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1.
Purpose of Review
In this review, we examine the interaction between the metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and describe the impact of the features of MS on the most worrisome complications of non-alcoholic steatohepatitis (NASH), (cirrhosis, hepatocellular carcinoma) and, ultimately, on liver-related, cardiovascular, and overall mortality.Recent Findings
Insulin resistance, obesity, and dyslipidemia in a pro-inflammatory environment have a causal role in hepatic fibrogenesis and oncogenesis in NAFLD patients. Natural history, longitudinal studies confirm the conditions linked to MS as independent predictors of overall-, cardiovascular-, and liver-related mortality.Summary
Dysmetabolic factors stemming from insulin resistance play a key role in liver damage progression. Obesity, type 2 diabetes (T2DM), dyslipidemia, and arterial hypertension are independent predictors of liver fibrosis and cirrhosis; furthermore, obesity and T2DM play a key role in the development of hepatocellular carcinoma both in cirrhotic and non-cirrhotic NASH patients.2.
Ilaria Cavallari Alessia Delli Veneri Ernesto Maddaloni Rosetta Melfi Giuseppe Patti Nicola Napoli Paolo Pozzilli Germano Di Sciascio 《Current diabetes reports》2018,18(12):138
Purpose of the Review
To summarize available evidence regarding lipid-lowering interventions for the prevention of cardiovascular disease in patients with diabetes.Recent Findings
Statins and non-statin therapies that act through upregulation of LDL receptor expression are associated with similar cardiovascular risk reduction per decrease in LDL cholesterol.Summary
In subjects with diabetes, with or without established cardiovascular disease, each 39 mg/dl reduction in LDL cholesterol observed with statins is associated with a 21% relative reduction in the risk of major coronary events at 5 years. Statins remain the first-line lipid-lowering agents for the management of dyslipidemia in individuals with diabetes; however, the addition of non-statin therapies to lower LDL cholesterol, such as ezetimibe and PCSK-9 inhibitors, to maximally tolerated statin therapy is recommended in patients with atherosclerotic cardiovascular disease and baseline LDL cholesterol over 70 mg/dl. Recent data support even lower LDL cholesterol targets (<?55 mg/dl) to further reduce the risk of cardiovascular events especially in subjects with diabetes and documented cardiovascular disease.3.
Purpose of Review
To review the interactions between statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.Recent Findings
Statins are highly effective for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). However, statins also raise levels of PCSK9, a protein that increases circulating LDL-C levels by increasing LDL-C receptor degradation. Increases in PCSK9 levels also reduce the LDL-C response to statin therapy.Summary
The interactions between statins, PCSK9, LDL-C, and cardiovascular risk are multifaceted and are influenced by genetic, lifestyle, and environmental factors as well as lipid-lowering therapies.4.
Om Ganda 《Current diabetes reports》2018,18(11):126
Purpose of Review
Statins are the most evidence-based therapy to target LDL-C to reduce atherosclerotic events. Yet, many people are unable to achieve adequate reduction in this key atherogenic factor. Moreover, residual risk of cardiovascular events may persist even after “optimal” LDL-C due to elevations in triglyceride-rich lipoproteins. Therefore, additional therapies beyond statins are needed, particularly in patients with diabetes.Recent Findings
Clinical trials with ezetimibe and PCSK9 inhibitors have reported further reductions in cardiovascular events, beyond statins. The latter are particularly effective in lowering LDL-cholesterol and in reducing event rates. However, they are not effective in lowering triglycerides. Currently available fibrates and niacin have not proven effective in combination with statins in clinical trials, while the top line results of the REDUCE-IT trial with EPA, a pure omega-3 fatty acid, reporting 25% relative risk reduction in primary endpoints are of great interest.Summary
Recently approved agents have the promise to improve cardiovascular outcomes beyond statins. Many novel drugs in development have the potential to further improve prognosis.5.
Definition of terms
Under the term non-alcoholic fatty liver disease (NAFLD) both simple hepatic fat accumulation and non-alcoholic steatohepatitis (NASH) are combined. NASH is associated with liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).Epidemiological importance
In 2020, NAFLD will be the leading cause for liver transplantation in the USA, with rising financial costs for the healthcare system.Comorbidities, diagnosis, and treatment
Type 2 diabetes (T2D) and metabolic syndrome (MetS) are important risk factors for the development of NAFLD, whereby these three diseases share similar pathophysiologic conditions, e.g., insulin resistance, obesity, and metabolic inflammation. Due to the rising number of patients with T2D and MetS, clinicians should aim to diagnose NAFLD early in this patient population and if necessary start treatment.Goal
The aim of this work is to give an overview over the topic of NAFLD and diagnostic approaches in patients with T2D.6.
