Publications by authors named "Antonio De Vincentis"

38 Publications

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

JHEP Rep 2021 Apr 27;3(2):100248. Epub 2021 Jan 27.

Internal Medicine and Hepatology, University Campus Bio-Medico of Rome, Rome, Italy.

Background & Aims: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions.

Methods: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to ; the secondary endpoint was the biochemical response according to , defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed.

Results: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to , and 11% by . Patients with cirrhosis had lower response than patients without cirrhosis (29.5% 49.2%,  = 0.01), owing to a higher rate of OCA discontinuation (30% 12%,  = 0.004), although with similar ALP reduction (29.4% 34%,  = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% 42.3%,  = 0.68), with higher ALT reduction at 6 months (-38% -29%,  = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%).

Conclusions: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC.

Lay Summary: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
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http://dx.doi.org/10.1016/j.jhepr.2021.100248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930359PMC
April 2021

Association between clinical scores of liver fibrosis and adverse non-hepatic outcomes: The key in the holistic vision of the patient.

J Diabetes Complications 2021 Feb 18:107891. Epub 2021 Feb 18.

Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, University Campus Bio-Medico of Rome, Rome, Italy.

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http://dx.doi.org/10.1016/j.jdiacomp.2021.107891DOI Listing
February 2021

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: analysis of the REPOSI registry.

Age Ageing 2021 02;50(2):498-504

Unit of Geriatrics, University Campus Bio-Medico, Rome, Italy.

Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce.

Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties.

Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed.

Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT.

Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.
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http://dx.doi.org/10.1093/ageing/afaa150DOI Listing
February 2021

The PNPLA3 rs738409 variant can increase the risk of liver toxicity in multiple sclerosis patients treated with beta-interferon.

Clin Neurol Neurosurg 2020 Oct 20;197:106166. Epub 2020 Aug 20.

Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico di Roma, Rome, Italy.

Background: Liver toxicity can limit the use of interferon-beta (IFNβ), a well-established treatment for multiple sclerosis (MS). Unfortunately, known risk-factors for IFNβ-associated liver toxicity are few and of limited clinical utility. Susceptibility to drug-induced toxicity is influenced by genetic factors affecting hepatic lipid metabolism and drug-metabolizing activity.

Methods: We designed a retrospective, multicentre study to evaluate whether specific polymorphisms in genes involved in hepatic lipid metabolism are associated with a higher risk of developing IFNβ-induced hepatotoxicity. The following single nucleotide polymorphisms were examined: rs738409 C > G in PNPLA3; rs4880 C > T in SOD2; rs3750861 C > T in KLF6; rs13412852 C > T in LPIN1; rs58542926 C > T in TM6SF2. Liver toxicity was defined as a new increase of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) plasma levels above the laboratory upper normal limit after the start of IFNβ treatment.

Results: One-hundred-thirteen MS patients were enrolled and twenty-nine experienced liver toxicity. Logistic regression analysis revealed that the PNPLA3 variant was significantly associated with the occurrence of liver toxicity. No associations were found between other polymorphisms and liver toxicity.

Conclusions: The results of our exploratory study suggest that the PNPLA3 variant can help to identify those patients at higher risk of IFNβ toxicity. The stratification of the risk of liver toxicity could increase the safety of IFNβ therapy.
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http://dx.doi.org/10.1016/j.clineuro.2020.106166DOI Listing
October 2020

Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis.

Mol Metab 2020 Jul 13:101049. Epub 2020 Jul 13.

Halal Research Center of IRI, FDA, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland. Electronic address:

Objective: The prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH) is increasing. NAFLD/NASH may progress to cirrhosis and hepatocellular carcinoma. However, most patients with NAFLD/NASH will die from a vascular cause. There are no approved pharmacological treatments for NASH/NAFLD. Many clinical trials have been, or are being, undertaken; however, the challenge is the assessment of the clinical endpoint. The main objective of this narrative review was to evaluate the efficacy of drugs used in clinical trials for the treatment of NAFLD/NASH that included a liver biopsy as the gold standard.

Methods: A literature search was conducted using 3 databases (PubMed, Scopus, and Google Scholar) to identify the clinical trials that included liver biopsy assessment before and after treatment.

