Living Liver Donors Report Lower Sexual Function in Early Months Post-Surgery

Donor Education Pre-Transplant May Help Improve Recovery, Reduce Concerns

A new study found that sexual function in adult living donors was lower at the evaluation phase and at three months following liver transplantation. Results published in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, suggest that donor education prior to surgery may improve recovery and ease concerns about sexual function following the transplant.

Living liver donors provide a healthy portion of their liver to an individual with end-stage liver disease. These donors make a personal sacrifice to help save another individual from certain death. Much of the medical literature focuses on the health-related quality of life of donors, but limited evidence is available regarding sexual function. A prior single-center study found that nearly 50% of donors reported a worsening of sexual function one week to one month following donation, returning to normal at three months post-operation.

“To further knowledge in this important area, our study sought to identify the extent of sexual concerns for liver donors,” said lead author Dr. Andrea DiMartini with Western Psychiatric Institute and Clinic in Pittsburgh, Pa. “Our investigation examined sexual functioning of liver donors before and after donation using data from a multi-site investigation, known as the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

For this study the team examined the sexual function of 208 liver donors and any changes that may occur during the first year following donation using self-reported surveys. A group of 155 non-donors also completed the survey that included questions regarding sexual desire, satisfaction, orgasm, and erectile function in men.

Analyses show that donor sexual performance was lower at the time of evaluation and three months after transplant surgery than at one year following donation. Researchers found that during the early recovery phase, abdominal pain was linked to difficulty reaching orgasm; concerns over appearance was associated with lower sexual desire; and not feeling back to normal correlated to a dissatisfaction with sexual life.

Dr. DiMartini concludes, “The goal of all donor teams is to create a positive experience, both mentally and physically, and reduce stress for organ donors. Our findings suggest that providing more information to donors about what to expect with sexual function will help ease concerns and prepare themselves for the early days following liver transplant surgery.”

This study was funded in part by the National Institute of Diabetes & Digestive & Kidney Diseases (grants U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK085587, U01-DK85515, and U01-DK62536), the Health Resources and Services Administration (HRSA), and the American Society of Transplant Surgeons (ASTS).

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Full citation: “Patterns and Predictors of Sexual Function after Liver Donation: the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL).” AF DiMartini, MA Dew, Z Butt, MA Simpson, DP Ladner, AR Smith, P Hill-Callahan and BW Gillespie. Liver Transplantation; (DOI: 10.1002/lt.24108).

URL: http://doi.wiley.com/10.1022/lt.24108
Author Contact: Media wishing to speak with Dr. DiMartini may contact Jenya Abramovich with Arbor Research at jenya.abramovich@arborresearch.org.

About the Journal
Liver Transplantation is published by Wiley on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AASLD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit http://wileyonlinelibrary.com/journal/lt.

About Wiley
Wiley is a global provider of knowledge and knowledge-enabled services that improve outcomes in areas of research, professional practice and education. Through the Research segment, the Company provides digital and print scientific, technical, medical, and scholarly journals, reference works, books, database services, and advertising. The Professional Development segment provides digital and print books, online assessment and training services, and test prep and certification. In Education, Wiley provides education solutions including online program management services for higher education institutions and course management tools for instructors and students, as well as print and digital content.

EASL 2015: Alcohol use disorders – stronger predictor of mortality than chronic hepatitis C virus infection

Chronic hepatitis C infection is associated with increased risk of mortality when severe comorbidities and/or alcohol use disorders are also present

April 25, 2015, Vienna, Austria: Results presented today at The International Liver Congress™ 2015, show that alcohol use disorders (AUD) have a serious, negative prognostic outcome with higher mortality risks in the general population and patients with hepatitis C virus (HCV) infection in particular.

The study found that chronic HCV infection has a limited impact on mortality, unless the patient also has other severe comorbidities, such as HIV infection, cancer or chronic kidney disease. In contrast, those with AUDs are at significant risk of death with a higher mortality risk observed across all the study subgroups.

Michaël Schwarzinger, Director, THEN (Translational Health Economics Network) and Vincent Mallet, Professor of Hepatology, Université Paris Descartes and Assistance Publique – Hôpitaux de Paris, France, commented: "There is an epidemiological relationship between chronic HCV infection and AUD. However, the burden of chronic HCV infection analyses barely take into account the potential confounding role of AUD on prognosis. Our primary aim was to study the confounding role of severe comorbidities and AUD on prognosis in Hep C patients in a real-life setting."

