Preop Factors Affect CVD Risk After Liver Transplantation

Medscape Medical News > Conference News

Neil Osterweil
November 09, 2014

BOSTON — A review of data on nearly 33,000 liver transplant recipients suggests that some modifiable pretransplant risk factors can account for major adverse cardiovascular events in the first 3 months after surgery.

"What was most interesting to us was that the thromboembolic diseases, which we tend to screen for very closely — pulmonary embolism, myocardial infarction — only accounted for about 7% to 10% of all cases of cardiovascular complications," Lisa VanWagner, MD, a gastroenterology and hepatology fellow at the Northwestern University Feinberg School of Medicine in Chicago.

Before transplantation, "we rigorously evaluate our candidates cardiovascularly, but we focus on coronary disease in our risk stratification, so patients get stress echocardiograms and coronary catheterization. What we tend to forget about are these subclinical changes, that idea of cirrhotic cardiomyopathy, the arrhythmic potential, and the chronotropic incompetence that happens in cirrhosis of the heart, which is the inability to mount a response to stress," she told Medscape Medical News.

Cardiovascular events — including myocardial infarction, heart failure, pulmonary embolism, atrial fibrillation, cardiac arrest, and stroke — are among the leading causes of complications after transplantation, and are associated with worse overall survival in the first year after transplantation.

Dr VanWagner and colleagues created a database to assess the prevalence and predictors of major adverse cardiovascular events in the first few months after transplantation.

They did so by identifying adults who underwent a primary liver transplant from February 2002 to December 2012 in a member institution of the University Health System Consortium, and matching them to recipients in the Organ Procurement and Transplantation Network registry. They used billing codes to assess comorbidities and the incidence of 30- and 90-day major cardiovascular events.

Of the 32,810 patients they identified, 4400 were admitted to a hospital within 30 days of transplantation, and 6095 were admitted within 90 days. Of the patients admitted in the first month, 330 (7.4%) had a major adverse cardiovascular event; of those admitted in the first 3 months, 429 (7.0%) had a major adverse cardiovascular event.

The most common causes of 30- and 90-day adverse events were atrial fibrillation, heart failure, and pulmonary embolism.

Patients who experienced a major adverse cardiovascular event were significantly more likely than other recipients to have alcoholic liver disease or nonalcoholic steatohepatitis as the primary indication for transplantation (P = .0003). They were also more likely to have a higher mean calculated Model for End-Stage Liver Disease score (P = .001), and to have a cardiovascular comorbidity present at the time of transplantation. Significant cardiovascular comorbidities were heart failure (P < .0001), ischemic heart disease (P < .0001), hypertension (P = .05), stroke (P = .001), and atrial fibrillation (P < .0001).

Other significant comorbidities were chronic kidney disease, hepatopulmonary syndrome, and asthma or chronic obstructive pulmonary disease.

On multivariate regression analysis, factors that independently predicted any major adverse cardiovascular event within 90 days included age older than 45 years (incidence rate ratio [IRR], 1.8; 95% confidence interval [CI], 1.2 - 2.7), alcoholic cirrhosis (IRR, 1.6; 95% CI, 1.2 - 2.2), nonalcoholic steatohepatitis (IRR, 1.6; 95% CI, 1.2 - 2.2), a high pretransplant level of creatinine (IRR, 1.1; 95% CI, 1.04 - 1.2), atrial fibrillation (IRR, 6.9; 95% CI, 4.9 - 9.6), and stroke (IRR, 6.3; 95% CI, 1.6 - 25.4).

Major adverse cardiovascular events were also associated with significantly worse 1-year survival (75.2% vs 85.6%; P < .0001).

These findings suggest an opportunity to improve care for liver transplant candidates and enhance recipient selection, said Dr VanWagner.

Certainly alcohol damages the liver, but it also damages the heart.

A gastroenterologist who was not involved in the study told Medscape Medical News that cardiovascular complications are a major problem and have a serious effect on outcomes in patients undergoing liver transplantation.

