Salvatore Madonia

Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: Survival rate and prognostic factors

BACKGROUND The role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial. AIMS To evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival. METHODS From 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model. RESULTS The cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values >2mg/dl compared to patients with values <2mg/dl (Hazard ratio 3.84; CI 95% 1.70-8.66; p-value=0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20-7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18-7.05; p-value 0.02) are correlated with a worse outcome. CONCLUSIONS TACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin <2mg/dl were identified as predictors of survival.

CA 19-9 to Rule Out Pancreatic or Biliary Cancer Among Patients with Cholestasis: An Unsuitable Test?

Carbohydrate antigen CA 19-9 was initially proposed as a serologic marker for colorectal cancer [1]. Nowadays its use is not recommended for this purpose [1] and CA 19-9 serum concentration is mostly evaluated in patients with suspected pancreatic or biliary cancer, because of its presumed higher specificity in this setting [2–5]. Unfortunately, CA 19-9 levels have also been reported in other malignancies such as gastric and ovarian cancer and in different benign conditions like cystic fibrosis, hydronephrosis, and Hashimoto thyroiditis [5–7]. Furthermore, elevated CA 19-9 serum concentration can be associated with several conditions producing reduced biliary drainage [8–10], especially in the presence of cholangitis [11]. It is generally be-

Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study.

BACKGROUND Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. AIMS To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. METHODS Prospective cohort study; prognostic analysis by the Cox proportional hazards model. RESULTS A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 C) were enrolled in the study Varices were obliterated in 139 (64%) patients in a mean of 5 (+/-2.6) sessions and recurred in 58/139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US dollars 7154 per patient during the first two years of therapy. CONCLUSIONS Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients.

Modeling cost-effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real-life cohort

We evaluated the cost‐effectiveness of two alternative direct‐acting antiviral (DAA) treatment policies in a real‐life cohort of hepatitis C virus–infected patients: policy 1, “universal,” treat all patients, regardless of fibrosis stage; policy 2, treat only “prioritized” patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus–infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies’ cost‐effectiveness. The patients’ age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality‐adjusted life‐years (QALY) and incremental cost‐effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country‐specific health states costs and mean treatment cost of €30,000. For the Italian base‐case analysis, the cost‐effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost‐effective in 94%‐97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0‐F3 post–sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost‐saving for the base price (€15,000) discounts of at least 75% applied in patients with F0‐F2 fibrosis.

Marked impact of IL28B genotype in the natural clearance of hepatitis C virus in patients with haemoglobinopathies

Driss, F., Tertian, G., Becquemont, L., Haddad, B., Cynober, T., Raphael, M. & Tchernia, G. (2007) Management of high risk pregnancy in sickle cell disease by a strategy of prophylactic red cell transfusion or automated red cell exchange. Transfusion Clinique et Biologique, 14, 386–392. Kalff, A., Dowsing, C. & Grigg, A. (2010) The impact of a regular erythrocytapheresis programme on the acute and chronic complications of sickle cell disease in adults. British Journal of Haematology, 149, 768–774.

Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon‐free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct‐acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow‐up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV.

Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?

BACKGROUND Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients. AIMS We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection. METHODS We analyzed 230 TM patients with HCV infection (mean age 36.0±6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers. RESULTS By multivariate regression analysis SVR was independently associated with CC allele of IL28B SNP (OR 2.98; CI 95% 1.29-6.86; p=0.010) and rapid virologic response (OR 11.82; CI 95% 3.83-36.54; p<0.001) in 136 genotype 1 patients. Combining favorable variables the probability of SVR ranged from 31% to 93%. In genotype 2 patients, only RVR (OR 8.61; CI 95% 2.85-26.01; p<0.001) was associated with SVR higher than 80%. In 3 patients with cirrhosis a decompensation of liver or heart disease were observed. Over 50% of patients increased blood transfusions. CONCLUSION Dual therapy in TM patients with chronic HCV infection is efficacious in patients with the best virological, genetic and clinical predictors. Patients with cirrhosis have an increased risk of worsening liver or heart disease.

Does glatiramer acetate provoke hepatitis in multiple sclerosis

An association between multiple sclerosis and autoimmune hepatitis has been described. The latter can also be unmasked or exacerbated by a variety of therapies used in multiple sclerosis, such as beta-Interferon or glatiramer acetate. Two cases of hepatitis occurring after exposure to glatiramer acetate are described here: the first, was possibly due to autoimmune hepatitis, rather than glatiramer acetate induced liver injury, the second was definite autoimmune hepatitis. Both occurred in patients who had already experienced hepatitis exacerbations during previous beta-Interferon treatment. We suggest that glatiramer acetate can unmask hepatitis. Thus, liver enzyme monitoring should be undertaken frequently in those patients with multiple sclerosis receiving glatiramer acetate, with a history of hepatitis during treatment with Interferon beta-1a.

An open-safety study of dual antiviral therapy in real-world patients with chronic hepatitis C

Treatment of patients with chronic hepatitis C with alpha‐interferon and ribavirin usually produces adverse events within the first 3 months. We aimed to assess safety and predictors of discontinuation or dose modification of these drugs.

Forecasting Hepatitis C liver disease burden on real life data. Does the hidden iceberg matter to reach the elimination goals

Advances in direct‐acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked‐to‐care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030.