Results: Interventional clinical trials (n = 33) involving 18 different agents, alone and in combination, were identified. Pioglitazone is the only agent that has shown consistent benefit and efficacy in clinical trials. Pentoxifylline, rosiglitazone, and ursodeoxycholic acid had both positive and negative results from clinical trials. There is also evidence for vitamin E and metformin. Other drugs, including bicyclol, cysteamine bitartrate, l-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins, each had a single clinical study.

Conclusions: In summary, the available molecules demonstrated a significant improvement in NASH and/or liver fibrosis in a minority of patients; thus, other drugs should be identified, possibly those acting on alternative pathophysiological pathways, and tested for their safety and efficacy.
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http://dx.doi.org/10.1016/j.molmet.2020.101049DOI Listing
July 2020

Return to Sport Activity in the Elderly Patients after Unicompartmental Knee Arthroplasty: A Systematic Review and Meta-Analysis.

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Deaprtment of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via A. Del Portillo, 21, 00128 Rome, Italy.

In patients with knee osteoarthritis, when only medial or lateral compartment of the knee is involved, unicompartimental knee arthroplasty (UKA) is a reliable option for addressing the symptoms and restore function. The main aim of the present review is to systematically collect the available evidence concerning the return to sport activity in the elderly patients after UKA. An electronic search was carried out on the following databases; Pubmed-Medline, Cochrane central, and Scopus, searching for randomized controlled trials, prospective cohort studies, retrospective case-control studies, and case series. Data concerning the evaluation of the return to sport (RTS) and of functional outcomes in the elderly patients after UKA surgery. MINORS score was used to assess the risk of methodological biases. Odds ratios and raw proportions were used to report the pooled effect of UKA on the return to sport in comparative and non-comparative studies, respectively. Same level RTS in elderly patients was of 86% (pooled return proportion 0.86, 95%CI 0.78, 0.94), showing also better relative RTS and time to RTS of patients undergoing UKA, in comparison to those undergoing TKA. Sport-specific RTS showed that higher return rates were observed for low-impact sports, whereas high-impact sports prevented a full return to activities. UKA is a valid and reliable option for elderly patients to satisfactorily resume their sport practice, especially for low impact activities. The rate of return to sports following UKA is higher than TKA.
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http://dx.doi.org/10.3390/jcm9061756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356230PMC
June 2020

Genetic variants in the MTHFR are not associated with fatty liver disease.

Liver Int 2020 08 11;40(8):1934-1940. Epub 2020 Jun 11.

Department of Internal Medicine and Geriatrics, University Campus Bio-Medico of Rome, Rome, Italy.

The common missense sequence variants of methylenetetrahydrofolate reductase (MTHFR), rs1801131 (c.A1298C) and rs1801133 (c.C677T), favour the development of hyperhomocysteinemia and diminished DNA methylation. Previous studies, carried out in small series and with suboptimal characterization of the hepatic phenotype, tested the association of these genetic variants with fatty liver disease (FLD), with conflicting results. Here, we assessed the association of rs1801131 and rs1801133 with hepatic phenotype in the Liver Biopsy Cross-Sectional Cohort, a large cohort (n=1375 from Italy and 411 from Finland) of European individuals with suspect FLD associated with dysmetabolism. A total of 1786 subjects were analysed by ordinal regression analyses. The rs1801131 and the rs1801133 variants were not associated with steatosis, inflammation, ballooning or fibrosis. The present study suggests that changes in folate and methionine metabolism resulting from these 2 variants are not associated with a clinically significant impact on FLD in Europeans.
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http://dx.doi.org/10.1111/liv.14543DOI Listing
August 2020

Return to Sport after Anatomic and Reverse Total Shoulder Arthroplasty in Elderly Patients: A Systematic Review and Meta-Analysis.

