Marcello Maida | Università degli Studi di Palermo (original) (raw)

Papers by Marcello Maida

Research paper thumbnail of Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis

Analytical cellular pathology (Amsterdam), 2015

Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a de... more Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson's trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE). Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein. Results. MT, SR, and orcein staining showed concordant results in 89.6% of cases in staging CHC, without significant difference in both semiquantitative and quantitative evaluations of fibrosis. TE values were concordant with orcein levels in 86.5% of the cases and with MT/RS in 77.5% (P < 0.001). No significant correlation between the gr...

Research paper thumbnail of Refining prognosis after trans-arterial chemo-embolization for hepatocellular carcinoma

Liver International, 2015

To develop an individual prognostic calculator for patients with unresectable hepatocellular carc... more To develop an individual prognostic calculator for patients with unresectable hepatocellular carcinoma (HCC) undergoing trans-arterial chemo-embolization (TACE). Data from two prospective databases, regarding 361 patients who received TACE as first-line therapy (2000 - 2012), were reviewed in order to refine available prognostic tools and to develop a continuous individual web-based prognostic calculator. Patients with neoplastic portal vein invasion were excluded from the analysis. The model was built following a bootstrap re-sampling procedure aimed at identifying prognostic predictors and by carrying out a 10-fold cross validation for accuracy assessment by means of Harrell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s c-statistic. Number of tumours, serum albumin, serum total bilirubin, alpha-fetoprotein and maximum tumour size were selected as predictors of mortality following TACE with the bootstrap re-sampling technique. In the 10-fold cross-validation cohort, the model showed a Harrell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s c-statistic of 0.649 (95%CI: 0.610 - 0.688), significantly higher than that of the Hepatoma Arterial-embolization Prognostic (HAP) score (0.589; 95%CI: 0.552 - 0.626; P=0.001) and of the modified HAP-II score (0.611; 95%CI: 0.572 - 0.650; P=0.005). Akaike&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s information criterion for the model was 2520; for the mHAP-II it was 2544 and for the HAP score it was 2554. A web-based calculator was developed for quick consultation at http://www.livercancer.eu/mhap3.html CONCLUSIONS: The proposed individual prognostic model can provide an accurate prognostic prediction for each patient with unresectable HCC following treatment with TACE without class stratification. The availability of an online calculator can help physicians in daily clinical practice. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Second line systemic therapies for hepatocellular carcinoma: Reasons for the failure

World journal of hepatology, Jan 18, 2015

Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an inc... more Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase III trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-to-head comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for advanced hepatocellular carcinoma, failed to demonstrate an increased survival compared to placebo. What are the possible reasons for the failure? What we should expect in the near future?

Research paper thumbnail of Sorafenib for Hepatocellular Carcinoma: From Randomized Controlled Trials to Clinical Practice

Digestive Diseases, 2015

Hepatocellular carcinoma is a challenging malignancy of global importance. It is the sixth most c... more Hepatocellular carcinoma is a challenging malignancy of global importance. It is the sixth most common solid malignancy and the third leading cause of cancer-related death, worldwide. Curative treatments at early stages include liver transplantation, resection and percutaneous ablation, while transarterial chemoembolization can improve survival in patients with intermediate tumor stage. Patients with mild, related symptoms and/or macrovascular invasion or extrahepatic spread are classified under the advanced stage. The standard of care in this group is sorafenib, an inhibitor of Raf kinase and vascular endothelial growth factor receptor, whose effectiveness has been proven by 2 recent randomized controlled trials (RCTs). The aim of this brief review is to highlight the main concerns and pitfalls and to analyze the recent data of literature regarding the efficacy and the management of sorafenib therapy from RCTs to real practice.

Research paper thumbnail of Hepatitis C Virus Infection is Associated With Increased Cardiovascular Mortality: A Meta-analysis of Observational Studies

Research paper thumbnail of TM6SF2 rs58542926 is not associated with steatosis and fibrosis in large cohort of patients with genotype 1 chronic hepatitis C

Liver International, 2015

We tested the putative association of the rs58542926 variant of TM6SF2, a recently described gene... more We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5%), mild-moderate(5-29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosis severity (P = 0.63), compared to noncarriers. Prevalence and severity of steatosis were reduced in IL28B C allele carriers (P = 0.005) and elevated in PNPLA3 G allele carriers (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). After adjustment for age, gender, body mass index and homoeostasis model assessment score, steatosis severity was independently associated with IL28B rs12979860 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55-0.86, P = 0.001) and PNPLA3 rs738409 (OR 1.84, 95% CI 1.46-2.83, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but not TM6SF2 rs58542926 (OR 1.48, 95% CI 0.82-2.69, P = 0.19). Variants of TM6SF2 (30.9% vs. 25%, P = 0.40), IL28B and PNPLA3 were not directly associated with fibrosis severity, although variants of IL28B and PNPLA3 promoted steatosis (OR 1.36, 95% CI 1.06-1.75, P = 0.01) that in turn is associated with severe fibrosis. In G1 CHC patients, TM6SF2 rs58542926 does not affect the histological severity of liver damage. However, IL28B rs12979860 and PNPLA3 rs738409 modify steatosis.