The investigators "have done a wonderful job looking at risk predictors of complications and describing the major problems that are occurring in the early days after transplantation," said Simon Robson, MD, chief of the division of gastroenterology at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, both in Boston.

Dr Robson said that the associations the investigators found between postoperative cardiovascular risk and fatty liver disease and alcoholic cirrhosis are particularly important.

"With hepatitis C being eradicated, most of the patients we're going to be transplanting in the next two decades fall into these categories, and in Europe, most of the patients are alcoholic right now. Certainly alcohol damages the liver, but it also damages the heart," he said.

The study was supported by the National Heart, Lung, and Blood Institute; the American Liver Foundation; and the AASLD Foundation. Dr VanWagner and Dr Robson have disclosed no relevant financial relationships.

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD). Abstract 549. Presented November 8, 2014.

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More Evidence That Non-Alcoholic Fatty Liver Disease is an Independent Cardiovascular Risk Factor

Embargoed until 6am on Thursday 10 April 2014

London, UK, Thursday 10 April 2014: Two new studies presented today at the International Liver Congress^TM 2014 have provided more evidence to clarify the role of non-alcoholic fatty liver disease (NAFLD) as an independent risk factor for the development of cardiovascular disease (CVD).

In the first long-term study^[1], in patients at high CVD risk, NAFLD was shown to contribute to the progression of early atherosclerosis independently of traditional CVD risk factors. In a second long-term study^[2], NAFLD was confirmed as a significant long-term risk factor for the development of diabetes mellitus (DM). Importantly, those patients showing signs of an improvement in the fatty appearance of their liver in response to treatment then had a reduced risk of going on to develop diabetes. 

NAFLD describes a range of conditions where there is a build-up of fat in the liver cells in people who do not drink alcohol excessively. It is rapidly becoming the most common liver disease worldwide, particularly so in the Western world with an estimated prevalence of 20 – 30%. In many cases, NAFLD is linked to being obese or overweight.

Presenting the results of these two studies, EASL’s Educational Councillor Professor Jean-Francois Dufour of the University Clinic for Visceral Surgery and Medicine, University of Bern, Switzerland said: “We now have a strong body of evidence that NAFLD may pose a CVD risk above and beyond that conferred by traditional CVD risk factors, such as dyslipidemia, diabetes and smoking. This means that healthcare providers managing patients with NAFLD should take this factor into account in the CVD risk stratification, although the best way to implement this remains to be defined,” he added.

NAFLD an early independent predictor of carotid atherosclerotic disease

In a long-term study, patients with NAFLD had a higher prevalence of carotid plaques (44 vs. 37%; p< 0.001), a higher carotid intima-media thickness (C-IMT) (0.64±0.14 vs. 0.61±0.13; p< 0.001), and a higher Framingham score, which measured their 10-year CVD risk (15±9% vs. 8±7%; p< 0.001).

The presence of NAFLD also predicted whether that patient had thickening of the carotid intima-media (beta=0.037; p=0.005), and evidence of early carotid plaques (OR=1.21; 95%CI: 1.03-1.42; p=0.02), independently of the patients’ age, sex, BMI, hypertension and tobacco use.

C-IMT significantly increased in those patients who developed signs of NAFLD (0.60±0.13 to 0.64±0.14; p=0.01). Using a Cox model, NAFLD at baseline predicted the occurrence of carotid plaques (OR=1.27; 95%CI: 1.009-1.613; p< 0.05), independently of age, sex, diabetes and high BP.

“Whether NAFLD is incidentally or causally associated to early carotid atherosclerosis has previously been the subject of much debate,” said Professor Dufour. “While there are case-control studies that have demonstrated a significant and independent relationship between NAFLD and carotid atherosclerotic disease, up until now, long-term follow-up data have been missing.”

Patients recruited to this study had more than two CVD risk factors without previous CVD events, known liver disease, and drinking < 50g of alcohol/day. C-IMT was measured using carotid ultrasonography with carotid plaques defined as C-IMT>1mm at the carotid bifurcation. Results were validated in a long-term follow-up cohort of patients with two C-IMT measurements at >1-year interval.