Between 2008 and 2012, 28,953,755 adults residing in Metropolitan France were hospitalised and 1,506,453 died at hospital. All hospitalised patients were characterised by severe comorbidities and their trajectory was tracked according to chronic HCV infection and/or AUD. Chronic HCV infection was present in 112,146 (0.39%) of hospitalised patients, AUD in 705,259 (2.44%), and both chronic HCV infection and AUD in 23,351 (i.e., 20.8% AUD recorded in Hep C patients).

The researchers found that:

• Chronic HCV infection was mostly associated with higher mortality risks in the presence of severe comorbidities (e.g., HIV/AIDS, liver transplant receipt)
• In the absence of severe comorbidities, the prognostic value of chronic HCV infection was mostly explained by the presence of AUD (end-stage liver disease and mortality)
• More broadly, AUD was associated with higher mortality risks in all hospitalized patients, and alcohol withdrawal or abstinence was significantly associated with lower mortality risks

"These results show that alcohol use disorders are a much more accurate indicator of mortality in chronic HCV infection, and highlight the need to encourage alcohol withdrawal and abstinence in all patients," said Professor Tom Hemming Karlsen, Scientific Committee Member, European Association for the Study of the Liver.

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About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL
Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it 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.

Contact
For more information, please contact the ILC Press Office at:
ilc.press@easloffice.eu or
+44 (0)20 3580 5444

General session 3, Hall D Presentation time: 09:45-10:00 Presenter: Michaël Schwarzinger (France)

Abstract G16:THE COUNFOUNDING ROLE OF SEVERE COMORBIDITIES AND ALCOHOL USE DISORDERS ON PROGNOSIS IN CHRONIC HEPATITIS C VIRUS INFECTION: AN ANALYSIS OF THE 2008-2012 FRENCH NATIONAL HOSPITAL DISCHARGE DATABASE
Michaël Schwarzinger* 1, Sophie Thiébaut2, Vincent Mallet3, Jürgen Rehm4 1THEN (Translational Health Economics Network), Paris, Canada, 2THEN (Translational Health Economics Network), 3Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France, 4Social and Epidemiological Research (SER) Department, Centre for Addiction and Mental Health, Toronto, Canada

Background and Aims: There is an epidemiological relationship between chronic hepatitis C virus (HCV) infection and alcohol use disorders (AUD). AUD is a leading cause of liver disease and death. However, burden of chronic HCV infection analyses barely take into account the potential confounding role of AUD on prognosis. Our aim was to compare the prognostic value of chronic HCV infection and AUD in the general population.

Methods: In 2008-2012, 28,953,755 adult individuals residing in Metropolitan France were hospitalized and 1,506,453 died at hospital (51.6% and 55.7% of National Vital Statistics, respectively). We characterized all hospitalized patients by severe comorbidities (see Table), and tracked their trajectory according to chronic HCV infection and/or AUD (including withdrawal/abstinence). Age at death was analyzed in multivariate Cox proportional hazards model from January 2008 to last discharge or transplantation with stratification by gender, main French regions, and having received care in teaching hospitals.

Results: Chronic HCV infection was present in 112,146 (0.39%) of hospitalized patients, AUD in 705,259 (2.44%), both chronic HCV infection and AUD in 23,351(0.08%; i.e., 20.8% of HCV and 3.3% of AUD). Overall, the adjusted hazard ratio of in-hospital death (aHR) was 1.90 (95% confidence interval 1.86-1.94), for chronic HCV infection and 3.13 (3.10-3.15) for AUD, with a negative interaction effect between chronic HCV infection and AUD (aHR, 0.93; 0.90-0.97). Alcohol withdrawal or abstinence was significantly associated with lower mortality risks (HR, 0.66; 0.65-0.67). Subgroup analyses by severe comorbidities revealed that chronic HCV infection was only associated with higher mortality risks in presence of severe comorbidities (Table: groups 1 to 4, and 7 to 12). In absence of severe comorbidities, the prognostic value of chronic HCV infection at all liver disease stages was either not statistically significant among patients with cirrhosis and milder liver disease stage (groups 13 to 17). In contrast, AUD was associated with higher mortality risks in all prognostic subgroups, including all liver disease stages.

