Publications by authors named "Antonio Picardi"

91 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 May 18;35(5):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
May 2021

Steroid-refractory immune related hepatitis may hide viral re-activation.

Future Sci OA 2020 Aug 6;6(9):FSO614. Epub 2020 Aug 6.

Department of Medical Oncology, Campus Bio-Medico University, Via Alvaro del Portillo 200, Rome, Italy.

Cancer immunotherapy has become a stronghold in modern oncology. Immune checkpoint inhibitors, in particular anti-PD-1 and anti-PD-L1 antibodies, are approved for the treatment of several solid cancers. In the near future, an increasing number of patients will be eligible for immunotherapy. Therefore, the management of immune-related adverse events is a daily challenge in clinical practice, among which hepatic immune-related toxicity has been described as a rare adverse event. We report the case of a patient treated with nivolumab (an anti-PD-L1 antibody) for a stage IV resected melanoma who developed recurrence of steroid-refractory liver toxicity that was later discovered to be associated with acute exacerbation of chronic undiagnosed hepatitis B. The patient significantly benefited from antiviral treatment. We conclude that serological viral screening is strongly recommended before starting immune checkpoint inhibitor treatment.
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http://dx.doi.org/10.2144/fsoa-2020-0056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668132PMC
August 2020

Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis.

Curr Drug Metab 2020 ;21(11):866-884

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

Background: Hepatocellular carcinoma (HCC) is among the world's most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).

Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways.

Methods: The Food and Drug Administration (FDA)'s and European Medicines Agency (EMA)'s datasheets, results from clinical trials and observational studies have been reviewed.

Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients.

Conclusion: The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.
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http://dx.doi.org/10.2174/1389200221999200918141239DOI Listing
January 2020

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

An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase.

Am J Physiol Gastrointest Liver Physiol 2020 10 19;319(4):G469-G480. Epub 2020 Aug 19.

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

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity. During NAFLD, hepatic fat metabolism is impaired at several levels, which is significantly contributed to by impaired lipophagy, in which reduced LAL activity may play an important role. For further research and intervention in NAFLD, targeting LAL activity may provide interesting perspectives.
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http://dx.doi.org/10.1152/ajpgi.00049.2020DOI Listing
October 2020

Lipophagy Impairment Is Associated With Disease Progression in NAFLD.

Front Physiol 2020 17;11:850. Epub 2020 Jul 17.

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

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is associated with aging and features of metabolic syndrome. Lipotoxicity and oxidative stress are consequent to dysregulation of lipid metabolism and lipid accumulation, leading to hepatocyte injury and inflammation. Lipophagy consists in selective degradation of intracellular lipid droplets by lysosome and mounting evidence suggests that lipophagy is dysregulated in NAFLD. Here we demonstrate lipophagy impairment in experimental models of NAFLD and in a NAFLD patient cohort by histomorphological and molecular analysis. High fat diet-fed C57BL/6J male mice and high-fat/high-glucose cultured Huh7 cells showed accumulation of both p62/SQSTM1 and LC3-II protein. In 59 NAFLD patients, lipid droplet-loaded lysosomes/lipolysosomes and p62/SQSTM1 clusters correlated with NAFLD activity score (NAS) and with NAS and fibrosis stage, respectively, and levels of expression of lysosomal genes, as well as autophagy-related genes, correlated with NAS and fibrosis stage. An increased amount of lipid droplets, lipolysosomes and autophagosomes was found in subjects with NAFLD compared to healthy subjects at ultrastructural level. In conclusion, here we observed that NAFLD is characterized by histological, ultrastructural and molecular features of altered autophagy that is associated with an impaired lipid degradation. Impaired autophagy is associated with features of advanced disease. Lipopolysosomes, as individuated with light microscopy, should be further assessed as markers of disease severity in NAFLD patients.
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http://dx.doi.org/10.3389/fphys.2020.00850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380071PMC
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

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

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

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables.

World J Gastroenterol 2018 Nov;24(43):4835-4845

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

Non-alcoholic fatty liver disease (NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma (HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism (SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis (NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
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http://dx.doi.org/10.3748/wjg.v24.i43.4835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250919PMC
November 2018

Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis.

J Viral Hepat 2018 12 6;25(12):1493-1500. Epub 2018 Sep 6.

Liver and Transplant Unit, Tor Vergata University Hospital, Rome, Italy.

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.
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http://dx.doi.org/10.1111/jvh.12982DOI Listing
December 2018

The role of intestinal microbiota in the pathogenesis of NAFLD: starting points for intervention.

Arch Med Sci 2018 Apr 23;14(3):701-706. Epub 2016 Mar 23.

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

In recent years, close links between intestinal microbiota and host metabolism have been recognized. Intestinal bacteria can participate in the extraction of calories from food, and circulation of bacterial products, in particular lipopolysaccharides (LPS), is responsible for the "metabolic endotoxemia", which contributes to insulin resistance and its complications, such as non-alcoholic fatty liver disease (NAFLD). Indeed, qualitative and quantitative intestinal dysbiotic changes have been clearly documented in NAFLD patients, and several mechanisms by which the intestinal microbiota can directly promote liver fat deposition, inflammation and fibrosis have also been described. Consistently, although with some differences concerning type and proportion of results, experimental and clinical studies are quite concordant in demonstrating beneficial effects of probiotic and/or prebiotic therapy in NAFLD. Although some physiopathological bases have been produced, major doubts still remain concerning how and when to intervene. Indeed, most of the available works were performed with mixtures of probiotics and/or prebiotics, and a baseline assessment of dysbiosis aimed at selecting the best candidates for treatment and predicting response has not been performed in any of the clinical studies in NAFLD. While future research is expected to solve these issues, the particularly favorable safety profile suggests that probiotic/prebiotic therapy could already be "tested" in NAFLD patients on an individual basis, at least once all the measures recommended by the latest guidelines have failed.
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http://dx.doi.org/10.5114/aoms.2016.58831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949899PMC
April 2018

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

Impairment of GH/IGF-1 Axis in the Liver of Patients with HCV-Related Chronic Hepatitis.