Hugo Ribeiro Zanetti Leonardo Roever Alexandre Gonçalves 《Current atherosclerosis reports》2018,20(2):9
Purpose of Review
This clinical update is intended to focus in relationship between HIV infection and use of antiretroviral therapy (ART) and statin.Recent Findings
Though ART significantly changed the course of HIV infection, it is related to numerous side effects principally to the lipid profile. In this way, statins became one of the most used lipid-lowering therapies in this population. In our clinical update, we evaluated studies that demonstrate the relationship and molecular mechanisms that HIV infection and ART use trigger dyslipidemia and also the use of statin to reduce this condition.Summary
We have demonstrated that use of statin can be used in dyslipidemic HIV-infected people as long as there is no drug interaction with ART. Recently, studies using rosuvastatin have shown greater effects when compared to the other statins.7.
Background
Decompensated liver cirrhosis is an important cause of mortality worldwide. Various modifiable and non-modifiable factors are involved in the pathogenesis of cirrhosis and its complications. This study was aimed to evaluate the association of iron overload and disease severity in patients of liver cirrhosis and its association with HFE gene mutation.Methods
Forty-nine patients with decompensated liver cirrhosis were recruited. Clinical and laboratory parameters were compared in patients with and without iron overload. C282Y and H63D gene mutation analysis was performed in all patients with iron overload.Results
Iron overload was found in 20 (40.82 %) patients. A significant positive correlation of transferrin saturation with Child-Turcotte-Pugh (CTP) score (r?=?0.705, p?<?0.001) and model for end-stage liver disease (MELD) score (r?=?0.668, p?<?0.001) was found. Transferrin saturation was also independently associated with high CTP and MELD score on multivariate analysis. Mortality over 3 months was significantly more common in iron-overloaded patients (p?=?0.028). C282Y homozygosity or C282Y/H63D compound heterozygosity was not found in any of the patients with iron overload.Conclusion
Iron overload was significantly associated with disease severity and reduced survival in patients of decompensated liver cirrhosis.8.
Purpose of Review
Dyslipidemia in patients with T2DM confers significant additional risk of adverse outcomes to patients with cardiovascular disease (CVD). These patients carry residual risk of adverse outcomes despite optimal management with conventional therapy such as lifestyle changes and statin therapy. The role of both nonstatin monotherapy in statin-intolerant patients and combination therapy with statins in patients with high risk of CVD events has been well studied. We sought to review the role of newer therapies in risk reduction in these patients.Recent Findings
Traditionally, non-statin options have included medications such as niacin, ezetimibe, fenofibrate, and n-3 fatty acids. Recently, drugs such as ezetimibe, inclisiran, and PCSK9 inhibitors have been studied with favorable results without an increased risk of developing new-onset diabetes. These medications hold the promise of increasing options to reduce cardiovascular risk in patients with T2DM.Summary
The role of newer non-statin therapies in patients with diabetic dyslipidemia in combination with statins needs to be further explored.9.
Purpose of the Review
As understanding of liver disease progression to cirrhosis has expanded, there has also been an acceleration in clinical trials and treatment options for the different underlying causes of cirrhosis to include chronic viral hepatitis, alcoholic and non-alcoholic fatty liver disease. It is imperative that healthcare practitioners fully appreciate the impact of liver disease and treatment from the patients’ and society perspective.Recent Findings
An important aspect of patient-reported outcomes (PROs) is assessment of health-related quality of life (HRQL) completed using generic or disease-specific instruments. In the past decades, substantial evidence has been complied that demonstrates development of cirrhosis which has a significant negative impact on a patients’ HRQL while effective treatment leads to significant gains in HRQL especially for patients with decompensated cirrhosis.Summary
Clinicians and clinical investigators must understand the importance of PROs for inclusion in clinical trials to fully assess the impact of cirrhosis on patients and the society.10.
Purpose of Review
The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings.Recent Findings
Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk.Summary
Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.11.