J Clin Med 2020 May 22;9(5). Epub 2020 May 22.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

The aim of this systematic review and meta-analysis was to evaluate the rate of return to sport in elderly patients who underwent anatomic (ATSA) and reverse (RTSA) total shoulder arthroplasty, to assess postoperative pain and functional outcomes and to give an overview of postoperative rehabilitation protocols. A systematic search in Pubmed-Medline, Cochrane Library, and Google Scholar was carried out to identify eligible randomized clinical trials, observational studies, or case series that evaluated the rate of return to sport after RTSA or ATSA. Six retrospective studies, five case series, and one prospective cohort study were included in this review. The overall rate of return to sport was 82% (95% CI 0.76-0.88, < 0.01). Patients undergoing ATSA returned at a higher rate (90%) (95% CI 0.80-0.99, < 0.01) compared to RTSA (77%) (95% CI 0.69-0.85, < 0.01). Moreover, the results showed that patients returned to sport at the same or a higher level in 75% of cases. Swimming had the highest rate of return (84%), followed by fitness (77%), golf (77%), and tennis (69%). Thus, RTSA and ATSA are effective to guarantee a significative rate of return to sport in elderly patients. A slightly higher rate was found for the anatomic implant.
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http://dx.doi.org/10.3390/jcm9051576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291255PMC
May 2020

Potentially Inappropriate Medications, Drug-Drug Interactions, and Anticholinergic Burden in Elderly Hospitalized Patients: Does an Association Exist with Post-Discharge Health Outcomes?

Drugs Aging 2020 08;37(8):585-593

Unit of Geriatrics, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 200, 00128, Rome, Italy.

Background: Polypharmacy is very common in elderly patients and is associated with detrimental outcomes.

Objective: Our objective was to evaluate the associations between a large panel of therapy quality indicators, including explicit lists of potentially inappropriate medications (PIMs; Beers criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions [STOPP] criteria), the Anticholinergic Cognitive Burden (ACB) score, and the number of drug-drug interactions (DDIs), with respect to mortality, rehospitalization, and physical function decline within 3 months from hospital discharge in a cohort of hospitalized elderly patients.

Methods: We studied 2631 individuals aged ≥ 65 years (median age 79.6; males 48.6%) enrolled in the REPOSI registry. The relationships with mortality and rehospitalization were evaluated using Cox regressions, and relationships with functional status change (as percentage variation of Barthel Index [BI]) were evaluated using mixed linear models.

Results: None of the studied indicators was associated with mortality and rehospitalization. Conversely, only ACB was associated with physical function decline, even after correction for confounders (adjusted mean BI variation of - 7.55%; 95% confidence interval [CI] - 12.37 to - 2.47). The number of medications at discharge, particularly polypharmacy (more than five drugs daily), were the only therapy-related factors associated with mortality (adjusted hazard ratio [aHR] 1.05 [95% CI 1.01-1.10] and 1.70 [95% CI 1.12-2.58], respectively) and rehospitalization (aHR 1.05 [95% CI 1.01-1.08] and 1.31 [95% CI 1.01-1.71], respectively).

Conclusion: Polypharmacy, a very simple measure, outperformed sophisticated PIM and DDI indicators of quality of therapy as a correlate of primary clinical outcomes, whereas ACB was associated with physical function decline. Thus, innovative approaches to the definition and research of PIMs and DDIs are eagerly awaited from the perspective of averaging the quantitative burden and qualitative interaction of drugs.
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http://dx.doi.org/10.1007/s40266-020-00767-wDOI Listing
August 2020

Long noncoding RNAs in nonalcoholic fatty liver disease and liver fibrosis: state-of-the-art and perspectives in diagnosis and treatment.

Drug Discov Today 2020 07 19;25(7):1277-1286. Epub 2020 May 19.

Halal Research Center of IRI, FDA, Tehran, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) significantly impacts global health. Despite considerable research, its pathophysiology remains partially unclear. In addition, selective serum biomarkers of disease diagnosis and progression are missing. Long noncoding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with crucial roles in biological processes underlying the pathophysiology of different human diseases. Recent studies have shown that lncRNA could be associated with the genesis and progression of NAFLD towards the most severe forms. Although the field is still in its infancy, it is tempting to speculate that these transcripts could be used as both diagnostic and therapeutic targets. In this review, we summarize recent findings on lncRNAs in the complex research field of NAFLD.
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http://dx.doi.org/10.1016/j.drudis.2020.05.009DOI Listing
July 2020

Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: A proof of concept study.

PLoS One 2020 21;15(5):e0233350. Epub 2020 May 21.

Geriatric Unit, Università Campus Bio-Medico, Roma, Lazio, Italy.

Background: Serum-ascites albumin gradient (SAAG) remains the most sensitive and specific marker for the differentiation of ascites due to portal hypertension from ascites due to other causes. SAAG has some limitations and may fail in selected conditions. Voltammetric analysis (VA) has been used for the detection of electroactive species of biological significance and has proven effective for detection infections in biological fluids.

