at UGIE over a 7-year period. Cases of known varices were excluded. UGIE findings were compared to EUS findings. RESULTS: 66 patients were included (26 male). Commonest UGIE findings were: possible varices (19.4 %), polypoid/neoplastic lesion (52.8 %) and submucosal lesion (16.7 %). After EUS, the final diagnoses were: varices in 25 %, polypoid lesion with underlying vessel/varix in 27.8 % and non-vascular lesion or submucosal lesion in 47.2 %. The diagnostic accuracy of UGIE was suboptimal, since 28.6 % of possible varices were eventually found to be non-vascular, while 15.8 % of polyp/neoplastic looking lesions proved to be varices and 42.1 % were lesions with underlying vessel/varix. 50 % of submucosal lesions were eventually found to be varices. CONCLUSION: Endoscopists should have a high index of suspicion of varices or polyps related to varices when assessing atypical looking polypoid lesions in patients with PH. In such cases EUS should be considered before obtaining biopsies.

Inpatient hospital burden of hepatitis C-diagnosed patients with decompensated cirrhosis.

BACKGROUND & AIMS: To describe the burden on inpatient hospital resources over time from patients diagnosed with hepatitis C virus (HCV) infection and who have reached the decompensated stage of cirrhosis (DC), as existing estimates of hospital stay in these patients are limited. METHODS: A retrospective longitudinal dataset was formed via record-linkage between the national HCV diagnosis database and inpatient/daycase hospitalisation and death registers in Scotland. The study population consisted of HCV-diagnosed patients with a first DC admission in 1996-2013, with follow-up available until 31 May 2014. We investigated and quantified the mean cumulative length of hospital stay, distributions over discharge diagnosis categories, and trends in admission rates. RESULTS: Among our study population (n = 1543), we identified 10 179 admissions with any diagnosis post-first DC admission. Between 1996 and 2013 there was a 16-fold rise in annual total admissions (from 112 to 1791) and an 11-fold rise in hospital stay (719-8045). When restricting minimum possible follow-up to 2 years, DC patients (n = 1312) had an overall admission rate of 7.3 per person-year, and spent on average 43 days (26 days during first 6 months) in hospital; for all liver-related, liver-related other than HCC/DC, and non-liver related only admissions, this was 39, 14, and 5 days respectively. CONCLUSIONS: HCV-infected DC patients impose a considerable inpatient hospital burden, mostly from DC- and other liver-related admissions, but also from admissions associated with non-liver comorbidities. Estimates will be useful for monitoring the impact of prevention and treatment, and for computing the cost-effectiveness of new therapies.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study.

BACKGROUND & AIMS: The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. METHODS: HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. RESULTS: Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. CONCLUSIONS: Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. LAY SUMMARY: The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal Hypertension by Phase-Contrast Magnetic Resonance Angiography.

A significant unmet need exists for accurate, reproducible, noninvasive diagnostic tools to assess and monitor portal hypertension (PHT). We report the first use of quantitative MRI markers for the haemodynamic assessment of nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility study in 22 adult patients with PHT and a clinical indication for NSBB, we acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra-abdominal vessels. T1 mapping of liver and spleen was undertaken to assess changes in tissue composition. Target NSBB dose was achieved in 82%. There was a substantial reduction from baseline in mean average flow in the superior abdominal aorta after 4 weeks of NSBB therapy (4.49 ± 0.98 versus 3.82 ± 0.86 L/min, P = 0.03) but there were no statistically significant differences in flow in any other vessels, even in patients with >25% decrease in heart rate (47% of patients). Mean percentage change in liver and spleen T1 following NSBB was small and highly variable. In conclusion, PC-MRA was able to detect reduction in cardiac output by NSBB but did not detect significant changes in visceral blood flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632).

The changing face of liver transplantation for acute liver failure: Assessment of current status and implications for future practice.

The etiology and outcomes of acute liver failure (ALF) have changed since the definition of this disease entity in the 1970s. In particular, the role of emergency liver transplantation has evolved over time, with the development of prognostic scoring systems to facilitate listing of appropriate patients, and a better understanding of transplant benefit in patients with ALF. This review examines the changing etiology of ALF, transplant benefit, outcomes following transplantation, and future alternatives to emergency liver transplantation in this devastating condition.

Cardiac and pulmonary issues in LT assessment candidates.

With the incidence of liver disease increasing worldwide, a growing number of patients are being referred for assessment for liver transplant (LT). Unfortunately, the donor pool is not expanding at the same rate, which consequentially results in increasing demand on a finite resource. It is therefore imperative that the candidate who undergoes an LT gets maximal benefit with a resultant maximal increase in life expectancy. This article addresses some of the main cardiac and pulmonary issues that may occur in LT assessment candidates.

Prevalence of coronary artery calcification in patients undergoing assessment for orthotopic liver transplantation.

Patients with advanced liver disease are at increased risk of cardiovascular events, especially following orthotopic liver transplantation (OLT). Coronary artery calcification (CAC) is a novel and independent predictor of cardiovascular risk, but its prevalence and utility in patients with cirrhosis are unknown. The aim of this study was to define the prevalence of CAC and its association with markers of disease severity and standard measures of cardiovascular risk in a large cohort of patients undergoing OLT assessment. A single-center, prospective, observational study of 147 consecutive patients undergoing assessment for OLT was performed. CAC scores were derived with the Agatston method from thoracic computed tomography scans and correlated with cardiovascular risk factors and measures of liver disease severity. There were 101 patients (66 males) with a mean age of 53.2 years; 46 patients were excluded because the CAC score was not reported. The median CAC score was 40 HU (range, 0-3533). Correlations were identified between the CAC score and age (r = 0.477; P < 0.001), male sex (r = 0.262; P = 0.008), family history of cardiovascular disease (r = 0.208; P = 0.036), Framingham risk score (r = 0.621; P < 0.001), Model for End-Stage Liver Disease score (r = 0.221; P = 0.027), systolic blood pressure (r = 0.285; P = 0.004), diastolic blood pressure (r = 0.267; P = 0.007), cytomegalovirus status (r = 0.278; P = 0.005), fasting glucose (r = 0.330; P = 0.001), number of coronary vessels involved (r = 0.899; P < 0.001), and components of the metabolic syndrome (r = 0.226; P = 0.026). After multivariate analysis, age, systolic blood pressure, fasting glucose, number of features of metabolic syndrome, and number of vessels involved remained significantly associated with CAC. In conclusion, this study identified a high prevalence of occult coronary artery disease in patients undergoing OLT assessment and identified a strong relationship between CAC scores and a limited number of specific cardiovascular risk factors. The usefulness of these factors in predicting perioperative and postoperative cardiovascular events in patients undergoing OLT requires prospective evaluation.