The Fatty Liver Index (FLI), a surrogate marker of hepatic steatosis when ≥60 years old, and the Framingham cardiovascular risk score (FRS) were calculated.

5,671 patients underwent at least one C-IMT measurement: 52% males; mean age 52±11years; mean BMI = 26.1±4.7; 33% NAFLD; 39% CP, mean C-IMT 0.62±0.13mm. 1,872 patients had 2 C-IMT measurements.

During the 8±4 year follow-up, NAFLD occurred in 12% and carotid plaques in 22% of the patients.

Improvement of NAFLD is associated with a reduced risk of developing DM

A 10-year longitudinal study has confirmed that NAFLD is a significant risk factor for the development of diabetes, and improvement of NAFLD through treatment is associated with a reduced risk of developing diabetes (in submission).

In this study of 3,074 Japanese patients, 117 participants (16.1%) in the NAFLD group developed diabetes during a 10 year follow-up period, compared to only 72 participants (3.1%) in the non-NAFLD group (p< 0.001). The multivariate odds ratio was 2.82 (95% confidence interval: 1.91-4.15) in the NAFLD group compared to the non-NAFLD group.

Moreover, 7 participants (6.4%) in the improved group developed diabetes compared to 110 participants (17.8%) in the non-improved group. In the improved group, the multivariate odds ratio was 0.30 (95% CI: 0.13-0.66), in comparison to the non-improved group.

“Evidence from previous longitudinal studies has demonstrated a clear link between NAFLD and the development of DM,” said Professor Dufour. “However, this is the first study to show that DM can be prevented if NAFLD is improved,” he explained.

“A multidisciplinary approach is therefore required in the treatment of NAFLD patients, taking into account the presence of NAFLD as a critical part of diabetes prevention and care. New clinical trials to investigate the beneficial effects of anti-diabetes drugs on NAFLD histology, and the potential impact of anti-diabetes drugs on diabetes incidence and cardiovascular risk in non-diabetic patients with early-stage NAFLD are now underway,” Professor Dufour concluded.

8,070 participants who had a health check twice between 2000 and 2012 with 10 years between each check were enrolled into this study. An inclusion criterion included having had abdominal ultrasounds during the first and second visits. Exclusion criteria included alcohol use ≧20g/day, positive HBs antigen, positive HCV antibody, and diabetes mellitus at baseline.

The 3,074 eligible participants were divided into the NAFLD group (n=728) and non-NAFLD group (n=2,346), according to ultrasonography-detected fatty liver.

The NAFLD group was then further categorised into the improved group (n=110) and non-improved group (n=618), based on fatty liver disappearance at the second health check. Multivariate odds ratios for the development of DM were estimated by a logistic regression model.

Disclaimer: the data referenced in this release is based on the submitted abstracts. More recent data may be presented at the International Liver Congress™ 2014.

- Ends -

Notes to Editors

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL’s main focus on education and research is delivered through numerous events and initiatives, including:

• The International Liver Congress^TM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of Hepatology
• Journal of Hepatology published monthly
• Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
• Participation in a number of policy initiatives at European level

About The International Liver Congress^TM 2014

The International Liver Congress™ 2014, the 49th annual meeting of the European Association for the study of the Liver, is being held at ExCel London from April 9 – 13, 2014. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:

Email: easlpressoffice@cohnwolfe.com

Helena Symeou  +44 7976 562 430

Courtney Lock +44 7894 386 422

[1] R.Pais et al. NAFLD IS AN INDEPENDENT PREDICTOR OF EARLY CAROTID ATHEROSCLEROSIS: RESULTS FROM A LARGE TRANSVERSAL STUDY AND LONG-TERM FOLLOW-UP VALIDATION COHORT. Abstract presented at the International Liver Congress^TM 2014

[2] H.Yamazaki et al. DECREASED DEVELOPMENT OF DIABETES MELLITUS WITH IMPROVEMENT OF NONALCOHOLIC FATTY LIVER DISEASE: A 10-YEAR JAPANESE COHORT STUDY Abstract presented at the International Liver Congress^TM 2014