Shiran Shetty L Venkatakrishnan J Krishanveni Shantha Kumari 《Indian journal of gastroenterology》2017,36(1):23-26
Background
Alcoholic hepatitis and cirrhosis although part of spectrum of alcoholic liver disease can have overlapping features, and differentiating them using clinical, biochemical, and imaging features is not always possible. Standard therapy for each differs, and steroid therapy while beneficial in alcoholic hepatitis may be detrimental in cirrhosis due to high infectious complications. We analyzed our experience with liver biopsy in patients with severe alcoholic hepatitis.Methods
Male patients in the age group of 25–65 years who were clinically diagnosed with severe alcoholic hepatitis (DF > 32) were retrospectively analyzed and included in this study. All of them had undergone transjugular liver biopsy within the first 7 days of hospitalization.Results
Thirty patients were included. Most were in the 35–55 age group. Jaundice was present in all patients with fever and tender hepatomegaly also being common. On histopathological evaluation, 33.3% (n = 10) suspected clinically to have alcoholic hepatitis had underlying cirrhosis.Conclusion
Cirrhosis is found in one third of patients with severe alcoholic hepatitis. This may alter our approach to management of this condition.12.
Ashish Joshi Sushil Falodia Naveen Kumar Pawan Gupta P. C. Khatri 《Indian journal of gastroenterology》2018,37(3):243-247
Background
Liver involvement in celiac disease (CD) is classified into autoimmune and cryptogenic. The association between CD and autoimmune liver diseases like autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis is well-established; however, the data on patients with cryptogenic cirrhosis, particularly from India, are scanty. So we did this study to find the prevalence of CD in patients with cryptogenic cirrhosis.Methods
This was a prospective observational study, involving children of less than 18 years old attending Pediatric and Gastroenterology clinic with a diagnosis of cryptogenic cirrhosis. The patients were evaluated for CD and divided into two groups: chronic liver disease (CLD) with CD, and CLD without CD. Both the groups were followed up for 6 months. CLD with CD group was treated with gluten-free-diet (GFD) and CLD without CD group was followed up without any specific intervention except standard care of CLD.Results
Out of 84 patients, 11 (13.1%) were diagnosed as CLD with CD. There was an improvement in hemoglobin levels, liver function tests, and Child-Pugh score after initiation of GFD in CLD with CD group.Conclusion
The prevalence of CD in cryptogenic cirrhosis was 13.1%. Screening for CD is recommended for cryptogenic cirrhosis. Hepatic functions improve with a GFD in CD patients with cirrhosis.13.
A. F. H. Pfeiffer 《Der Diabetologe》2016,12(7):468-472
Background
Disturbances of glucose metabolism are common in chronic liver disease and about 30–40?% of patients with liver cirrhosis develop type 2 diabetes. The diabetes may be a direct consequence of the hepatic disease due to excessive insulin resistance or may be caused by classical type 2 diabetes.Blood glucose determination
Patients with chronic liver disease frequently have a normal fasting glucose despite manifest type 2 diabetes with postprandial excessive increases in glucose. Therefore, oral glucose tolerance tests should be performed after diagnosis of hepatic cirrhosis.Prognosis
Diabetes mellitus is associated with increased mortality and an increased risk of complications of liver cirrhosis including premature death, hepatocellular carcinoma, hepatic encephalopathy, and spontaneous bacterial peritonitis. Therapy of diabetes should include metformin and α?glucosidase inhibitors which can reduce the risk of these complications. Therefore, the diagnosis of diabetes has important consequences in chronic liver disease.14.
Daisuke Takada Keiichi Sumida Akinari Sekine Ryo Hazue Masayuki Yamanouchi Tatsuya Suwabe Noriko Hayami Junichi Hoshino Naoki Sawa Kenmei Takaichi Takeshi Fujii Kenichi Ohashi Yoshifumi Ubara 《BMC nephrology》2017,18(1):362
Background
Various renal manifestations are known to develop in patients with liver disease, including chronic hepatitis and cirrhosis.Case presentation
We evaluated renal disease in two 47-year-old Japanese men with liver cirrhosis and chronic alcoholism for 34 years and 27 years, respectively. Renal biopsy demonstrated massive wire loop-like deposits in the subendothelial space of the glomerular basement membrane and in the mesangium. However, immunofluorescence was only positive for IgA and C3, and electron microscopy did not reveal any organized structures in the electron-dense deposits. IgA nephropathy was diagnosed, although the features were different from primary IgA nephropathy. Both patients had portosystemic shunts associated with liver cirrhosis. Their renal deposits and proteinuria resolved completely after 1 year of steroid therapy.Conclusion
Alcohol abuse may have contributed to development of secondary IgA nephropathy in these two patients, probably via their portosystemic shunts.15.