Conclusions: AUD has a dismal prognostic value in the general population and in the minority group of patients with chronic HCV infection. Alcohol withdrawal and abstinence increase survival regardless of HCV treatment.

Disclosure of Interest: None Declared

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Source:  http://www.eurekalert.org/pub_releases/2015-04/eaft-aud042415.php

EASL 2015: ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)

• 97% of post-transplant patients with HCV genotype 1a achieved cure
• 91% of post-transplant patients with HCV genotype 3 achieved cure  
• No need seen to alter existing transplantation medication regimens

Saturday, April 25, 2015 10:00 am EDT

(PRINCETON, N.J., APRIL 25, 2015) – Bristol-Myers Squibb Company (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50^th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.

“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine, Chief, Hepatology, University of Texas Health Science Center and VP, Academic and Clinical Affairs Texas Liver Institute. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”

The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).

The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.

Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.

In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.

 HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.

Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available here.)

Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs.

“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”

About ALLY-1: Study Design
This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.

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EASL 2015: Statin use in HCV patients may lower risk of death, decompensation

VIENNA — Statin use in patients with hepatitis C virus and compensated cirrhosis seems to offer a protective effect against death and decompensation, according to a study presented at the 2015 International Liver Congress.

 “In compensated HCV cirrhosis, statin users have a significantly lower incidence of decompensation and better overall survival compared to statin non-users,” Arpan Mohanty, MD, from Yale School of Medicine, New Haven, Conn., said during her presentation. “Risk of decompensation and death was reduced by over 40%.”

In this retrospective cohort study, Mohanty and colleagues used the U.S. Department of Veterans HCV Clinical Case Registry, and by doing so, she said all patients would have had an equal opportunity to receive statins. 

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EASL 2015: Use of direct-antiviral agents helps overcome hepatitis C recurrence in liver transplant patients

New data presented today at The International Liver Congress 2015, supports the use of sofosbuvir (SOF)- and daclatasvir (DCV)-based regimens in patients with recurrence of the hepatitis C virus (HCV) following liver transplantation (LT). The results are based on data from patients with HCV being treated with second-generation DAAs in the large French prospective ANRS CO23 CUPILT study. Among them, 296 patients were treated with a combination of SOF+DCV, with or without ribavirin.

SOF- and DCV-based regimens offered high rates of sustained virologic response (SVR) coupled with good tolerance. The presented results focus on 130 patients who achieved SVR12; end of treatment therapy and SVR12 rates are 98% and 96%, respectively.

"The use of interferon-free regimens using DAAs has dramatically improved the management of liver transplant patients infected with HCV. The outstanding efficacy and safety results that sofosbuvir- and daclatasvir-based regimens demonstrated in patients with recurrent hepatitis C are impressive and will help us identify optimal treatment strategies using these new therapies," said Audrey Coilly, MD, Paul Brousse Hospital, Villejuif.

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EASL 2015: Hepatitis C screening essential to help catch patients with advanced liver fibrosis

Research validates the current recommendation that screening for hepatitis C, particularly among high-risk groups, is vital.

April 25, 2015, Vienna, Austria: Study results presented today at The International Liver Congress™ 2015 show that the occurrence of advanced liver fibrosis is similar for patients infected with the hepatitis C virus (HCV), whether or not they have been diagnosed.

Most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. The study authors used the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed. They then compared liver fibrosis between respondents of the National Health and Nutrition Examination Survey (NHANES) in the USA, in patients with diagnosed and undiagnosed HCV infection.

Of the respondents with known HCV infection, the proportion with a high, intermediate and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively; in those with undiagnosed HCV the results were 19.1%, 30.9%, 50.0%, respectively.

The study highlights that even if people are unaware they are infected with HCV, the virus affects their liver in the same way, resulting in advanced fibrosis. These results validate the current recommendation that screening for HCV, particularly among high-risk groups, is vital.

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EASL 2015: Cancer rates among patients with hepatitis C are increased compared to those not infected

New results show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer. 

Results recently announced at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher.

The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.

A retrospective study at Kaiser Permanente, Southern California, USA, was conducted. The study authors recorded all cancer diagnoses in patients over 18 years of age with or without HCV during 2008-2012. Within the timeframe of the study 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non-HCV cohort.

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