Aims: In this study, we compared the accuracy of voltammetric analysis (VA) with that of SAAG to differentiate ascites due to portal hypertension from that having a different origin.

Methods: 80 ascites samples were obtained from patients undergoing paracentesis at the Campus Bio-Medico Hospital of Rome. VA was performed using the BIONOTE device. The ability of VA to discriminate ascitic fluid etiology and biochemical parameters was evaluated using Partial Least Square Discriminant Analysis (PLS-DA), with ten-fold cross-validations.

Results: Mean age was 68.6 years (SD 12.5), 58% were male. Ascites was secondary to only portal hypertension in 72.5% of cases (58 subjects) and it was secondary to a baseline neoplastic disease in 27.5% of cases (22 subjects). Compared to SAAG≥1.1, e-tongue predicted ascites from portal hypertension with a better accuracy (92.5% Vs 87.5%); sensitivity (98.3% Vs 94.8%); specificity (77.3% Vs 68.2%); predictive values (PPV 91.9% Vs 88.7% and NPV 94.4% Vs 83.3%). VA correctly classified ascites etiology in 57/58 (98.2%) of cases with portal hypertension and in 17/22 (77.2%) of cases with malignancy. Instead, VA showed poor predictive capacities towards total white blood count and polymorphonuclear cell count.

Conclusions: According to this proof of concept study, VA qualifies as a promising low-cost and easy method to discriminate between ascites secondary to portal hypertension and ascites due to malignancy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233350PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241828PMC
August 2020

Management of hip fracture in the older people: rationale and design of the Italian consensus on the orthogeriatric co-management.

Aging Clin Exp Res 2020 Jul 1;32(7):1393-1399. Epub 2020 May 1.

Geriatric and Gerontology Department, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128, Rome, Italy.

Background: Hip fracture (HF) is a burdening health problem in older people. The orthogeriatric approach has been shown to favour functional recovery and reduce mortality, but its implementation in clinical practice cannot rely upon shared management protocols and greatly varies among different healthcare systems. Here, we present the rationale and design of the Italian consensus document on the management of HF in older people.

Methods: A panel of multidisciplinary experts from ten Italian scientific societies involved in the care of HF and including geriatricians, orthopaedics, anaesthesiologists, physiatrists and general practitioners, will join to establish the content validity of a list of statements. A Delphi consensus methodology will be applied to obtain the opinions of the panel and to provide the final recommendations.

Objectives: The document will include indications on the following relevant topics: (1) optimal care path of older subjects with HF; (2) management of comorbidities and pre-operative alteration of physiological parameters; (3) management of selected categories of patients at expected increased risk of adverse outcomes; (4) continuity of care out of hospital; (5) screening and correction of risk factors for HF in older subjects; (6) information and divulgation of shared management strategies. The objective of the consensus will be to inform clinicians, patients, researchers, and health policy makers about the best management strategies for HF in older people and their inherent limitations, thus facilitating communication between stakeholders and promoting the most cost/effective models of care.
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http://dx.doi.org/10.1007/s40520-020-01574-4DOI Listing
July 2020

Impact of Low Muscle Mass and Low Muscle Strength According to EWGSOP2 and EWGSOP1 in Community-Dwelling Older People.

J Gerontol A Biol Sci Med Sci 2020 06;75(7):1324-1330

Geriatric Unit, Campus Bio-Medico University, Rome, Italy.

Background: A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people.

Methods: Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m).

Results: We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio [HR] for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval [CI] 1.04-6.94; LMS: HR 3.18, 95% CI 1.44-7.01; LMM/LMS: HR 2.95, 95% CI 0.86-10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85-10.57). None of the sarcopenia components conferred a higher risk of mobility disability.

Conclusions: The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation.
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http://dx.doi.org/10.1093/gerona/glaa063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302167PMC
June 2020

Diagnostic value of Virtual Touch Quantification (VTQ®) for differentiation of hemangiomas from malignant focal liver lesions.

Med Ultrason 2019 Nov;21(4):371-376

Hepatology and Clinical Medicine Unit of University Campus Bio Medico of Rome.

Aim: To evaluate the diagnostic value of Virtual Touch Quantification (VTQ®) for characterizing benign vs. malignant focal liver lesions (FLLs).