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Antivirals for HCV improve kidney and cardiovascular diseases in diabetic patients

PUBLIC RELEASE DATE: 11-Dec-2013

Contact: Dawn Peters
sciencenewsroom@wiley.com
781-388-8408
Wiley

Researchers from Taiwan reveal that antiviral therapy for hepatitis C virus (HCV) improves kidney and cardiovascular outcomes for patients with diabetes. Results of the study published in Hepatology, a journal of the American Association for the Study of Liver Diseases, show that incidences of kidney disease, stroke, and heart attack were lower in patients treated with pegylated interferon and ribavirin compared to HCV patients not treated with antivirals or diabetic patients not infected with the virus.

The World Health Organization (WHO) estimates that diabetes affects 347 million individuals worldwide and another 170 million people are living with chronic HCV. Previous research suggests a link between diabetes and chronic HCV, with HCV infected individuals having a greater chance of developing insulin resistance and diabetes. Moreover, HCV patients with insulin resistance, with or without diabetes, have a poor response to antiviral treatment, increased progression of liver fibrosis and greater risk of developing liver cancer (hepatocellular carcinoma).

"There is growing evidence of an association between diabetes and HCV," explains lead author, Chun-Ying Wu, MD, PhD, MPH from Taichung Veterans General Hospital in Taiwan. "Our study investigates if antiviral therapy used to treat HCV infection also improves diabetes outcomes."

For this population-based study researchers used data from the Taiwan National Health Insurance Research Database, which has collected healthcare details for all residents of the country since 1997. The team indentified 1, 411 patients with diabetes and HCV who were enrolled in the study, and received pegylated interferon plus ribavirin. There were also 1,411 individuals in the untreated group and 5,644 patients with diabetes and without HCV in the uninfected cohort. Follow-up for all participants was from 2003 to 2011.

Findings indicate that the 8-year cumulative incidences of end-stage renal disease in the treated, untreated and uninfected groups were 1.1%, 9.3%, and 3.3%, respectively. Further analysis found stroke incidence was 3.1% for treated patients, 5.3% for untreated and 6.1 for uninfected subjects. Acute coronary syndrome—an umbrella term the American Heart Association uses to define diseases, such as heart attack or angina, where blood to the heart is blocked—occurred in 4.1%, 6.6% and 7.4% of treated, untreated and uninfected patients.

"Our findings suggest that HCV may cause clinical complications related to diabetes. But these issues are mitigated by HCV antiviral therapy, specifically pegylated interferon plus ribavirin, which was found to reduce risks of kidney disease, stroke and cardiovascular diseases in diabetic patients," concludes Dr. Wu. The authors recommend further examination of the underlying relationship between HCV and diabetes.

###

This study was funded in part by grants from Taiwan's National Health Research Institutes (PH-100-PP-54, PH-101-PP-23) and Taiwan's National Science Council (NSC 101-2314-B-650 -003).

This study is published in Hepatology. Media wishing to receive a PDF of the article may contact sciencenewsroom@wiley.com.

Full citation: "Antiviral Treatment for Hepatitis C Virus Infection is Associated with Improved Renal and Cardiovascular Outcomes in Diabetic Patients." Yao-Chun Hsu, Jaw-Town Lin, Hsiu J. Ho, Yu-Hsi Kao, Yen-Tsung Huang, Nai-Wan Hsiao, Ming-Shiang Wu, Yi-Ya Liu and Chun-Ying Wu. Hepatology; (DOI: 10.1002/hep.26892).

URL: http://doi.wiley.com/10.1002/hep.26892

Author Contact: Media wishing to speak with Dr. Wu may contact dr.wu.taiwan@gmail.com or at +866-921388866. Dr. Yao-Chun Hsu, the first author of this article, may be reached at +886-988687726.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on is published by Wiley on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://wileyonlinelibrary.com/journal/hep.

