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.

External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: A multicenter cohort study.

Several staging systems for hepatocellular carcinoma (HCC) have been developed. The Barcelona Clinic Liver Cancer staging system is considered the best in predicting survival, although limitations have emerged. Recently, the Italian Liver Cancer (ITA.LI.CA) prognostic system, integrating ITA.LI.CA tumor staging (stages 0, A, B1-3, C) with the Child-Turcotte-Pugh score, Eastern Cooperative Oncology Group performance status, and alpha-fetoprotein with a strong ability to predict survival, was proposed. The aim of our study was to provide an external validation of the ITA.LI.CA system in an independent real-life occidental cohort of HCCs. From September 2008 to April 2016, 1,508 patients with cirrhosis and incident HCC were consecutively enrolled in 27 Italian institutions. Clinical, tumor, and treatment-related variables were collected, and patients were stratified according to scores of the Barcelona Clinic Liver Cancer system, ITA.LI.CA prognostic system, Hong Kong Liver Cancer system, Cancer of the Liver Italian Program, Japanese Integrated System, and model to estimate survival in ambulatory patients with hepatocellular carcinoma. Harrell's C-index, Akaike information criterion, and likelihood-ratio test were used to compare the predictive ability of the different systems. A subgroup analysis for treatment category (curative versus palliative) was performed. Median follow-up was 44 months (interquartile range, 23-63 months), and median overall survival was 34 months (interquartile range, 13-82 months). Median age was 71 years, and patients were mainly male individuals and hepatitis C virus carriers. According to ITA.LI.CA tumor staging, 246 patients were in stage 0, 472 were in stage A, 657 were in stages B1/3, and 133 were in stage C. The ITA.LI.CA prognostic system showed the best discriminatory ability (C-index = 0.77) and monotonicity of gradients compared to other systems, and its superiority was also confirmed after stratification for treatment strategy. CONCLUSION: This is the first study that independently validated the ITA.LI.CA prognostic system in a large cohort of Western patients with incident HCCs. The ITA.LI.CA system performed better than other multidimensional prognostic systems, even after stratification by curative or palliative treatment. This new system appears to be particularly useful for predicting individual HCC prognosis in clinical practice. (Hepatology 2018;67:2215-2225).

Entheseal involvement in asymptomatic human immunodeficiency virus infected patients: preliminary results of a clinical and ultrasonographic study.

OBJECTIVES: As a strong association between human immunodeficiency virus (HIV) infection and spondyloarthritis (SpA) has been hypothesised, our main objective was to explore by power Doppler ultrasonography (PDUS) the presence of subclinical enthesitis in asymptomatic HIV patients. The presence of subclinical synovitis was also evaluated. METHODS: Consecutive asymptomatic HIV patients were studied and compared with asymptomatic HCV patients and healthy controls (HC). All subjects underwent a clinical and PDUS bilateral examination of the following entheses and joints: epicondyle, quadriceps, patellar, Achilles and plantar fascia; wrists, II and III metacarpo-phalangeal, knee and ankle. RESULTS: Twenty-nine HIV, 32 HCV and 25 HC were recruited; 1.032 entheses and 860 joints were examined. Clinical diagnosis of enthesitis was made in 10.3% HIV patients, 6.2% HCV patients (p=0.66) and none HC (p=0.24). PDUS enthesitis was found in 72.4% HIV, 28.1% HCV (p=0.0008) and 12% HC (p<0.0001). Clinical diagnosis of synovitis was made in 3.4% HIV patients, 9.3% HCV patients (p=0.61) and none HC (p=1). PDUS abnormalities were documented in 24.1% HIV patients, 71.8% HCV patients (p=0.0003) and none HC (p=0.0001). In detecting enthesitis and synovitis, PDUS was more sensitive than clinical examination both in HIV and HCV patients. CONCLUSIONS: Our preliminary study shows the high frequency of PDUS enthesitis in asymptomatic HIV patients, which highlights the close link between HIV and SpA. Further studies are desirable on a larger number of HIV patients to confirm these results. PDUS proved to be more sensitive than clinical examination in detecting subclinical involvement of entheses and joints.

The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study.

BACKGROUND & AIMS: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation. RESULTS: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death. CONCLUSIONS: Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.

Management and prognosis of hepatocellular carcinoma in the elderly: Results of an in-field multicenter cohort study.

AIMS: This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice. MATERIAL & METHODS: From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non-elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group. Survival differences were measured by unadjusted and adjusted (by inverse probability weight) survival analysis. RESULTS: Elderly patients were mainly females, hepatitis C virus infected and with better conserved liver function (P<.001). At presentation, HCC median size was similar in both groups while, in youngers, HCC was more frequently multinodular (P=.001), and associated with neoplastic thrombosis (P=.009). Adjusted survival analysis showed that age did not predict short-mid-term survival (within 24 months), while it was a significant independent predictor of long-term survival. Moreover, age had a significant long-term survival impact mainly on early HCC stages (Barcelona Clinic for Liver Cancer [BCLC] 0-A), its impact on BCLC B stage was lower, while it was negligible for advanced-terminal stages. CONCLUSIONS: Age per se does not impact on short-mid-term prognosis (≤24 months) of HCC patients, and should not represent a limitation to its management.

Diagnosis, treatment and survival of patients with hepatorenal syndrome: a survey on daily medical practice.

