PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations

Rare ATG7 genetic variants predispose patients to severe fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants

Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

107noNonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827-838)openopenPiscaglia F.; Svegliati-Baroni G.; Barchetti A.; Pecorelli A.; Marinelli S.; Tiribelli C.; Bellentani S.; Bernardi M.; Biselli M.; Caraceni P.; Domenicali M.; Garuti F.; Gramenzi A.; Lenzi B.; Magalotti D.; Cescon M.; Ravaioli M.; Del Poggio P.; Olmi S.; Rapaccini G.L.; Balsamo C.; Di Nolfo M.A.; Vavassori E.; Alberti A.; Benvegnau L.; Gatta A.; Giacomin A.; Vanin V.; Pozzan C.; Maddalo G.; Giampalma E.; Cappelli A.; Golfieri R.; Mosconi C.; Renzulli M.; Roselli P.; Dell'isola S.; Ialungo A.M.; Risso D.; Marenco S.; Sammito G.; Bruzzone L.; Bosco G.; Grieco A.; Pompili M.; Rinninella E.; Siciliano M.; Chiaramonte M.; Guarino M.; Camma C.; Maida M.; Costantino A.; Barcellona M.R.; Schiada L.; Gemini S.; Lanzi A.; Stefanini G.F.; Dall'aglio A.C.; Cappa F.M.; Suzzi A.; Mussetto A.; Treossi O.; Missale G.; Porro E.; Mismas V.; Vivaldi C.; Bolondi L.; Zoli M.; Granito A.; Malagotti D.; Tovoli F.; Trevisani F.; Venerandi L.; Brandi G.; Cucchetti A.; Bugianesi E.; Vanni E.; Mezzabotta L.; Cabibbo G.; Petta S.; Fracanzani A.; Fargion S.; Marra F.; Fani B.; Biasini E.; Sacco R.; Morisco F.; Caporaso N.; Colombo M.; D'ambrosio R.; Croce L.S.; Patti R.; Giannini E.G.; Loria P.; Lonardo A.; Baldelli E.; Miele L.; Farinati F.; Borzio M.; Dionigi E.; Soardo G.; Caturelli E.; Ciccarese F.; Virdone R.; Affronti A.; Foschi F.G.; Borzio F.Piscaglia, F.; Svegliati-Baroni, G.; Barchetti, A.; Pecorelli, A.; Marinelli, S.; Tiribelli, C.; Bellentani, S.; Bernardi, M.; Biselli, M.; Caraceni, P.; Domenicali, M.; Garuti, F.; Gramenzi, A.; Lenzi, B.; Magalotti, D.; Cescon, M.; Ravaioli, M.; Del Poggio, P.; Olmi, S.; Rapaccini, G. L.; Balsamo, C.; Di Nolfo, M. A.; Vavassori, E.; Alberti, A.; Benvegnau, L.; Gatta, A.; Giacomin, A.; Vanin, V.; Pozzan, C.; Maddalo, G.; Giampalma, E.; Cappelli, A.; Golfieri, R.; Mosconi, C.; Renzulli, M.; Roselli, P.; Dell'Isola, S.; Ialungo, A. M.; Risso, D.; Marenco, S.; Sammito, G.; Bruzzone, L.; Bosco, G.; Grieco, A.; Pompili, M.; Rinninella, E.; Siciliano, M.; Chiaramonte, M.; Guarino, M.; Camma, C.; Maida, M.; Costantino, A.; Barcellona, M. R.; Schiada, L.; Gemini, S.; Lanzi, A.; Stefanini, G. F.; Dall'Aglio, A. C.; Cappa, F. M.; Suzzi, A.; Mussetto, A.; Treossi, O.; Missale, G.; Porro, E.; Mismas, V.; Vivaldi, C.; Bolondi, L.; Zoli, M.; Granito, A.; Malagotti, D.; Tovoli, F.; Trevisani, F.; Venerandi, L.; Brandi, G.; Cucchetti, A.; Bugianesi, E.; Vanni, E.; Mezzabotta, L.; Cabibbo, G.; Petta, S.; Fracanzani, A.; Fargion, S.; Marra, F.; Fani, B.; Biasini, E.; Sacco, R.; Morisco, F.; Caporaso, N.; Colombo, M.; D'Ambrosio, R.; Croce, L. S.; Patti, R.; Giannini, E. G.; Loria, P.; Lonardo, A.; Baldelli, E.; Miele, L.; Farinati, F.; Borzio, M.; Dionigi, E.; Soardo, G.; Caturelli, E.; Ciccarese, F.; Virdone, R.; Affronti, A.; Foschi, F. G.; Borzio, F

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

Abstract Background No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. Aim of the study We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. Materials and methods The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. Results 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. Conclusions Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population