Research paper thumbnail of The Severity of Steatosis Influences Liver Stiffness Measurement in Patients with Nonalcoholic Fatty Liver Disease

Research paper thumbnail of Insulin Resistance, Steatosis and Progression of Fibrosis in Patients with Genotype 1 Chronic Hepatitis C

Research paper thumbnail of P965 Personalized Therapy with Sorafenib for Hepatocellular Carcinoma

Journal of Hepatology, 2014

Research paper thumbnail of 262 Survival of Patients with Hepatocellular Carcinoma (HCC) is Affected by Complete Response to Radio-Frequency Thermal Ablation (Rfta)

Journal of Hepatology, 2013

Research paper thumbnail of 539 DRUG-INDUCED LIVER INUJRY: THE IMPACT OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

Journal of Hepatology, 2013

Research paper thumbnail of Assessment of treatment response in hepatocellular carcinoma: a review of the literature

Research paper thumbnail of Personalized sorafenib therapy for hepatocellular carcinoma

Digestive and Liver Disease, 2013

Research paper thumbnail of T-38 Survival of patients with hepatocellular carcinoma (HCC) is affected by complete response to radio-frequency thermal ablation (RFTA)

Digestive and Liver Disease, 2013

Research paper thumbnail of OC.03.4 Insulin Resistance, Steatosis and Progression of Fibrosis in Patients with Genotype 1 Chronic Hepatitis C

Digestive and Liver Disease, 2010

Research paper thumbnail of P.127 Hepatic Steatosis is Associated with Severe Fibrosis in Patients with Chronic Hepatitis B

Digestive and Liver Disease, 2010

Research paper thumbnail of T-18 Natural history of primary biliary cirrhosis: experience from a single center in southern Italy

Digestive and Liver Disease, 2012

Research paper thumbnail of P.11.1 DRUG-INDUCED LIVER INJURY: THE IMPACT OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

Digestive and Liver Disease, 2013

Research paper thumbnail of P.18.10 IL28-B Polymorphisms and Natural History of Primary Biliary Cirrhosis

Digestive and Liver Disease, 2013

Research paper thumbnail of Post sorafenib survival in patients with advanced hepatocellular carcinoma: The role of tumor progression and liver impairment

Digestive and Liver Disease, 2014

Research paper thumbnail of Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis

Analytical cellular pathology (Amsterdam), 2015

Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a de... more Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson's trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE). Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein. Results. MT, SR, and orcein staining showed concordant results in 89.6% of cases in staging CHC, without significant difference in both semiquantitative and quantitative evaluations of fibrosis. TE values were concordant with orcein levels in 86.5% of the cases and with MT/RS in 77.5% (P < 0.001). No significant correlation between the gr...

Research paper thumbnail of Refining prognosis after trans-arterial chemo-embolization for hepatocellular carcinoma

Liver International, 2015

To develop an individual prognostic calculator for patients with unresectable hepatocellular carc... more To develop an individual prognostic calculator for patients with unresectable hepatocellular carcinoma (HCC) undergoing trans-arterial chemo-embolization (TACE). Data from two prospective databases, regarding 361 patients who received TACE as first-line therapy (2000 - 2012), were reviewed in order to refine available prognostic tools and to develop a continuous individual web-based prognostic calculator. Patients with neoplastic portal vein invasion were excluded from the analysis. The model was built following a bootstrap re-sampling procedure aimed at identifying prognostic predictors and by carrying out a 10-fold cross validation for accuracy assessment by means of Harrell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s c-statistic. Number of tumours, serum albumin, serum total bilirubin, alpha-fetoprotein and maximum tumour size were selected as predictors of mortality following TACE with the bootstrap re-sampling technique. In the 10-fold cross-validation cohort, the model showed a Harrell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s c-statistic of 0.649 (95%CI: 0.610 - 0.688), significantly higher than that of the Hepatoma Arterial-embolization Prognostic (HAP) score (0.589; 95%CI: 0.552 - 0.626; P=0.001) and of the modified HAP-II score (0.611; 95%CI: 0.572 - 0.650; P=0.005). Akaike&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s information criterion for the model was 2520; for the mHAP-II it was 2544 and for the HAP score it was 2554. A web-based calculator was developed for quick consultation at http://www.livercancer.eu/mhap3.html CONCLUSIONS: The proposed individual prognostic model can provide an accurate prognostic prediction for each patient with unresectable HCC following treatment with TACE without class stratification. The availability of an online calculator can help physicians in daily clinical practice. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Second line systemic therapies for hepatocellular carcinoma: Reasons for the failure

World journal of hepatology, Jan 18, 2015

Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an inc... more Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase III trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-to-head comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for advanced hepatocellular carcinoma, failed to demonstrate an increased survival compared to placebo. What are the possible reasons for the failure? What we should expect in the near future?

