Statins and non-alcoholic fatty liver disease

Dear Editor, In April 9 issue, van den Berg et al1 report interesting results on the indication for lipid‐lowering treatment in a large cohort with suspected non‐alcoholic fatty liver disease (NAFLD) within the population‐based Lifelines Cohort Study. Fatty liver index (FLI) ≥60 was used as a proxy of NAFLD and the NAFLD fibrosis score (NFS) to identify the NAFLD patients with suspected advanced fibrosis. Cardiovascular disease (CVD) risk was established by the 2016 European society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias.2 Subjects with FLI ≥ 60 (suspected NAFLD) had an increased 10‐ year predicted cardiovascular risk compared to those with FLI < 60 with an approximately 2 times higher need for statin therapy based on CVD risk prediction and their LDL cholesterol level. Subjects with a FLI ≥ 60 were more likely to be classified with type 2 diabetes, Metabolic Syndrome (MetS), history of CVD and impaired renal function. Interestingly, estimated 10‐year very high cardiovascular risk was approximately 4 times higher in subjects with a NFS > 0.676 compared to those with the absence of advanced fibrosis. Finally, indication for statin treatment was positively associated with a FLI ≥ 60 after controlling for age, sex, current smoking, impaired renal function, and the presence of MetS and its individual components. The above results have an even greater relevance if we consider that all the subjects who were already on statin therapy were subtracted from the analysis. These findings may have an important clinical relevance and emphasize the need for effective treatment with statins in patients with NAFLD. Indeed, accumulating evidence suggests that CVD, rather than liver disease, dictates the outcomes in NAFLD.3 Besides, in most subjects NAFLD constitutes the hepatic component of MetS and numerous patients have atherogenic dyslipidemia. This study further supports the results of a previous study by our group where under prescription of statins in patients with NAFLD was observed.4 In fact, mild liver enzyme elevation remains a concern and despite its proven efficacy and safety,5 statin administration is sometimes limited by the worry about related side effects. Indeed, there is a tendency of general physicians to discourage statin use in patients with baseline elevation of serum liver enzymes and/ or to discontinue medication when minor alterations were appreciated. Of note, in our study, statin under‐use was high also in patients at very high CV risk such as those with a previous CV event. This study by van den Berg et al further stresses the issue of under prescription of statins in people with NAFLD and indication for treatment, based on CV risk class and low‐density lipoprotein cholesterol target according to ESC/EAS guidelines

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p < 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p < 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Hepatocellular carcinoma in children: Hepatic resection and liver transplantation

Hepatocellular carcinoma (HCC) is a rare malignancy in children and at the time of diagnosis up to 80% of pediatric HCC are unresectable due to large and multiple lesions. The majority of pediatric HCC occurs on a background of normal liver, and consequently the absence of concomitant chronic liver disease generally allows tolerating pre-and post-operative chemotherapy. Based on the large experiences of adult HCC and pediatric hepatoblastoma, in the last years a multidisciplinary aggressive treatment composed of surgical resection and chemotherapy (based on cisplatin and doxorubicin) has been proposed, improving patient outcomes and recurrence rate in children with HCC. However, the overall survival rate in children with HCC is not satisfactory yet; while the 5-year survival rate may achieve up to 70-80% in non-metastatic resectable HCC, it remains &lt;20% in children with unresectable HCC. The mainstay of the pediatric HCC therapeutic strategy is the radical tumor resection, weather by hepatic resection or liver transplantation, nevertheless the best surgical approaches as well as the optimal neoadjuvant and adjuvant treatment are still under debate. Different strategies have been explored to convert unresectable HCC into resectable tumors by extending criteria for surgical treatment and/or associating multi-modal treatments, such as systemic and local-regional therapy, but universal recommendation needs to be defined yet. The purpose of this review is to outline the role of different surgical approaches, including hepatic resection and liver transplantation, in pediatric HCC with or without underlying chronic liver disease

Brazilian Coffee Quality: Cultural, Microbiological and Bioactivity Aspects

The Brazilian coffee industry attentive to the regrouping of the consumers in relation to the notion of quality of the coffee and that this is depends on multiple determinants one must consider factors that involve the steps from pre-harvest to storageundergoes a deep transformation in all coffee chain. Good practice programs, applied along the productive process has repercussion on the microbiological, physical and chemical characteristics translated by the quality of the final product regarding the sensorial and safety standards. Research has been progressively pursuing the improvement of quality techniques and producers have been proactive in all stages of productivity and industrialization, readily absorbing the new technologies generated by the research. Thus, production standards have been designed according to the world demands of quality in a holistic way that involves in addition to the quality of the final product, the quality of the activity by socio-environmental aspects

Dietary fat intake as a risk factor for the development of diabetes. Multinational, multicenter study of the Mediterranean Group for the Study of Diabetes (MGDS)

In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes(RDM),42subjectswithundiagnoseddiabetes(UDM)(AmericanDiabetesAssociation criteria—fasting plasma glucose [FPG] 126 mg/dl), and 55 subjects with impaired fasting glucose(IFG)(FPG 110and126mg/dl).Eachgroupwascomparedwithacontrolgroupof nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS— Compared with control subjects, RDM more frequently had a family history of diabetes(49.0vs.14.2%;P0.001),exercisedless(exerciseindex53.5vs.64.4;P0.01),and more frequently had sedentary professions (47.5 vs. 27.4%; P 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P 0.05), whereas total fat (30.2 0.5 vs. 27.8 0.5%; P 0.001) and animal fat (12.2 0.3 vs. 10.8 0.3%; P 0.01) contributed moreandtheplant-to-animalfatratiowaslower(1.50.1vs.1.80.1;P0.01).UDMmore frequentlyhadafamilyhistoryofdiabetes(38.1vs.19.0%;P0.05)andsedentaryprofessions (58.5vs.34.1%;P0.05),carbohydratescontributedlesstotheirenergyintake(47.61.7vs. 52.81.4%;P0.05),totalfat(34.71.5vs.30.41.2%;P0.05)andanimalfat(14.2 0.9 vs. 10.6 0.7%; P 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 0.2 vs. 2.3 0.4; P 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P 0.05). CONCLUSIONS— Our data support the view that increased animal fat intake is associated with the presence of diabetes