A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

Management of adverse events associated with idelalisib treatment in chronic lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper.

The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib.

Effectiveness and safety of switching to entecavir hepatitis B patients developing kidney dysfunction during tenofovir.

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. METHODS: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFRMDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter. RESULTS: During 46 (4-115) months of ETV treatment, all patients' renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFRMDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFRMDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-R patients (P = 0.018). CONCLUSIONS: Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment.

Liver transplantation for HBV-related cirrhosis in Europe: an ELTR study on evolution and outcomes.

BACKGROUND & AIMS: HBV-related chronic liver disease is one of the most common indications for liver transplantation (LT) in Europe. The ELTR database was used to evaluate outcomes and evolution over 20 years (01/1988 and 12/2010). METHODS: HBV transplanted patients were analysed according to indication for LT: decompensated cirrhosis (HBVdec) or hepatocellular carcinoma (HBV/HCC). These groups were compared with co-infected patients HBV/HDV (HBDV), HBV/HCV (HBCV), HBV/HDV/HCV (HBDCV); n = 16,664 and with HCV patients (n = 2452) according to LT indication. RESULTS: 5912 patients were transplanted for HBV (78% HBVdec, 22% HBV/HCC), with HBV/HCC patients who increased from 15.8% in 1988-1995 to 29.6% in 2006-2010 (p < 0.001). In HBVdec patients, 1, 3, 5, and 10 year patient and graft survival was 83%, 78%, 75%, 68%, and 80%, 74%, 71%, 64%, respectively, significantly better than HBV/HCC (84%, 73%, 68%, 61%, and 81%, 70%, 65%, 58% respectively; p = 0.001 and p = 0.026). In 2006-2010 patient and graft survival significantly improved compared to 1988-1995, both for HBVdec and HBV/HCC (each p < 0.001). A better patient and graft survival was seen in HBV/HCC patients with HBV-DNA(-) compared to HBV-DNA(+) at the time of LT (p < 0.001). Disease recurrence, as cause of death/graft loss, was significantly reduced in recent years compared to the past: currently <1% for HBVdec and 3% for HBV/HCC. CONCLUSIONS: Outcomes of LT for HBV have improved in recent years, with disease recurrence being no longer a significant cause of death/graft loss. HBV-DNA at the time of LT seems to influence survival only in HBV/HCC patients.

Clinical impact of A/H1/N1/09 influenza in patients with cirrhosis: experience from a nosocomial cluster of infection.

A/H1N1/09 influenza is associated with a high risk of complications in patients with chronic diseases, but data on morbidity and mortality in patients with cirrhosis are limited. A cluster of A/H1N1/09 infection in 48 patients admitted to a Gastro-Hepatology Unit is reported. Nosocomial spread, clinical outcome, and viral characteristics of A/H1N1/09 strains from a study group of 48 inpatients (21 and 27 with and without cirrhosis, respectively) were compared with those from a control group of 44 outpatients with mild influenza-like illness and without cirrhosis. A/H1N1/09 infection was confirmed in 8/48 (17%) inpatients. A/H1N1/09 infection rate did not differ in patients with and without cirrhosis (4/21, 19%; 4/27, 15%), but three patients with cirrhosis died of pneumonia and acute respiratory distress syndrome, with fungal or bacterial superinfection in two cases, despite antiviral treatment. None of patients without cirrhosis died. Viral sequences showed the presence of hemagglutinin mutation D222G in two out of three fatal cases and S183P in seven out of eight infected patients. These mutants were not detected in the outpatients group. Even if A/H1N1/09 infection rate in hospitalized patients with and without cirrhosis was not significantly different, cirrhosis and D222G/S183P substitutions were significantly associated with severe disease and poor outcome, also suggesting fungal or bacterial superinfection and portal hypertension as risk factors for A/H1N1/09 disease severity in patients with cirrhosis. Vaccination, preventive and early treatment and a strict control of nosocomial spread should be activated carefully in patients with cirrhosis during epidemics influenza.

Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination.

OBJECTIVES: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. METHODS: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. RESULTS: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. CONCLUSION: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants.

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years.

BACKGROUND & AIMS: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. METHODS: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. RESULTS: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. CONCLUSIONS: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.

Iodide mumps in a patient with liver cirrhosis without renal impairment.

Salivary gland enlargement following iodine-containing contrast media (ICCM), also known as iodide mumps (IM), is a rare condition characterized by swelling of submandibular glands with complete restitutio ad integrum. It manifests itself without pain, fever, dyspnea, rapid heart rate or low blood pressure. The pathogenesis is unknown, it may be an idiosyncratic reaction or toxic due to deposition of iodide in the salivary glands. IM is a condition more frequent in end stage renal disease because of iodine excretion by kidneys but it can also occur in patients without end stage renal disease. In this study, we described a 71-year-old patient with liver cirrhosis due to hepatitis B virus with normal renal function that after administration of ICCM developed IM.