About Wiley

Wiley is a global provider of content-enabled solutions that improve outcomes in research, education, and professional practice. Our core businesses produce scientific, technical, medical, and scholarly journals, reference works, books, database services, and advertising; professional books, subscription products, certification and training services and online applications; and education content and services including integrated online teaching and learning resources for undergraduate and graduate students and lifelong learners.

Founded in 1807, John Wiley & Sons, Inc. (NYSE: JWa, JWb), has been a valued source of information and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Wiley and its acquired companies have published the works of more than 450 Nobel laureates in all categories: Literature, Economics, Physiology or Medicine, Physics, Chemistry, and Peace. Wiley's global headquarters are located in Hoboken, New Jersey, with operations in the U.S., Europe, Asia, Canada, and Australia. The Company's website can be accessed at http://www.wiley.com.

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Cardiovascular diseases and HCV infection: a simple association or more?

Gut doi:10.1136/gutjnl-2013-306102

Leading article

Salvatore Petta, Fabio Salvatore Macaluso, Antonio Craxì

+ Author Affiliations

Correspondence to
Dr S Petta, Gastroenterologia and Epatologia, Piazza delle Cliniche 2, Palermo 90127, Italy;
petsa@inwind.it

Received 17 September 2013
Revised 14 November 2013
Accepted 17 November 2013
Published Online First 2 December 2013

Introduction

HCV infection, metabolic disorders and cardiovascular alterations, considered alone or in combination, are common conditions in a large proportion of the general population. Consequently, determining whether the association of HCV infection with cardiometabolic disorders is simply coincidental or, conversely, caused by pathogenetic mechanisms (in)directly linking chronic HCV infection to these disorders, would be of extreme relevance.

Several clinical studies have shown that metabolic disorders—namely, type 2 diabetes,1insulin resistance (IR)2 and hepatic steatosis3—are highly prevalent in patients with chronic hepatitis C (CHC) compared with non-infected patients. Experimental and clinical studies have shown that HCV is able to directly influence glucose and lipid metabolism and thus can perturb the metabolic homeostasis of the host, leading to extrahepatic consequences.4 ,5 However, unlike the classic forms of metabolic disturbances, CHC is associated with a favourable lipoprotein profile—that is, reduced levels of apolipoprotein B containing lipoproteins, such as low density lipoprotein and very low density lipoprotein cholesterol.6

The discordance between the increased prevalence of IR, steatosis and diabetes, and the favourable lipoprotein profile in CHC compared with non-infected individuals, may account for the similar prevalence of metabolic syndrome (ie, the presence of at least three of the following: visceral obesity, hyperglycaemia, arterial hypertension, low levels of high density lipoprotein cholesterol and high triglycerides levels)7 reported in data from the database of the third National Health and Nutrition Examination Survey (NHANES-III).8

These data raise the question of whether HCV infection per se and/or via induction of metabolic/inflammatory dysfunctions is associated with an increased cardiovascular risk.

With this in mind, cross sectional and prospective studies have evaluated the presence and occurrence of both cardiovascular alterations and cardiovascular mortality in HCV infected patients compared with non-infected patients, with contrasting results.6 ,9–34

This review was prompted by …

Full text of this article

Clear Link Between Liver Disease and Risk for Cardiovascular Disease, Finds Saint Luke's Study

Assessment of 377 asymptomatic patients reveals non-alcoholic fatty liver disease (NAFLD) proves to be a stronger indicator than age, smoking, gender, or other traditional risk factors

KANSAS CITY, Mo., Oct. 16, 2013 /PRNewswire-USNewswire/ -- Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and other Western countries, affecting up to a third of the general population, and in most cases causing no signs or symptoms. NAFLD is the most common cause for cirrhosis and a common cause for primary liver cancer. Most affected individuals are completely unaware of their liver disease.

Now Saint Luke's liver specialists and cardiologists have discovered a compelling association between NAFLD and a high risk for cardiovascular disease. The link between the two was stronger than other more traditional risk factors for coronary artery disease such as smoking, hypertension, male gender, diabetes, high cholesterol, or metabolic syndrome. The research findings are published in an online article in the Mayo Clinic Proceedings posted Oct. 16, 2013.