Research paper thumbnail of Sorafenib for Hepatocellular Carcinoma: From Randomized Controlled Trials to Clinical Practice

Digestive Diseases, 2015

Hepatocellular carcinoma is a challenging malignancy of global importance. It is the sixth most c... more Hepatocellular carcinoma is a challenging malignancy of global importance. It is the sixth most common solid malignancy and the third leading cause of cancer-related death, worldwide. Curative treatments at early stages include liver transplantation, resection and percutaneous ablation, while transarterial chemoembolization can improve survival in patients with intermediate tumor stage. Patients with mild, related symptoms and/or macrovascular invasion or extrahepatic spread are classified under the advanced stage. The standard of care in this group is sorafenib, an inhibitor of Raf kinase and vascular endothelial growth factor receptor, whose effectiveness has been proven by 2 recent randomized controlled trials (RCTs). The aim of this brief review is to highlight the main concerns and pitfalls and to analyze the recent data of literature regarding the efficacy and the management of sorafenib therapy from RCTs to real practice.

Research paper thumbnail of Hepatitis C Virus Infection is Associated With Increased Cardiovascular Mortality: A Meta-analysis of Observational Studies

Research paper thumbnail of TM6SF2 rs58542926 is not associated with steatosis and fibrosis in large cohort of patients with genotype 1 chronic hepatitis C

Liver International, 2015

We tested the putative association of the rs58542926 variant of TM6SF2, a recently described gene... more We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5%), mild-moderate(5-29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosis severity (P = 0.63), compared to noncarriers. Prevalence and severity of steatosis were reduced in IL28B C allele carriers (P = 0.005) and elevated in PNPLA3 G allele carriers (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). After adjustment for age, gender, body mass index and homoeostasis model assessment score, steatosis severity was independently associated with IL28B rs12979860 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55-0.86, P = 0.001) and PNPLA3 rs738409 (OR 1.84, 95% CI 1.46-2.83, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), but not TM6SF2 rs58542926 (OR 1.48, 95% CI 0.82-2.69, P = 0.19). Variants of TM6SF2 (30.9% vs. 25%, P = 0.40), IL28B and PNPLA3 were not directly associated with fibrosis severity, although variants of IL28B and PNPLA3 promoted steatosis (OR 1.36, 95% CI 1.06-1.75, P = 0.01) that in turn is associated with severe fibrosis. In G1 CHC patients, TM6SF2 rs58542926 does not affect the histological severity of liver damage. However, IL28B rs12979860 and PNPLA3 rs738409 modify steatosis.

Research paper thumbnail of The Severity of Steatosis Influences Liver Stiffness Measurement in Patients with Nonalcoholic Fatty Liver Disease

Research paper thumbnail of Insulin Resistance, Steatosis and Progression of Fibrosis in Patients with Genotype 1 Chronic Hepatitis C

Research paper thumbnail of P965 Personalized Therapy with Sorafenib for Hepatocellular Carcinoma

Journal of Hepatology, 2014

Research paper thumbnail of 262 Survival of Patients with Hepatocellular Carcinoma (HCC) is Affected by Complete Response to Radio-Frequency Thermal Ablation (Rfta)

Journal of Hepatology, 2013

Research paper thumbnail of 539 DRUG-INDUCED LIVER INUJRY: THE IMPACT OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

Journal of Hepatology, 2013

Research paper thumbnail of Assessment of treatment response in hepatocellular carcinoma: a review of the literature

Research paper thumbnail of Personalized sorafenib therapy for hepatocellular carcinoma

Digestive and Liver Disease, 2013

Research paper thumbnail of T-38 Survival of patients with hepatocellular carcinoma (HCC) is affected by complete response to radio-frequency thermal ablation (RFTA)

Digestive and Liver Disease, 2013

Research paper thumbnail of OC.03.4 Insulin Resistance, Steatosis and Progression of Fibrosis in Patients with Genotype 1 Chronic Hepatitis C

Digestive and Liver Disease, 2010

Research paper thumbnail of P.127 Hepatic Steatosis is Associated with Severe Fibrosis in Patients with Chronic Hepatitis B

Digestive and Liver Disease, 2010

Research paper thumbnail of T-18 Natural history of primary biliary cirrhosis: experience from a single center in southern Italy

Digestive and Liver Disease, 2012

Research paper thumbnail of P.11.1 DRUG-INDUCED LIVER INJURY: THE IMPACT OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

Digestive and Liver Disease, 2013

Research paper thumbnail of P.18.10 IL28-B Polymorphisms and Natural History of Primary Biliary Cirrhosis

Digestive and Liver Disease, 2013

Research paper thumbnail of Post sorafenib survival in patients with advanced hepatocellular carcinoma: The role of tumor progression and liver impairment

Digestive and Liver Disease, 2014