Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database.

INTRODUCTION: We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial. METHODS: The normalization rate of baseline hyponatremia and the 18-month incidence rate of at least moderate hyponatremia were evaluated. RESULTS: The hyponatremia normalization rate was higher with albumin than with standard medical treatment (45% vs 28%, P = 0.042 at 1 month). Long-term albumin ensured a lower incidence of at least moderate hyponatremia than standard medical treatment (incidence rate ratio: 0.245 [CI 0.167-0.359], P < 0.001). DISCUSSION: Long-term albumin administration improves hyponatremia and reduces episodes of at least moderate hyponatremia in outpatients with cirrhosis and ascites.

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites.

BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

The present profile of chronic hepatitis B virus infection highlights future challenges: An analysis of the Multicenter Italian MASTER-B cohort.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a primary cause of morbidity and mortality worldwide. AIM: The study is aimed at updating the clinical and epidemiological profile of chronic HBV infection in Italy. METHODS: A cross-sectional multicenter prospective study enrolled consecutive HBsAg positive patients seen in 73 Italian centers in the period 2012-2015. Individual patient data were collected using an electronic platform and analyzed using standard statistical methods. RESULTS: Among 2877 HBsAg positive individuals (median age 49.8 years, 68% males), 27% were non-Italian natives (NINs); 20% had chronic infection, 58.5% chronic hepatitis and 21.5% cirrhosis. Among NINs, age was younger, male gender was less prevalent and liver disease less advanced than in Italians (all p < 0.0001). HBeAg positive cases were 23.6% among NINs vs 8.2% in Italians (p < 0.0001); HDV coinfections 11.1% vs 7.3% (p = 0.006) and HCV coinfections 2.3% vs 4.2% (p = 0.017), respectively. Anti-HDV or anti-HCV antibodies were detected more frequently in patients with cirrhosis. Fifty percent of NINs with cirrhosis were aged below 45 years. CONCLUSION: The study offers an insight into the evolving burden of chronic hepatitis B virus infection in the near future and highlights new territories for public health interventions.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.

What to start with in first line treatment of chronic hepatitis B patients: an Italian multicentre observational cohort, HBV-RER study group.

Treatment options for chronic hepatitis B (CHB) are pegylated interferon (Peg-IFN) in minimal-mild liver fibrosis and nucleot(s)ide analogues (NUC) in more advanced disease. Since little is known about their use in daily clinical practice, we conducted a multicentre prospective study to investigate treatment regimens applied to naïve CHB patients in real life. HBV-RER is an observational multicentre Italian network that collect clinic and virologic data of patients with CHB. Among the 2527 CHB patients seen during the study period (2009 - 2012), 502 patients started a first line antiviral treatment. Liver biopsy was performed in 30.9% of the patients, with high levels of fibrosis being detected in 19.4% of them. In 216 patients (43%) Peg-IFN was used as first-line therapy while the remaining patients started NUC therapy (entecavir and tenofovir in 75%, lamivudine in 15%, telbivudine and adefovir 10%). By multivariate logistic regression, an age under 40 (OR 0.92, 95%IC 0.90-0.94; p <0.001) and the execution of liver biopsy (OR 3.83; 95%IQR 1.76-8.36; p <0.001) were the only determinants of choice between Peg-IFN vs NUC. Peg-IFN was expected to be used in first-line treatment for CHB in 70% of the patients based on Italian recommendations, but a much lower proportion of patients were actually treated with Peg-IFN with a limited use of the biopsy. Thus, in daily clinical practice physicians prefer to use NUCs, presumably because of their optimal tolerability and anti-viral efficacy, even if they frequently require life-long treatment as opposed to the short duration of Peg-IFN.