BACKGROUND & AIMS: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis with ascites. The International Ascites Club recommended strict diagnostic criteria and treatment with vasoconstrictors and albumin. Aim of this prospective cohort study was to investigate the prevalence of HRS, diagnostic criteria, treatment and 3-month outcome in the daily-clinical-practice. METHODS: Two-hundred-fifty-three patients with cirrhosis and renal failure consecutively admitted to 21 Italian hospitals were recruited. RESULTS: The prevalence of HRS was 45.8% (30% type-1 and 15.8% type-2). In 36% of cases HRS was presumed because not all diagnostic criteria could be fulfilled. In 8% of cases HRS was superimposed on an organic nephropathy. Patients with HRS type-1 were younger and showed higher leukocyte count, higher respiratory rates, and worse liver function scores. Sixty-four patients with HRS type-1 received vasoconstrictors (40 terlipressin and 24 midodrine/octreotide). A complete response was obtained in 19 cases (30%) and a partial response in 13 (20%). Age was the only independent predictor of response (p=0.033). Three-month survival of patients with HRS type-1 was 19.7%. Survival was better in patients who responded to therapy. Age (p=0.017), bilirubin (p=0.012), and creatinine increase after diagnostic volume expansion (p=0.02) independently predicted death. The mortality rate was 97% among patients with at least two negative predictors. CONCLUSIONS: The diagnostic criteria of HRS in our daily-clinical-practice could not be completely fulfilled in one third of cases. The treatment with vasoconstrictors and albumin was widely implemented. Mortality was strongly predicted by simple baseline variables.

A randomized trial of induction doses of interferon alone or in combination with ribavirin or ribavirin plus amantadine for treatment of nonresponder patients with chronic hepatitis C.

BACKGROUND: Efficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment. METHODS: The study was designed to have 225 HCV nonresponder patients, but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been randomized to receive interferon-alpha2a (group A, n = 26), interferon-alpha2a plus 15 mg/kg per day of ribavirin (group B, n = 24), or interferon-alpha2a plus ribavirin plus 200 mg/day of amantadine hydrochloride (group C, n = 25). Treatment duration was 48 weeks. The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks. RESULTS: On intention-to-treat, the sustained virological response at 24 weeks of follow-up was 11.5% in group A, 12.5% in group B, and 12% in group C. Therapy was discontinued because of adverse effects in three patients in group A (11.5%), three in group B (12.5%), and two in group C (8%). CONCLUSIONS: Nonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12% if retreated with interferon induction treatment followed by administration of a daily dose. The addition of ribavirin or amantadine did not seem to improve the response rates.

Diagnostic accuracy of a rapid fecal test to confirm H pylori eradication after therapy: prospective comparison with a laboratory stool test.

AIM: To investigate the clinical performances of rapid stool test (ImmunoCard STAT HpSA, Meridian Diagnostic Inc.) in the evaluation of eradication therapy of H pylori and to compare it with a well-known and validated laboratory stool test (Amplified IDEA Hp StAR, Dako). METHODS: Stool samples of 122 patients were evaluated after eradication therapy of H pylori. H pylori status was assessed by 13C-urea breath test (UBT). Stool specimens were tested using either the rapid immunoassay kit or the laboratory immunoassay kit. RESULTS: Forty-three patients were infected and 79 non-infected. Sensitivity and specificity of ImmunoCard STAT and Hp StAR were 58.14% and 76.4%, and 97.47% and 98.73%, respectively (P > 0.05). Overall agreement between the two tests was 92.6% (113 of 122 cases). CONCLUSION: ImmunoCard STAT seems to have rather low performances, and it cannot be regarded as a reliable tool in the post-treatment setting. Also Hp StAR cannot be recommended to confirm H pylori eradication after treatment.

[Surveillance and cost-effectiveness of colonoscopy in asymptomatic increased risk subjects of colorectal cancer: Ferrara experience]. / Sorveglianza con colonscopia e analisi costo-beneficio in soggetti asintomatici ad aumentato rischio di cancro del colon-retto: esperienza nella provincia di Ferrara.

Colorectal cancer represents the second leading cause of cancer deaths in western countries with elevated costs for health service. It's very important to develop screening and surveillance programs for cancer prevention with "cost-effective" means. We present a surveillance program with colonoscopy focused on first degree relatives of CRC patients. Colonoscopy is a "cost-effective" mean of screening for high risk subjects.

Hypofractionated stereotactic radiotherapy after transarterial chemoembolisation failure in an unresectable hepatocellular carcinoma: a case presentation.

Introduction. Transarterial chemoembolization is the first-line treatment in unresectable hepatocellular carcinoma. There is no standard treatment after transarterial chemoembolization failure. We report the case of a patient with advanced hepatocellular carcinoma who showed a complete response and a long cancer control with hypofractionated stereotactic radiotherapy after transarterial chemoembolization failure. Case Presentation. A 70-year-old Caucasian woman was treated with transarterial chemoembolization for advanced hepatocellular, but no cancer control was obtained. A hypofractionated stereotactic radiotherapy was planned delivering 40 Gy in 5 fractions. A dramatic reduction in alpha-fetoprotein was observed. Contrast-enhanced ultrasonography at 1 and 2 months showed large necrotic areas. Computerised tomography scan showed a 90% objective tumour response, then a complete remission at 3 and 6 months after treatment, respectively. Status of patient remained unchanged for 2 years. Conclusions. Hypofractionated stereotactic radiotherapy can improve survival and prognosis of unresectable hepatocellular carcinoma patient.

A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C.

BACKGROUND/AIMS: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of chronic hepatitis C. METHODS: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or 18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin for 48 weeks. RESULTS: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40% and 36% for group C and D (P=0.63). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels. CONCLUSIONS: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.