Sexual Dysfunction in Patients With Cirrhosis Before and After Liver Transplantation

PREVALENCE OF ERECTILE DYSFUNCTION IN PATIENTS WITH CIRRHOSIS BEFORE AND AFTER LIVER TRANSPLANTATION. EFFECTIVENESS OF PHOSPHODIESTERASE-5 INHIBITORS.

1. Research objectives The aims of investigators study are: (1) to compare the prevalence of erectile dysfunction (ED) in a population of patients with cirrhosis before liver transplantation (LT) and one year after LT; (2) to describe factors associated with ED before and after LT, with a special focus of hormonal profile, neurocognitive impairment, multimodal brain Magnetic resonance imaging (MRI) and of the type of immunosuppressive therapy used; (3) to assess the impact of ED on sexual partner; (4) to evaluate the efficacy of the treatment with phosphodiesterase-5 inhibitors (PDE-5) drugs before and after LT.
2. Scientific context (international + any preliminary results of the teams involved) Erectile dysfunction (ED) is defined as the inability to develop or maintain an erection during sexual intercourse (1, 2) and is the main concern in terms of sexual dysfunction among men. The prevalence of ED increases with age, ranging from 9.1% in men 40-49 years to 54.9% in men >70 years (3). The major risk factors for ED are as follows: diabetes; heart conditions; tobacco use; obesity; injuries to the nerves that control erection; medications such as antidepressants; psychological conditions such as stress, anxiety, or depression; and drug or alcohol use (4). The International Index of Erectile Function (IIEF5) is a simple and well-validated tool for the evaluation of ED (5) and is considered the gold standard for the diagnosis and evaluation of symptom severity. The link between liver diseases, especially cirrhosis, and ED has not been well established. Chronic liver disease, especially cirrhosis, may also be associated with an increased risk of ED (6,7). Hormonal abnormalities, such as hyperoestrogenism, are well-known consequences of liver failure. Data regarding the prevalence of ED are inhomogeneous, with reports varying from 63% to 93% (8, 9) in patients who are candidates for liver transplantation (LT). The largest study published to date in patients with cirrhosis (7) showed that ED in cirrhotic patients is impacted by liver function, portal hypertension and known risk factors, such as diabetes mellitus and arterial hypertension. More recently, a second study conducted in 102 patients with Child-Pugh A cirrhosis suggested that cirrhosis was not a risk factor for ED per se (10). Investigators recently conducted an observational monocentric study in patients with cirrhosis (manuscript under revision). Investigators confirmed that ED was very frequent in their population (85%). Investigators also found that the severity of liver disease, assessed by the MELD or Child-Pugh score, was an independent factor associated with ED. Moreover, investigators found a very strong correlation between neurocognitive performance, evaluated by the psychometric hepatic encephalopathy test score (PHES), and ED. Last, investigators observed that in the subgroup of patients with compensated cirrhosis, ED was significantly more frequent in patients with MHE than in patients without MHE. A recent brain MRI study has suggested that cortical volume and white matter microstructural changes were observed in patients with ED and showed significant correlations with clinical symptoms (11). The modifications of those features after treatment by PDE-5 have never been described. Data regarding the prevalence of ED after liver transplantation (LT) are heterogeneous and scarce. Two studies conducted in China (8, 9) have shown slight improvements in ED after LT. However, the results were obtained from a small cohort of patients, and the authors insisted on an association between post-LT ED and immunosuppressive therapy, which is an obvious confounding factor. In kidney transplantation, a recent meta-analysis has suggested that phosphodiesterase inhibitor drugs are efficient in ≈60%.
3. Implementation date and duration Investigators plan to implement the study in July 2019. Investigators aim to evaluate 100 patients before and one year after LT. As 110 LT are performed each year in investigator's centre (75% male gender), the study is going to last 2 years and a half.
4. Protocol

• Type of study

This is a prospective study that will be performed in La Pitié-Salpêtrière Hospital. For the purpose of this study, patients will be admitted in the investigator's team day hospital structure, where investigators routinely perform neurological and neuropsychological work-up of patients before LT, including neuropsychological assessment, biological sampling, multimodal MRI. This structure is completely automatized and requires nurses, a neuropsychologist, neurologists, and hepatologists in order to diagnose neurological disorders in hepatological situations. Patients' relatives also fill up questionnaires. All caregivers involved in patient's evaluation build a clinical conclusion at the end of the day hospital and give a detailed record to the patient.

• Population