Material And Methods: From January 2015 to January 2016 all consecutive FLLs visualized during a conventional abdominal ultrasound (US), underwent VTQ® evaluation, taking five measurements of both the lesion and the surrounding parenchyma.

Results: We studied 119 FLLs, consisting of 52 hemangiomas (HEs), 39 hepatocellular carcinomas (HCCs), and 28 liver metastases (METs). HEs showed a significantly lower shear wave velocity (SWV) values compared to malignant FLLs (HEs SWV median value 1.34 m/sec, IQR 0.9; malignant lesions SWV median value 2.69 m/sec, IQR 1.6; p<0.001). Moreover, a nodule-to-parenchyma SWV ratio showed a significant difference in HEs and METs (p<0.001) but not in HCCs (p=0.03). SWV values were able to correctly differentiate malignant lesions with c-statistics of 0.82 (95 % CI 0.74- 0.90) and sensitivity of 74.6%/specificity of 80.7% at a cut-off of 2 m/sec.

Conclusions: Our results suggest that VTQ® is able to distinguish HEs from malignant lesions (HCCs and METs) at a SWV cut-off of 2 m/sec.
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http://dx.doi.org/10.11152/mu-2062DOI Listing
November 2019

Rate of non-response to ursodeoxycholic acid in a large real-world cohort of primary biliary cholangitis patients in Italy.

Scand J Gastroenterol 2019 Oct 28;54(10):1274-1282. Epub 2019 Sep 28.

Department of Infectious Diseases, D. Cotugno Hospital, Napoli, Italy.

Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking. Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided. Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts. A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.
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http://dx.doi.org/10.1080/00365521.2019.1669702DOI Listing
October 2019

Neurotrophic keratopathy: Pros and cons of current treatments.

Ocul Surf 2019 10 14;17(4):619-623. Epub 2019 Sep 14.

Ophthalmology Complex Operative Unit, University Campus Bio-Medico, Rome, Italy. Electronic address:

Background: Several therapeutics have been proposed for neurotrophic keratitis, but no direct comparison among different approaches is available.

Objective: To compare treatment-related problems and outcomes of both traditional and novel therapeutics for neurotrophic keratopathy, focusing on resolution rate, healing time, and recurrence rate.

Data Sources: Literature search of published studies between 1980 and 2019 on neurotrophic keratopathy available on PubMed was made without any language constraints but limited to human study participants.

Study Selection: All published peer-reviewed open, blinded and randomized clinical trials, case series and case reports, divided according to evidence level, were reviewed and resolution rate, healing time, relapses of the disease, and visual outcomes were evaluated.

Data Extraction And Synthesis: Single observer data extraction. MAIN OUTCOMES AND MEASURES: resolution rate, healing time, recurrence rate.

Results: Human recombinant Nerve Growth Factor eye drops, Serum Tears and Substance P showed comparable resolution rate in patients with neurotrophic keratopathy. Amniotic membrane transplantation and Nerve Growth Factor eye drops are associated with a faster healing time among available treatments. Nerve Growth Factor eye drops clinical trial are the only study with evidence level 1, hence randomized and controlled.

Conclusions And Relevance: Several new treatment options are available for patients with neurotrophic keratitis with adequate safety.
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http://dx.doi.org/10.1016/j.jtos.2019.09.002DOI Listing
October 2019

Exhaled breath analysis in hepatology: State-of-the-art and perspectives.

World J Gastroenterol 2019 Aug;25(30):4043-4050

Unit of Clinical Medicine and Hepatology, Unit of Geriatrics, Department of Medicine, Campus Bio-Medico University Hospital, Rome 00128, Italy.

Liver disease is characterized by breath exhalation of peculiar volatile organic compounds (VOCs). Thanks to the availability of sensitive technologies for breath analysis, this empiric approach has recently gained increasing attention in the context of hepatology, following the good results obtained in other fields of medicine. After the first studies that led to the identification of selected VOCs for pathophysiological purposes, subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application. Specific VOC patterns were found to discriminate subjects with liver cirrhosis, to rate disease severity, and, eventually, to forecast adverse clinical outcomes even beyond existing scores. Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease. However, clinical translation is still hampered by a number of methodological limitations, including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results. Given the low-cost and easy execution at bedside of the new technologies (e-nose), larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.
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http://dx.doi.org/10.3748/wjg.v25.i30.4043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700691PMC
August 2019

Drug-drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients.

