Beta-blockers and physical frailty in patients with end-stage liver disease.

AIM: To investigate beta-blocker (BB) use in patients with cirrhosis and determine their effects on physical frailty and overall survival. METHODS: Adult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for transplant. RESULTS: Of 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female (25% vs 46%; P < 0.001) and BMI (29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty (by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality (SHR 0.55; P = 0.005). CONCLUSION: In patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated.

Primary biliary cholangitis: new treatments for an old disease.

Primary biliary cholangitis (PBC) is an immunological condition that causes a significant health disturbance and dramatically reduces the quality of life for those affected with the disease. It is a potentially fatal disease that can lead to multiple hepatic and extrahepatic complications. Having adequate therapeutic interventions that can improve the course of the disease is imperative in reducing the associated morbidity and mortality. Ursodeoxycholic acid (UDCA) is the gold standard therapy. However, it has been associated with suboptimal response rates in a significant proportion of patients. Despite UDCA, approximately 35%-40% of individuals with PBC still experience a progression of the disease, leading to liver failure and requiring liver transplantation. Recent studies of new pharmacological approaches have shown beneficial outcomes. Some of these agents can now be applied to a clinical scenario. In this review article, we will outline the new and emerging treatments for PBC.

Management of Pruritus in Primary Biliary Cholangitis: A Narrative Review.

Primary biliary cholangitis is an autoimmune condition characterized by destruction of intrahepatic bile ducts. It causes debilitating symptoms that dramatically affect the patient's quality of life. Pruritus affects 60% to 70% of individuals with primary biliary cholangitis and leads to sleep disturbances, fatigue, depression, and suicidal ideation. A complete search was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, Countway Library, and CINAHL with specific search terms. This narrative review was prepared after a comprehensive literature review. Treating patients with cholestatic pruritus is challenging and may have a profound impact on quality of life. The standard of therapy for primary biliary cholangitis, ursodeoxycholic acid, does not have a beneficial effect in cholestatic pruritus. Patients often do not respond to conventional therapies such as cholestyramine, rifampicin, opioid antagonists, and sertraline. These therapies lack long-term efficacy and have side effects. Patients who have not responded to these initial treatments can be considered for experimental therapies or clinical trials. This review outlines the current and emerging treatment modalities for patients with primary biliary cholangitis who have pruritus.

The Changing Role of Sodium Management in Cirrhosis.

OPINION STATEMENT: Hyponatremia may occur in patients with cirrhosis and ascites mainly due to water retention and an inability of the kidney to excrete free water. The main reason for this abnormality is related to the fact that these patients have portal hypertension and this leads to systemic vasodilation that in turn activates sodium-retaining and water-retaining systems such as the renin-angiotensin-aldosterone system and arginine vasopressin (AVP). AVP increases solute-free water retention by acting on the V2 receptors of the kidney-collecting tubes. Hyponatremia in cirrhosis is defined as a serum sodium level less than 130 meq/L. The appearance of hyponatremia in patients with advanced cirrhosis portends a poor prognosis before and after liver transplantation. Treatment of hyponatremia is difficult; fluid restriction rarely increases serum sodium levels and other therapies are associated with important drawbacks. A thorough discussion of the underlying mechanisms leading to hyponatremia and hypernatremia in cirrhosis and current treatment options including the use of vaptans (V2 receptor antagonists) are discussed in this review.

Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction.