Therapy of Chronic Viral Hepatitis: The Light at the End of the Tunnel?

Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of the viruses. In chronic hepatitis B, long term suppressive treatments with nucleoside/nucleotide analogues have had a dramatic impact on the evolution of liver disease and liver-related complications. However, a conclusive clearance of the virus is difficult to obtain; new strategies that are able to eradicate the infection are currently objects of research. The therapy for Hepatitis D Virus infection is challenging due to the unique virology of the virus, which uses the synthetic machinery of the infected hepatocyte for its own replication and cannot be targeted by conventional antivirals that are active against virus-coded proteins. Recently introduced antivirals, such as bulevertide and lonafarnib, display definite but only partial efficacy in reducing serum HDV-RNA. However, in combination with pegylated interferon, they provide a synergistic therapeutic effect and appear to represent the current best therapy for HDV-positive patients. With the advent of Direct Acting Antiviral Agents (DAAs), a dramatic breakthrough has occurred in the therapeutic scenario of chronic hepatitis C. Cure of HCV infection is achieved in more than 95% of treated patients, irrespective of their baseline liver fibrosis status. Potentially, the goal of global HCV elimination by 2030 as endorsed by the World Health Organization can be obtained if more global subsidised supplies of DAAs are provided.

HBV Reactivation in Patients with Past Infection Affected by Non-Hodgkin Lymphoma and Treated with Anti-CD20 Antibody Based Immuno-Chemotherapy: A Multicenter Experience.

Hepatitis B virus reactivation (HBVr) can develop in HBV surface antigen (HBsAg) positive or HBsAg-negative and anti-hepatitis B core antigen antibodies (anti-HBc) positive (past HBV infection) patients receiving immuno-chemotherapy for hematological malignancies. A higher rate of HBVr is associated with the use of rituximab (R) in patients with past HBV infection, thus justifying an antiviral prophylaxis. In this study we evaluated the incidence of HBVr in a real-life cohort of 362 anti-HBc-positive subjects affected by non-Hodgkin lymphoma (NHL), mainly receiving lamivudine (LAM) prophylaxis (93%) and all undergoing a R-containing regimen. A retrospective, multicenter, observational study was conducted in 4 Italian Hematology Departments. The primary endpoint was the incidence of virologic (HBV DNA-positive), serologic (HBsAg-positive) and clinical (ALT increase > 3 × upper limit of normal) HBVr, which occurred in five, four and one patients, respectively, with a total HBVr rate of 1.4%. None of them had to discontinue the chemotherapy program, while two patients required a delay. Treatment-related adverse events (AEs) were reported during LAM prophylaxis in three patients (0.9%). In conclusion, this study confirms the efficacy and safety of LAM prophylaxis in anti-HBc-positive patients undergoing R-containing regimens.

Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis.

BACKGROUND & AIMS: Transient elastography (TE) is validated in chronic hepatitis C (CHC) to evaluate hepatic fibrosis; however, limited data are available in chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). This prospective study is aimed to assess the accuracy and the efficacy of TE for the detection of fibrosis in patients with chronic liver disease of different etiology and to evaluate the effect of steatosis on the liver stiffness measurement (LSM). METHODS: TE was performed in 219 consecutive patients with chronic liver disease (35% CHC, 32% CHB, and 33% NAFLD) within 6 months of the liver biopsy. RESULTS: LSM was related to the fibrosis stage in each group (CHC: p = 0.596, p < 0.001; CHB: p = 0.418, p < 0.001; NAFLD: p = 0.573, p < 0.001), but the correlation was less strong in CHB and NAFLD than in CHC patients. In CHB patients with histological cirrhosis (F4), the median stiffness value was almost two times lower than in patients with severe fibrosis (F3). In NAFLD patients with advanced fibrosis (F3) and severe steatosis (> 33%), the LSM values were lower than expected and were similar to those of patients with initial fibrosis (F1) and fat < 33%. TE underestimated the stage of fibrosis in 75% of patients with F3 and steatosis > 33%. At multiple logistic regression analysis, in CHC and CHB patients, LSM was the only predictive variable of severe fibrosis/cirrhosis (OR = 1.42, p = 0.003 and OR = 1.354, p = 0.003, respectively), while in NAFLD subjects BMI and AST (OR = 1.433, p = 0.002 and OR = 1.053, p = 0.020, respectively) but not LSM were independently related with advanced fibrosis and cirrhosis. CONCLUSIONS: This study confirms that TE can be considered a valid support to detect fibrosis in chronic liver disease related to HCV but it should be interpreted cautiously in CHB and NAFLD patients, where host or disease-related factors may modify its accuracy.