Eur J Intern Med 2019 Jul 10;65:51-57. Epub 2019 May 10.

Unit of Internal Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy; Unit of Geriatrics, University Campus Bio-Medico, Rome, Italy.

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Società Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0-9.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients.
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http://dx.doi.org/10.1016/j.ejim.2019.05.002DOI Listing
July 2019

Association between non-invasive liver fibrosis scores and occurrence of health adverse outcomes in older people.

Dig Liver Dis 2019 09 3;51(9):1330-1336. Epub 2019 Feb 3.

Geriatric and Gerontology Department, Campus Bio-Medico University, Rome, Italy.

Background: The relation between liver fibrosis scores and health outcomes in older people has been barely investigated. We aimed to evaluate the association of four liver fibrosis scores (fibrosis-4 -FIB-4-, NAFLD fibrosis score -NFS-, BARD and aspartate aminotransferase/alanine aminotransferase ratio -AST/ALT-) with mortality and incident disability at 6 years in an older population.

Methods: We studied 962 individuals aged ≥65 (mean age 74.4; female 55.5%) with a mean follow-up of 95.7 months, enrolled in the InCHIANTI study. The relationship between liver fibrosis scores and mortality and disability was assessed through Cox and log-binomial regressions.

Results: NFS and FIB-4 were associated with higher overall (aHR ranging 1.38-1.78 for intermediate risk of fibrosis and 1.60-2.02 for high risk) and cardiovascular (aHR ranging 1.76-2.90 for intermediate and 2.22-2.42 for high risk) mortality. AST/ALT and BARD were only associated with overall mortality. Only NFS and FIB-4 high risk classes were associated with incident disability (aRR ranging 1.93-2.76). Despite poor sensitivity, all scores showed high specificity (ranging 0.88-0.95).

Conclusion: Higher risk of liver fibrosis is associated with higher risk of poor health outcomes. Liver fibrosis scores may help to stratify the risk and, mainly, identify elderly patients with favorable prognosis.
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http://dx.doi.org/10.1016/j.dld.2019.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679815PMC
September 2019

Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study.

Can J Gastroenterol Hepatol 2018 14;2018:7564835. Epub 2018 Mar 14.

Internal Medicine, Geriatrics, and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Background & Aims: Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis.

Methods: Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped.

Results: One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants ( < 0.001, < 0.05, and = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis.

Conclusions: The effects determined by disease-associated variants at different can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.
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http://dx.doi.org/10.1155/2018/7564835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872672PMC
March 2019

Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients.

Eur J Intern Med 2018 08 9;54:60-64. Epub 2018 Apr 9.

Department of Medicine, University Campus Bio-Medico, Rome, Italy.

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from "Registro Politerapia Società Italiana di Medicina Interna (REPOSI)". Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60-0.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients.
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http://dx.doi.org/10.1016/j.ejim.2018.04.001DOI Listing
August 2018

Screening of Obstructive Sleep Apnea Syndrome by Electronic-Nose Analysis of Volatile Organic Compounds.

Sci Rep 2017 09 20;7(1):11938. Epub 2017 Sep 20.

Geriatrics, Department of Respiratory Pathophysiology, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.

Obstructive Sleep Apnea Syndrome (OSAS) carries important social and economic implications. Once the suspicion of OSAS has arisen, Polysomnography (PSG) represents the diagnostic gold standard. However, about 45% of people who have undergone PSG are free from OSAS. Thus, efforts should be made to improve the selection of subjects. We verified whether the pattern of Volatile Organic Compounds (VOCs) helps to select patients amenable to PSG. We studied 136 subjects (20 obese non-OSAS, 20 hypoxic OSAS, 20 non-hypoxic OSAS, and 20 non-hypoxic Chronic Obstructive Pulmonary Disease (COPD) vs 56 healthy controls) without any criteria of exclusion for comorbidity to deal with a real-life population. VOCs patterns were analyzed using electronic-nose (e-nose) technology. A Discriminant Analysis (Partial Least Square-Discriminant Analysis) was performed to predict respiratory functions and PSG parameters. E-nose distinguished controls (100% correct classification) from others and identified 60% of hypoxic, and 35% of non-hypoxic OSAS patients. Similarly, it identified 60% of COPD patients. One-by-one group comparison yielded optimal discrimination of OSAS vs controls and of COPD vs controls (100% correct classification). In conclusion, e-nose technology applied to breath-analysis can discriminate non-respiratory from respiratory diseased populations in real-life multimorbid populations and exclude OSAS. If confirmed, this evidence may become pivotal for screening purposes.
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http://dx.doi.org/10.1038/s41598-017-12108-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607284PMC
September 2017

Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival.