BACKGROUND & AIMS: Current clinical assays for total 25-hydroxy (OH) vitamin D measure vitamin D bound to vitamin D-binding protein (DBP) and albumin plus unbound ('free') D. We investigated the relationship between total and free 25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (≤3.5 g/dl) albumin cirrhotics. METHODS: Eighty-two cirrhotics underwent measurement of free and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact parathyroid hormone (iPTH), C-telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), osteocalcin, amino-terminal pro-peptide of type 1-collagen (P1NP)]. Pearson's coefficients assessed relevant associations. RESULTS: Cirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3 µg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7 vs. 24.8 µg/L) were increased (P < 0.01). An inverse relationship was observed between total 25(OH)D and iPTH in normal (r = -0.47, P = 0.01) but not low albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between free 25(OH)D and iPTH(Normal: r = -0.46, P = 0.01; Low: r = -0.03, P = 0.84). BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics but not consistently associated with total or free 25(OH)D. CONCLUSIONS: Cirrhotics with low vs. normal albumin have lower levels of DBP, total and free 25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was observed in normal but not in low albumin cirrhotics, demonstrating that total 25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics with synthetic dysfunction. Additional investigation into the role of vitamin D supplementation and its impact on bone mineral homoeostasis in this population is needed.

Clinician assessments of health status predict mortality in patients with end-stage liver disease awaiting liver transplantation.

BACKGROUND & AIMS: The US liver allocation system effectively prioritizes most liver transplant candidates by disease severity as assessed by the Model for End-Stage Liver Disease (MELD) score. Yet, one in five dies on the wait-list. We aimed to determine whether clinician assessments of health status could identify this subgroup of patients at higher risk for wait-list mortality. METHODS: From 2012-2013, clinicians of all adult liver transplant candidates with laboratory MELD≥12 were asked at the clinic visit: 'How would you rate your patient's overall health today (0 = excellent, 5 = very poor)?' The odds of death/delisting for being too sick for the transplant by clinician-assessment score ≥3 vs. <3 were assessed by logistic regression. RESULTS: Three hundred and forty-seven liver transplant candidates (36% female) had a mean follow-up of 13 months. Men differed from women by disease aetiology (<0.01) but were similar in age and markers of liver disease severity (P > 0.05). Mean clinician assessment differed between men and women (2.3 vs. 2.6; P = 0.02). The association between clinician-assessment and MELD was ρ = 0.28 (P < 0.01). 53/347 (15%) died/were delisted. In univariable analysis, a clinician-assessment score ≥ 3 was associated with increased odds of death/delisting (2.57; 95% CI 1.42-4.66). After adjustment for MELD and age, a clinician-assessment score ≥ 3 was associated with 2.25 (95% CI 1.22-4.15) times the odds of death/delisting compared to a clinician-assessment score < 3. CONCLUSIONS: A standardized clinician assessment of health status can identify liver transplant candidates at high risk for wait-list mortality independent of MELD score. Objectifying this 'eyeball test' may inform interventions targeted at this vulnerable subgroup to optimize wait-list outcomes.

Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C.

BACKGROUND: Whether chronic HCV, a disease characterized by systemic inflammation, impacts bone mineral density (BMD) independent of cirrhosis is unknown. AIM: We aimed to evaluate the association between BMD, systemic inflammation, and markers of bone turnover in chronic HCV without cirrhosis. METHODS: Non-cirrhotics, 40-60 years old, with chronic HCV underwent measurement of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of systemic inflammation and bone turnover. By Chi-squared or t test, we compared those with normal versus low BMD. RESULTS: Of the 60 non-cirrhotics, 53 % were female and 53 % Caucasian. Mean (SD) age was 53.3 years (5.7), total bilirubin 0.7 mg/dL (0.3), creatinine 0.8 mg/dL (0.2), and body mass index 28.4 kg/m(2) (6.5). Low BMD was observed in 42 %: 30 % had osteopenia, 12 % had osteoporosis. Elevated tumor necrosis factor α, interleukin-6, and C-reactive protein levels were found in 26, 32, and 5 %, respectively, but did not differ by BMD group (p > 0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5 mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5 ng/mL) [p < 0.05], but similar bone-specific alkaline phosphatase, serum C-telopeptide, and parathyroid hormone levels. CONCLUSIONS: Low BMD is prevalent in 40- to 60-year-old non-cirrhotics with chronic HCV, but not associated with systemic inflammatory markers. Elevated P1NP levels may help to identify those at increased risk of bone complications in this population. Chronic HCV should be considered a risk factor for bone loss, prompting earlier BMD assessments in both men and women.