The research study was a collaborative partnership between Saint Luke's Liver Disease Management Center gastroenterologists Rajiv Chhabra, M.D., and John Helzberg, M.D., and Saint Luke's Mid America Heart Institute cardiologists James O'Keefe, M.D., and Randall Thompson, M.D.

The study assessed upper abdominal CT images from 377 non-symptomatic patients undergoing non-contrast CT scans to determine coronary calcium scores. Using expanded imaging "windows" to include the liver and spleen, researchers found that patients with fatty liver disease were more likely to also have coronary artery disease. The research is compelling enough that cardiologists at Saint Luke's are considering changing their practices to include liver and spleen images in CT scans as a screening indicator of coronary artery disease risk.

Non-alcoholic fatty liver disease is the accumulation of fat in the liver in people who drink little to no alcohol. The fat can cause inflammation and scarring in the liver. Its most serious form can progress to cirrhosis, liver failure, or liver cancer. It is the most common liver disorder in Western countries and one of the fastest growing concerns among clinicians due to an escalating patient population with obesity and diabetes. 

"If current trends continue, the prevalence of NAFLD is expected to increase to 40 percent of the population by 2020," said Dr. Helzberg. "This discovery is important in identifying potential cardiovascular disease in NAFLD patients. Hopefully future research will yield better treatment options and disease management."  Treatments now primarily include lifestyle changes such as diet, exercise, and increased monitoring.

While more research is needed to explore the relationship between the two conditions, the growing number of patients with NAFLD suggests a potential role for increased screening among the medical community. "These findings suggest that patients with coronary artery disease should possibly be screened for liver disease. Likewise, NAFLD patients should be evaluated for coronary artery disease," said Dr. Chhabra.

Funding was provided through a research grant to Dr. Helzberg from the Saint Luke's Foundation and the Mid America Heart Institute Foundation.

"This study is another example of what can arise from cross-disciplinary collaboration that is increasingly common at Saint Luke's. By pooling our knowledge and insights, we are able to identify promising areas for research that may have a powerful impact on our ability to practice medicine and to improve the lives of our patients," said David J. Cohen, M.D., M.Sc., director of Cardiovascular Research at Saint Luke's Hospital.  

About Saint Luke's Liver Disease Management Center
At Saint Luke's Liver Disease Management Center, patients throughout the Midwest and across the United States have access to liver disease treatment options provided by a multidisciplinary physician group. From preventive care to liver transplantation, Saint Luke's provides a full range of services for patients with disorders of the liver, bile ducts, and pancreas.

About Saint Luke's Mid America Heart Institute
Saint Luke's Mid America Heart Institute, a member of Saint Luke's Health System and a teaching affiliate of the University of Missouri-Kansas City, is one of the preeminent cardiovascular programs in the country. Its legacy of innovation began more than 25 years ago when it opened as the nation's first heart hospital. Since then, the Heart Institute has earned a world-wide reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, women's heart disease, electrophysiology, outcomes research, and health economics.  With more than 50 full-time board certified cardiovascular specialists on staff, the Heart Institute offers one of the largest heart failure/heart transplant programs in the country, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches to opening challenging blocked arteries using minimally invasive techniques.

SOURCE Saint Luke's Hospital of Kansas City

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Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original

Yao-Chun Hsu^1,2, Jaw-Town Lin^2,3,4, Hsiu J. Ho³, Yu-Hsi Kao⁵, Yen-Tsung Huang⁶, Nai-Wan Hsiao⁷, Ming-Shiang Wu⁸, Yi-Ya Liu⁹, Chun-Ying Wu^{1,9,10,11,12,*}

DOI: 10.1002/hep.26892

Copyright © 2013 American Association for the Study of Liver Diseases

Publication History
Accepted manuscript online: 12 OCT 2013 09:51AM EST
Manuscript Accepted: 7 OCT 2013
Manuscript Revised: 23 SEP 2013
Manuscript Received: 25 MAY 2013

Keywords: hepatitis C virus; diabetes mellitus; antiviral therapy; Taiwan National Health Insurance Research Database