Transjugular intrahepatic portosystemic shunt in refractory ascites: clinical impact of left ventricular diastolic dysfunction.

BACKGROUND AND AIMS: Left ventricular diastolic dysfunction (LVDD) in cirrhotics are associated with circulatory dysfunction, hepatorenal syndrome (HRS) and heart failure in stressful conditions. Transjugular intrahepatic portosystemic shunt (TIPS) exacerbates the hyperdynamic circulation and challenges cardiac function. We evaluated the incidence and the impact of LVDD in cirrhotic candidates to TIPS for refractory ascites. METHODS: Among 135 patients who underwent TIPS for refractory ascites, 63 cases (child B/C 53/10, Na-model for end-stage liver disease 16.5 ± 0.9) who had 2D-transthoracic-echocardiography with tissue-Doppler-imaging pre-TIPS were retrospectively analysed (group A); in 23 cases cardiac and hormonal assessment before and after TIPS was available. 41 cirrhotics without refractory ascites treated by banding ligation for variceal re-bleeding were used as controls (group B). RESULTS: The prevalence of LVDD was higher in group A (59%; 22% with grade ≥2) as compared to group B (35%; 7% with grade ≥2) (P < 0.01 and P < 0.03). A lack of clinical response to TIPS occurred in 10 patients, all with LVDD (P < 0.03 vs. no LVDD) and in patients with grade ≥2 LVDD mostly (P < 0.02 vs. grade 1). Central venous pressure >20 mmHg after TIPS and left ventricular end-diastolic volume at basal were predictors of no response to TIPS (P = 0.01 and P = 0.004, respectively), which was an independent predictor of death. Elevated levels of NT-proBNP 3 days after TIPS were associated with advanced cardiac dysfunction (P = 0.005). CONCLUSION: NT-proBNP and careful LVDD investigation are useful to better select patients and to predict clinical response and mortality after TIPS.

Hepatitis B virus reactivation and efficacy of prophylaxis with lamivudine in patients undergoing allogeneic stem cell transplantation.

Patients previously infected with hepatitis B virus (HBV) undergoing an allograft and recipients from HBV carrier donors are at risk of posttransplant viral reactivation. The role of prophylaxis with lamivudine remains unclear. One hundred seventeen patients, with a median age of 52 years (20-67 years), with various hematologic malignancies transplanted between 1999 and 2007 entered the study. Eighty-seven recipients negative for HBV surface antigen (HBsAg), antihepatitis B core antigen antibodies (anti-HBc), and HBV-DNA with HBsAg and HBV-DNA negative donors were defined as at low risk of HBV reactivation, whereas all the remaining 30 patients were defined as at high risk. Patients at high risk transplanted in 2005 or after received lamivudine to prevent HBV reactivation as per the Italian guidelines by the Associazione Italiana per lo Studio del Fegato (AISF). Patients at low risk did not experience HBV reactivation/hepatitis. Among the recipients at high risk, 11 of 25 anti-HBc positive, those HBsAg positive (2 of 2) or negative but transplanted from HBsAg positive donors (3 of 3) were treated with lamivudine. None of these developed HBV reactivation/hepatitis after a median follow-up of 40 months (17-55 months). Hepatitis developed in 3 anti-HBc positive untreated patients conditioned with a reduced-intensity regimen. Hepatitis B was not observed in recipients at low risk, transplanted from HBsAg negative/anti-HBc positive or negative donors. Lamivudine was effective in controlling reactivation in: HBsAg positive recipients, in patients transplanted from HBsAg positive donors and in HBsAg negative/antiHBc positive recipients, who showed a significant risk of reactivation if not given prophylaxis (NCT 00876148).

Liver stiffness-based model for portal hypertension and hepatocellular cancer risk in HBV responsive to antivirals.