J Gerontol A Biol Sci Med Sci 2018 06;73(7):925-930

Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy.

Background: Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, the determinants subtending this association have been poorly explored. To gain insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia, and pyridoxine levels were systematically assessed.

Methods: Data are from 765 participants aged more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates.

Results: ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio [HR] 0.98 [0.96-1], p = .02; cardiovascular: 0.94 [0.9-0.98], p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality.

Conclusions: These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored.
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http://dx.doi.org/10.1093/gerona/glx126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001897PMC
June 2018

Platelet count may impact on lysosomal acid lipase activity determination in dried blood spot.

Clin Biochem 2017 Aug 24;50(12):726-728. Epub 2017 Feb 24.

Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Background: We aimed to evaluate the influence of white blood cell (WBC) and platelet (PLT) counts on dried blood spot (DBS)-determined lysosomal acid lipase (LAL) activity in a large group of healthy subjects.

Methods: One-hundred-and-seventy-two healthy subjects aged ≥18 were enrolled. Complete clinical biochemistry and LAL activity in DBS were determined. In 35 subjects, WBCs and PLTs were isolated, and LAL activity was measured in both blood cell populations. Univariate and multivariate analyses to DBS-LAL activity were performed.

Results: Mean age of subjects was 44.8±17.2years, 43.6% were males, and mean DBS-LAL activity was normal (1.0±0.3nmol/spot/h). LAL activity in WBCs was significantly higher than in PLTs (458.9±133.6 vs 235.0±88.3nmol/mg/h, p<0.001). However, LAL activity in DBS correlated more strongly with that in PLTs (r=0.65, p<0.001) than with that in WBCs (r=0.49, p<0.01). Consistently, in the multivariate model, DBS-LAL activity was independently associated only with PLT count (β=0.39, p<0.001).

Conclusions: PLT number may impact on the result of the DBS-LAL test, and a consideration of PLT count is recommended before interpreting LAL activity in DBS.
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http://dx.doi.org/10.1016/j.clinbiochem.2017.02.013DOI Listing
August 2017

Effect of Sibutramine on Plasma C-Reactive Protein, Leptin and Adipon ectin Concentrations: A Systematic Review and Meta-Analysis of Randomized Contr olled Trials.

Curr Pharm Des 2017 ;23(6):870-878

Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Sibutramine is an anti-obesity medication whose effects on weight loss have been widely explored. Moreover, limited number of studies also evidenced its correlates on adipokines and proinflammatory markers; however, their results have not been conclusive. Hence, a systematic review and meta-analysis of available evidence was conducted in order to calculate the effect size of sibutramine therapy on C-reactive protein (CRP), leptin and adiponectin concentrations. Seven randomized clinical trials with a total of 601 subjects met the eligibility criteria. Random effect meta-analysis evidenced a significant decrease in plasma levels of CRP and leptin (weighted mean difference [WMD] -15.58%, 95% confidence interval [95%CI]: -28.84, -2.33, p=0.021 and WMD -9.25, 95%CI: -15.73, -2.78, p=0.005, respectively) and increase of adiponectin (WMD 9.86%, 95%CI: 1.76, 17.96, p=0.017) following sibutramine therapy. Subgroup analysis showed a greater CRP-lowering effect of sibutramine with doses <15 mg/day (WMD -17.26%, 95%CI: -31.02, -3.5, p=0.014) compared with doses .15 mg/day (WMD 6.01%, 95%CI: -43.38, 55.40, p=0.811). In meta-regression analysis, changes in CRP were found to be independent of baseline or percentage change in body mass index. These results suggest a significant improvement of plasma CRP, leptin and adiponectin levels following treatment with sibutramine. Possible impacts and relevance of these alterations on cardiovascular risk profile remain to be clarified, especially in post-hoc analyses of sibutramine outcome trials among people without pre-existing cardiovascular disease.
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http://dx.doi.org/10.2174/1381612822666161006122934DOI Listing
February 2018

Breath-print analysis by e-nose may refine risk stratification for adverse outcomes in cirrhotic patients.