Abstract

Hepatitis C virus (HCV) infection is causally associated with insulin resistance and diabetes mellitus. This population-based cohort study aimed to investigate whether antiviral therapy for HCV infection was associated with improved clinical outcomes related to diabetes. From the Taiwan National Health Insurance Research Database, 2,267,270 Taiwanese residents diagnosed with diabetes mellitus were screened for eligibility. HCV infection was defined by a specific diagnosis code and measurement of serum antibody. After excluding patients with serious comorbidity, we enrolled a total of 1,411 eligible patients who received pegylated interferon plus ribavirin (treated cohort), and matched them 1:1 with 1,411 untreated controls by propensity scores (untreated cohort). We also matched the treated cohort 1:4 with 5,644 diabetic patients without HCV infection (uninfected cohort). Participants were followed up for the occurrence of end-stage renal disease (ESRD), ischemic stroke, and acute coronary syndrome (ACS) after receiving antiviral treatment or the corresponding calendar date. From 2003 to 2011, the 8-year cumulative incidences of ESRD in the treated, untreated, and uninfected cohorts were 1.1% (95% confidence interval [CI], 0.3-2.0%), 9.3% (95% CI, 5.9-12.7%), and 3.3% (95% CI, 2.3-4.3%), respectively (p<0.001); those of stroke were 3.1% (95% CI, 1.1-5.0%), 5.3% (95% CI, 3.0-7.5%), and 6.1% (95% CI, 4.8-7.4%), respectively (p=0.01); and those for ACS were 4.1% (95% CI, 2.1-6.1%), 6.6% (95% CI, 3.7-9.5%), and 7.4% (95% CI, 5.9-9.0%), respectively (p=0.05). As compared with the untreated cohort, antiviral treatment was associated with multivariate-adjusted hazard ratios of 0.16 (95% CI, 0.07-0.33%) for ESRD, 0.53 (95% CI, 0.30-0.93) for ischemic stroke, and 0.64 (95% CI, 0.39-1.06) for ACS, respectively. Conclusions: Antiviral treatment for HCV infection is associated with improved renal and cardiovascular outcomes in diabetic patients. (Hepatology 2013;)

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Infection, CVD more prevalent among liver transplant recipients with metabolic syndrome

Provided by Healio

June 3, 2013

ORLANDO, Fla. — The presence of metabolic syndrome post-liver transplantation increased the risk for infection and cardiovascular disease, according to data presented at Digestive Disease Week.

In a retrospective cohort study, researchers evaluated 158 patients who underwent liver transplantation between 2002 and 2007 at a single medical facility, with follow-up through September 2012. The presence of metabolic syndrome (MetS) before transplant and at 6 and 12 months post-transplant was determined in each case.

Before transplantation, 25% of the cohort had MetS, which increased at 6 months (51% of cases) and 12 months post-transplant (61%). Thirty-one percent of participants who did not have prior MetS developed it de novo at 6 months, while 54% developed it by 12 months.

Investigators observed a significant association between MetS at 6 months and infection-related hospitalizations within the first post-transplant year (53% of those with compared with 31% of those without MetS; P=.005). Hospitalizations due to cardiovascular disease (CVD) also were more common among those with post-transplant MetS (26% of cases at 5 years post-transplant vs. 13%; P=.05).

Patients with MetS and nonalcoholic fatty liver disease (NAFLD) were not at increased risk for either infection- or cardiovascular-related hospitalization compared with those with MetS alone. NAFLD, however, significantly increased the risk for CVD among patients without MetS (14% vs. 0% of those without NAFLD; P=.03). Neither MetS nor NAFLD significantly impacted post-transplant survival, according to Kaplan-Meier analysis.

“We were able to show there was a statistically significant association with early infectious morbidity, as well as later cardiovascular morbidity, if you have symptoms of [MetS],” researcher Nicholas Kim, MD, an internal medicine resident at the University of Wisconsin, told Healio.com. “Our data suggest that it’s important to prevent metabolic syndrome from developing post-liver transplant. It’s a very common complication due to a variety of reasons, but if we are able to prevent it, we might be able to reduce the amount of early infectious complications and later cardiovascular complications after liver transplant.”