Guido Stirnimann Maryam Ebadi Puneeta Tandon Aldo J. Montano-Loza 《Current gastroenterology reports》2018,20(11):50
Purpose of Review
The purpose of this review is to discuss the current evidence regarding the impact of sarcopenia on patients with cirrhosis awaiting liver transplantation and to determine if its presence should be considered a criterion for expedited transplantation or a contraindication for transplantation.Recent Findings
Sarcopenia is a negative predictor of survival in patients on a waiting list and after liver transplant. The gut-liver axis and the liver-muscle axis have been explored to understand the complex pathophysiology of sarcopenia.Summary
Sarcopenia is a frequent finding in patients with cirrhosis. The diagnosis is ideally based on cross-sectional image analysis (CT or MRI) and treatment consists of optimization of caloric and protein intake. To date, prioritizing tools for liver transplantation have not included nutrition or sarcopenia parameters. Patients with a low Model for End-Stage Liver Disease (MELD) or MELD-Na score and sarcopenia would benefit from prioritization for transplant in order to reduce time on waiting list and therefore mortality.16.
Joao Miguel Serigado Katherine C. Barboza Paula Marcus Samuel H. Sigal 《Current hepatitis reports》2018,17(1):22-32
Purpose of Review
Depression is the most commonly diagnosed psychiatric illness. It is prevalent in most chronic medical conditions and is associated with increased morbidity and mortality. Depression is especially common in patients with cirrhosis.Recent Findings
In this review, we discuss the prevalence, risk factors, diagnosis, clinical impact, and treatment of depression in cirrhosis. We describe various screening tests important for diagnosis, the interaction of depression with hepatic encephalopathy, and its significant impact on medication adherence, mortality, and caregiver burden.Summary
These findings highlight the importance of appropriate screening, diagnosis, and treatment of depression in patients with cirrhosis.17.
Background
The prevalence of nonalcoholic fatty liver disease (NAFLD) continues to increase. An estimated 25?% of the adult population worldwide and more than 50?% of patients with type 2 diabetes or obesity have NAFLD.Objectives
An overview of the natural history and complications of NAFLD is provided.Materials and methods
Following an extensive literature research, the current guidelines, expert opinions and studies focusing on NAFLD were analyzed.Results
The term NAFLD includes the entities nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which are defined by histological parameters. Importantly, “benign” NAFL may progress towards more aggressive NASH with the development of liver fibrosis. The grade of fibrosis is the most important predictor for overall and liver-related mortality in NAFLD patients and patients suffering from type 2 diabetes mellitus have a higher risk for progressive fibrosis. Progressive NAFLD can develop into liver cirrhosis with the potential of fatal complications of portal hypertension and liver failure. Notably, hepatocellular carcinoma may also develop in noncirrhotic NAFLD. Furthermore, NAFLD is an independent risk factor for cardiovascular disease and extrahepatic malignancy, which represent the two most frequent causes of death in NAFLD patients. To date, a lifestyle intervention aiming at weight reduction and increased physical activity is the first-line therapy for NAFLD.Conclusions
NAFLD is one of the most common liver diseases and is associated with relevant hepatic and extrahepatic morbidity and mortality.18.
Tommaso Stroffolini Evangelista Sagnelli Caterina Sagnelli Maurizio Russello Massimo De Luca Floriano Rosina Bruno Cacopardo Giuseppina Brancaccio Caterina Furlan Giovanni Battista Gaeta Anna Licata Piero Luigi Almasio behalf of EPACRON study group 《Infection》2017,45(3):277-281
Background
The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades.Aim
To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies.Methods
A cross-sectional study involving 16 referral centres scattered all over the country in 2014.Results
Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geographical area of residence. The presence of liver cirrhosis was diagnosed in 52.4% of cases. In comparison to previous studies, a further shift towards the oldest age groups and an increasing proportion of subjects having liver cirrhosis among all anti-delta-positive subjects are observed.Conclusions
Currently, hepatitis delta infection mostly affects old people who have an advanced but indolent liver disease, reflecting a survival effect. The defective hepatitis delta virus is near to disappear in the country, where it has been discovered in the second half of 70s.19.
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