BACKGROUND: In hepatitis B virus (HBV)-related cirrhosis the antiviral therapy reduces portal hypertension (PH) and risk of hepatocellular carcinoma (HCC). This study assessed the prognostic role of LSPS Score (liver stiffness value X spleen diameter/platelet count) in predicting these goals in cirrhotic patients responsive to antiviral therapy. METHODS: The correlation between LSPS, PH, esophageal varices (EVs) and HCC was evaluated in 121 cirrhotic patients treated with nucleos(t)ide analogues (NUCs). Sixty-one patients (50.4%) had PH at baseline. All were HBV DNA negative on-treatment. They were evaluated after a median of 8 years of therapy (1-17) for LSPS, PH, hepatic venous pressure gradient (HVPG), EVs and HCC. RESULTS: LSPS ≤0.62 and ≤1.4 identified patients without PH measured by HVPG (<6 mmHg, NPV=100%) and EVs (PPV 63.3%, NPV 93.7%), respectively. After antiviral therapy LSPS≤0.62 was detected in 51.3% of the patients (16.4% and 76.6% of subjects with and without PH at baseline, P<0.0001). HCC developed in 26 patients (21.5%, 2.6%-year) with a higher incidence in patients with LSPS>0.62 after antiviral therapy (36% vs. 7%, P<0.001). On multivariate analysis LSPS post-therapy and PH at baseline were the only independent predictors of HCC (OR: 1.18; 95% CI: 1.02-1.28, P=0.02 and OR: 1.70; 95% CI:1-2.86, P=0.04 respectively). CONCLUSIONS: LSPS is useful to identify patients with regression of PH and EVs, avoiding endoscopy. LSPS≤0.62 at baseline or due to antiviral therapy is associated with a lower risk of HCC. Early antiviral treatment is recommended in order to maintain or to induce LSPS≤0.62.

Comparison of the Cobas Ampliprep/Cobas TaqMan HBV Test versus the Cobas Amplicor HBV monitor for HBV-DNA detection and quantification during antiviral therapy.

Performances of the new automatic system COBAS AmpliPrep/COBAS TaqMan 48 (CAP/CTM) (Roche, Branchburg, NJ) for HBV DNA extraction and real-time PCR quantification were assessed and compared with the endpoint PCR COBAS AMPLICOR HBV Monitor (CAHBM, Roche). Analytical evaluation with proficiency panels from UK National External Quality Assessment Scheme (UK NEQAS) over a 1-year period of distribution showed that CAP/CTM correctly measured HBV DNA levels with a close correlation between expected and observed values (r=0.995). Clinical evaluation as tested with samples from 11 HBsAg-positive patients undergoing antiviral therapy (71 serial specimens of plasma), demonstrated excellent correlation with CAHBM (r=0.958, mean difference in quantitation: 0.14 log, IU/ml), but CAP/CTM detected longer period of residual viremia. HBV DNA reduction was much higher in the combination schedule (Lamivudine+Adefovir), than in Adefovir monotherapy (5.1 vs. 3.5 logs). In conclusion, CAP/CTM allows for an accurate and standardized quantification of HBV DNA in high through-put laboratories. Due to it high sensitivity, it may further improve the detection of emerging drug resistance strains and the assessment of antiviral therapy.

Prevalent use of combined prophylaxis of hepatitis B after liver transplantation in Italy: results of a national survey in a large cohort.

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules. METHODS: This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers. RESULTS: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts. CONCLUSIONS: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

Microangiopathic hemolytic anemia caused by a signet-ring cell carcinoma of the intrahepatic bile duct.

Microangiopathic hemolytic anemia (MAHA) originates from a mechanical injury of red cells, caused by vascular thrombosis or stenosis. Cancer is a cause of MAHA as a consequence of both chemotherapy and disseminated disease itself. Here we describe the case of a 60-year-old man who developed a signet-ring cell carcinoma originated from the intrahepatic bile ducts, complicated by bone marrow metastasis and MAHA.

Hepatitis B in patients with hematological diseases: An update.

Hepatitis B virus (HBV) reactivation (HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories (active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugs and liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.

Consensus conference on TIPS management: Techniques, indications, contraindications.

The trans jugular intrahepatic Porto systemic shunt (TIPS) is no longer viewed as a salvage therapy or a bridge to liver transplantation and is currently indicated for a number of conditions related to portal hypertension with positive results in survival. Moreover, the availability of self-expandable polytetrafluoroethylene (PTFE)-covered endoprostheses has dramatically improved the long-term patency of TIPS. However, since the last updated International guidelines have been published (year 2009) new evidence have come, which have open the field to new indications and solved areas of uncertainty. On this basis, the Italian Association of the Study of the Liver (AISF), the Italian College of Interventional Radiology-Italian Society of Medical Radiology (ICIR-SIRM), and the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI) promoted a Consensus Conference on TIPS. Under the auspices of the three scientific societies, the consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Bergamo on June 4th and 5th, 2015. The final statements presented here were graded according to quality of evidence and strength of recommendations and were approved by an independent jury. By highlighting strengths and weaknesses of current indications to TIPS, the recommendations of AISF-ICIR-SIRM-SIAARTI may represent the starting point for further studies.