Liver Int 2017 02 21;37(2):242-250. Epub 2016 Aug 21.

Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy.

Background & Aims: The spectrum of volatile organic compounds in the exhaled breath (breath-print, BP) has been shown to characterize patients with cirrhosis and with worse hepatic function. However, the association of different BPs with clinically relevant outcomes has not been described yet. Hence, we aimed to evaluate the association between BPs, mortality and hospitalization in cirrhotic patients and to compare it with that of the "classical" prognostic indices (Child-Pugh Classification [CPC] and MELD).

Methods: Eighty-nine cirrhotic patients (M/F 59/30, mean age 64.8 ± 11.3, CPC A/B/C 37/33/19) were recruited and followed up for a median time of 23 months. Clinical and biochemical data were collected. Breath collection and analysis were obtained through Pneumopipe and BIONOTE e-nose respectively.

Results: Four different BP clusters (A, B, C, D) were identified. BP clusters A and D were associated with a significantly increased risk of mortality (HR 2.9, 95% confidence intervals [CI] 1.5-5.6) and hospitalization (HR 2.6, 95% CI 1.4-4.6), even in multiple adjusted models including CPC and MELD score (adjusted [a]HR 2.8, 95% CI 1.1-7.0 for mortality and aHR 2.2, 95% CI 1.1-4.2 for hospitalization). CPC C maintained the strongest association with both mortality (aHR 17.6, 95% CI 1.8-174.0) and hospitalization (aHR 12.4, 95% CI 2.0-75.8).

Conclusions: This pilot study demonstrates that BP clusters are associated with significant clinical endpoints (mortality and hospitalization) even independently from "classical" prognostic indices. Even though further studies are warranted on this topic, our findings suggest that the e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in cirrhotic patients.
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http://dx.doi.org/10.1111/liv.13214DOI Listing
February 2017

Hepatocellular Carcinoma in Alcoholic Liver Disease: Current Management and Recent Advances.

Rev Recent Clin Trials 2016 ;11(3):238-252

Internal Medicine and Hepatology Unit, Campus Bio Medico University of Rome, Italy.

Hepatocellular Carcinoma (HCC) is a major healthcare problem. Almost ninety percent of HCCs develops on cirrhosis due to chronic viral hepatitis, Non-Alcoholic Steatohepatitis (NASH) and alcohol abuse. Alcohol itself is defined a strong human carcinogenic agent. Some genetic polymorphisms in alcohol-metabolizing systems and more recently, some sequence variations within the genes coding for patatin-like phospholipase encoding 3 (PNPLA3) and Transmembrane 6 superfamily 2 (TM6SF2), have been found to promote liver fibrosis in alcohol abuse, until HCC development. The current management of HCC is related to tumor burden and liver function and it does not differ in alcoholics, although in alcoholics the surveillance for HCC could be less effective because socioeconomic context, such as the recall policy, the stage at the diagnosis and the prognosis are not different compared to viral HCCs. On regards of loco-regional treatment options, there have not been significant advances in the last few years, though an increasing role will be probably reserved to radio embolization and irreversible electroporation in the next future. Sorafenib (SOR) is still the only drug approved as systemic therapy in patients with HCC, whereas immunotherapy represents a promising approach for the treatment of HCC.
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http://dx.doi.org/10.2174/1574887111999160701091605DOI Listing
January 2018

Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known Etiology.

PLoS One 2016 24;11(5):e0156113. Epub 2016 May 24.

Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy.

Conclusion: Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precise causes and consequences of which need to be further addressed. DBS-determined lysosomal enzyme activities seem to be affected by white blood cell and platelet counts, and the specificity of these tests can be reduced when applied to determined populations, such as cirrhotics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156113PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878774PMC
July 2017

The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients.

Scand J Gastroenterol 2016 Aug 6;51(8):967-73. Epub 2016 May 6.

a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;

Background And Aims: The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP.

Methods: Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing.

Results: Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p < 0.001), and different between the latter two groups (p < 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02-3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03-10.8)].

Conclusions: In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis.
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http://dx.doi.org/10.3109/00365521.2016.1161066DOI Listing
August 2016