Horm Metab Res 2018 02 18;50(2):145-151. Epub 2017 Sep 18.

Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy.

Resistance to the action of growth hormone (GH) frequently complicates liver cirrhosis, while, physiologically, the activation of GH receptor (GHR) determines phosphorylation of signal transducer and activator of transcription (STAT)-5 and the consequent induction of insulin-like growth factor-1 (IGF-1) expression. The suppressor of cytokine signaling (SOCS)-3 negatively regulates this intracellular cascade. We aimed to evaluate the hepatic expression of the GH/IGF-1 axis components in the liver of patients with HCV-related chronic hepatitis at different fibrosis stages. The expression of GH/IGF-1 axis components, such as GHR, IGF-1, STAT5-p, and SOCS-3, was assessed by immunohistochemistry at the lobular level in 61 patients with HCV-related hepatitis. At the hepatocyte level, IGF-1 and nuclear STAT5-p positivity scores showed negative correlations with fibrosis stage, while SOCS-3 score a positive one (p<0.05 for all). Furthermore, the reduction of hepatocyte score of IGF-1 expression was associated with the serological parameters of liver damage (p<0.05) and with the increase of the score of IGF-1 expression by hepatic stellate cells (p<0.05). IGF-1 expression by hepatocytes was reduced with fibrosis progression, probably due to the impairment of GHR intracellular cascade by the SOCS-3 activation already in pre-cirrhotic stages. The inverse correlation between IGF-1 expressed by hepatocytes and by hepatic stellate cells suggests that IGF-1 may exert specific functions in different hepatic cells.
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http://dx.doi.org/10.1055/s-0043-118911DOI Listing
February 2018

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

Reelin expression in human liver of patients with chronic hepatitis C infection.

Eur J Histochem 2017 Mar 17;61(1):2745. Epub 2017 Mar 17.

Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy.

Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA) were also evaluated. As further confirmed by co-localization experiments (Reelin +CRBP-1), Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002). Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002), but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1), a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data.
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http://dx.doi.org/10.4081/ejh.2017.2745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365015PMC
March 2017

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

The Liver as Another Possible Target Organ for Infection.

Case Rep Infect Dis 2016 29;2016:7438972. Epub 2016 Nov 29.

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

A case of liver abscess due to infection in an immunocompetent 59-year-old man is reported. Percutaneous drainage and antimicrobial therapy, with vancomycin and levofloxacin afterwards, have been demonstrated to be an appropriate treatment, leading to clinical and radiological cure.
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http://dx.doi.org/10.1155/2016/7438972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153463PMC
November 2016

Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy.

World J Hepatol 2016 Oct;8(29):1244-1250

Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Alessandro Guidi, Antonio Picardi, Unit of Internal Medicine and Hepatology, Department of Medicine, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases.
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http://dx.doi.org/10.4254/wjh.v8.i29.1244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067444PMC
October 2016

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

Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience.

World J Hepatol 2016 Aug;8(22):949-56

Luigi Elio Adinolfi, Barbara Guerrera, Internal Medicine Unit, Second University of Naples, 80125 Marcianise, Italy.

Aim: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings.

Methods: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL).

Results: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age.

Conclusion: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.
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http://dx.doi.org/10.4254/wjh.v8.i22.949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976214PMC
August 2016

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

Breath-print analysis by e-nose for classifying and monitoring chronic liver disease: a proof-of-concept study.

Sci Rep 2016 05 5;6:25337. Epub 2016 May 5.

Clinical Medicine and Hepatology Department, Campus Bio-Medico University, via Alvaro del Portillo 200, 00128 Rome, Italy.

Since the liver plays a key metabolic role, volatile organic compounds in the exhaled breath might change with type and severity of chronic liver disease (CLD). In this study we analysed breath-prints (BPs) of 65 patients with liver cirrhosis (LC), 39 with non-cirrhotic CLD (NC-CLD) and 56 healthy controls by the e-nose. Distinctive BPs characterized LC, NC-CLD and healthy controls, and, among LC patients, the different Child-Pugh classes (sensitivity 86.2% and specificity 98.2% for CLD vs healthy controls, and 87.5% and 69.2% for LC vs NC-CLD). Moreover, the area under the BP profile, derived from radar-plot representation of BPs, showed an area under the ROC curve of 0.84 (95% CI 0.76-0.91) for CLD, of 0.76 (95% CI 0.66-0.85) for LC, and of 0.70 (95% CI 0.55-0.81) for decompensated LC. By applying the cut-off values of 862 and 812, LC and decompensated LC could be predicted with high accuracy (PPV 96.6% and 88.5%, respectively). These results are proof-of-concept that the e-nose could be a valid non-invasive instrument for characterizing CLD and monitoring hepatic function over time. The observed classificatory properties might be further improved by refining stage-specific breath-prints and considering the impact of comorbidities in a larger series of patients.
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http://dx.doi.org/10.1038/srep25337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857073PMC
May 2016