For more information:

Kim N. Tu1019: Development of the Metabolic Syndrome and Its Outcomes After Liver Transplantation. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

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Fatty liver disease associated with cardiovascular risk in patients with HIV

Michael Carter
Published: 24 January 2011

Hardening of the arteries is common in HIV-positive patients, and is associated with fatty liver disease, US investigators report in the online edition of HIV Medicine.

“HIV-infected persons with fatty liver disease may warrant early cardiovascular assessment and institution of risk reduction methods,” comment the researchers.

Cardiovascular disease is an increasingly important cause of illness and death in patients with HIV. Studies conducted in HIV-negative individuals have shown that the presence of a fatty liver is associated with hardening of the coronary artery (atherosclerosis), an important risk factor for heart disease.

A team of investigators lead by Dr Nancy Crum-Cianflone wished to see if this was also the case for HIV-infected individuals.

They write: “Given that liver test abnormalities and fatty liver disease are common in among HIV infected persons, determining their relationship with coronary artery atherosclerosis may be helpful in the development of screening guidelines and risk stratification for underlying cardiovascular risk in this population.”

Between 2008 and 2010 they undertook a cross sectional study involving 223 HIV-positive adults. All the patients had a CT scan which checked for hardening, or calcification, of the coronary artery and fatty liver disease.

Atherosclerosis in the coronary artery was diagnosed if any calcification was detected (a score above 0), and a score above 100 was considered clinicially significant. Fatty liver was defined as a liver-to-spleen ratio < 0.1.

Information was also gathered on the patients’ demographics, CD4 cell count and viral load, use of antiretroviral drugs, lipid levels, and medical histories. A series of statistical analyses were then performed to see which factors were associated with hardening of the coronary artery.

With a median age of 43 years (range 36-50), the patients were relatively young. Risk factors for cardiovascular disease were common, and 39% had hypertension and 6% diabetes. Fatty liver can be a complication of viral hepatitis, but only 3% of the study population were co-infected with hepatitis C.

Most patients (83%) were taking antiretroviral therapy, 70% had an undetectable viral load and median CD4 cell count was 586 cells/mm3.

CT scanning showed that 34% of individuals had some hardening of the coronary artery, and that this was clinically significant for 8% of patients. Fatty liver was diagnosed in 13% of individuals.

Prevalence of fatty liver for patients with no evidence of hardening of the coronary artery was 8%. But this increased to 18% for individuals with a calcification score between 1-100, and was 41% for patients with clinically significant arterial hardening.

Overall, 59% of patients with fatty liver also had coronary atherosclerosis, and the correlation between the two conditions was significant (p = 0.02).

Statistical analysis that controlled for potentially confounding factors showed that three factors were significantly associated with calcification of the coronary artery: older age (each ten year increase, p < 0.01); fatty liver disease (p < 0.01), and hypertension (p < 0.01).

The relationship between hardening of the coronary artery and fatty liver disease was extremely robust, and was unaltered when the investigators excluded the small number of patients with hepatitis C, or those with metabolic syndrome. It was also present when patients with alcohol use were excluded from analysis.

“In our study, HIV-infected persons, despite their relatively young age, had a high prevalence of subclinical heart disease,” write the authors. They believe rheir results “emphasize the importance of cardiovascular disease among HIV-infected patients and suggest that addressing underlying heart disease may be an important component of further normalizing the life expectancy of this group.”

Inflammation could, the authors believe, be causing both the hardening of the arteries and the fatty liver disease observed in their patients.

Dr Crum-Cianflone and her colleagues conclude: “Fatty liver disease is associated with underlying cardiovascular disease and should be considered as a novel marker for risk stratification among HIV-infected persons.”

Reference

Crum-Cianflone N et al. Fatty liver disease is associated with underlying cardiovascular disease in HIV-infected persons. HIV Med, online edition (DOI: 10.1111/j.1468-1293.2010.00904.x), 2011 (click here for the free abstract).

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