Sex is a central aspect of human life and is significantly impacted by chronic illness. Cirrhosis, due to its unique pathophysiology and the side effects of common therapies, serves as a paradigmatic example, being associated with very high rates of sexual dysfunction in both men and women. Liver transplantation can modify certain hormonal and pathophysiological aspects related to sexual dysfunction, but complete recovery occurs in only a relatively small percentage of patients. This review examines the pathophysiology, epidemiology, and management of sexual and reproductive dysfunction in patients with cirrhosis and those undergoing liver transplantation. It provides a framework for understanding the sources of dysfunction, tools for identifying it in clinical settings, and interventions to improve sexual health and functioning in these patients.

Depressive and anxiety symptoms are more prevalent in patients with cirrhosis compared to the general population. Between 2009 and 2019, the prevalence of depression in cirrhosis increased by 80%, while the prevalence of generalized anxiety disorder increased by over 400%. When present, anxiety and depression are linked to lower health-related quality of life, more severe symptoms (eg, fatigue), and poorer response to medical treatment. Screening instruments for depression and anxiety have shown acceptable validity in patients with cirrhosis. However, the diagnosis of depression and anxiety disorder remains challenging in this population and should follow the established criteria for general populations. Treatment interventions are numerous and include patient education and support around liver disease, pharmacological agents, and psychotherapy. Antidepressants are the treatment of choice for patients with depressive or anxiety disorder and cirrhosis. However, consideration must be given to dose adjustment and choice of agent due to changes in their metabolism in patients with liver disease. Psychotherapy may be used as a stand-alone therapy or concomitantly with pharmacotherapy. The high prevalence and complexity of depressive and anxiety symptoms in patients with cirrhosis support the integrated care approach in which patients are cared for by multidisciplinary teams.

Phosphodiesterase 5 (PDE5) inhibitors presented themselves as important players in the nitric oxide/cGMP pathway, thus exerting a profound impact on various physiological and pathological processes. Beyond their well-known efficacy in treating male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), a plethora of studies have unveiled their significance in the treatment of a myriad of other diseases, including cognitive functions, heart failure, multiple drug resistance in cancer therapy, immune diseases, systemic sclerosis and others. This comprehensive review aims to provide an updated assessment of the crucial role played by PDE5 inhibitors (PDE5-Is) as disease-modifying agents taking their limiting side effects into consideration. From a medicinal chemistry and drug discovery perspective, the published PDE5-Is over the last 10 years and their binding characteristics are systemically discussed, and advancement in properties is exposed. A persistent challenge encountered with these agents lies in their limited isozyme selectivity; considering this obstacle, this review also highlights the breakthrough development of the recently reported PDE5 allosteric inhibitors, which exhibit an unparalleled level of selectivity that was rarely achievable by competitive inhibitors. The implications and potential impact of these novel allosteric inhibitors are meticulously explored. Additionally, the concept of multi-targeted ligands is critically evaluated in relation to PDE5-Is by inspecting the broader spectrum of their molecular interactions and effects. The objective of this review is to provide insight into the design of potent, selective PDE5-Is and an overview of their biological function, limitations, challenges, therapeutic potentials, undergoing clinical trials, future prospects and emerging uses, thus guiding upcoming endeavors in both academia and industry within this domain.

Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people.

The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective β-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men.

Approximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

End-stage liver disease (ESLD) is the culmination of progression of chronic liver disease to cirrhosis, decompensation, and chronic liver failure, featuring portal hypertension or hepatocellular failure-related complications. Liver transplantation offers improved long-term survival for these patients but is negatively influenced by donor availability, financial constraints in developing countries, active substance abuse, progression of disease or malignancy on wait-list, sepsis and extrahepatic organ involvement. In this context, palliative care (PC), an interdisciplinary medical practice that aim to prevent and relieve suffering, offers best possible quality of life and is not limited to end-of-life care. It also encompasses achievable goals such as symptom control and aggressive disease-modifying treatments or interventions that beneficially alter the natural course of the disease to offer curative intend. In this narrative review, we discuss the prognostic factors that define disease course in ESLD, various indications and challenges in PC for advanced cirrhosis and management options for major symptom burden in patients with ESLD based on evidence-based best practice.

This study aimed to review recent evidence on conservative non-surgical options for erectile dysfunction (ED) in men. A narrative review of the literature was performed. A comprehensive search in the MEDLINE, Embase, and Cochrane databases was done. Papers in English language, published from May 2017 until May 2022, were included. Papers reporting basic research or animal research were excluded, as long as reviews or meta-analyses. Congress reports, clinical cases, or clinical trials protocols with no results were also excluded.

We found a multitude of different treatment modalities for ED. We must take into account the type of patient, their comorbidities, the origin of their ED, and its severity in order to reproduce effective results using these therapies. Some of the treatments show good results with a good level of evidence (new IPDE5 formulations, intracavernous injections, shock wave therapy, hormonal theraphy, psycho-sexual theraphy). However, others (some new molecules, stem cell theraphy, platelet-rich plasma injections, oxygenation-based therapy, nutraceuticals), although some of them present promising results, require randomized studies with a larger number of patients and a longer follow-up time to be able to establish firm recommendations. Regarding the conservative treatment of erectile dysfunction, in recent years, some therapies have been consolidated as effective and safe for certain types of patients. On the other hand, other treatment modalities, although promising, still lack the evidence and the necessary follow-up to be recommended in daily practice.

Erectile dysfunction (ED) is common in men with cirrhosis. The aim of this study was to assess the prevalence of ED and the factors associated with ED in men with cirrhosis.

400 men with cirrhosis [Child-Turcotte-Pugh (CTP) class A, 44.0%; CTP class B, 41.0%; and CTP class C, 15.0%] having high Karnofsky performance score, and living in a stable monogamous relationship with a female partner were included in the study. International Index of Erectile Function (IIEF) questionnaire, and Short-Form (36) Health Survey (SF-36) were used to assess erectile function and the health-related quality of life (HRQOL), respectively.

ED was found in 289 (72.3%) patients. Patients with ED reported significantly lower SF-36 scores across all the eight domains of SF-36 (i.e., physical functioning score, role physical score, bodily pain score, general health perception score, vitality score, social functioning score, role emotional score, and mental health score); physical component summary score, and mental physical component summary score, compared with those without ED. On multivariate analysis, factors associated with ED were older age, longer duration of cirrhosis, CTP-C (vs. CTP-A), higher hepatic venous pressure gradient (HVPG), presence of generalized anxiety disorder (GAD), presence of major depression, and lower appendicular skeletal muscle index measured by dual-energy X-ray absorptiometry (DEXA ASMI).

ED is common in men with cirrhosis, and men with ED have poor HRQOL compared with those without ED. Older age, longer duration of cirrhosis, CTP-C (vs. CTP-A), higher HVPG, presence of GAD, presence of major depression, and lower DEXA ASMI are associated with ED.

Sexual dysfunction (SD) is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis. The etiology of SD is multifactorial and therefore treatment strategies are complex, especially in females. Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females, no single drug is available for SD, therefore multimodal treatment is required depending upon the cause. The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases. Improved quality of life is helpful in improving SD and vice versa is also true. Therefore, patients suffering from liver diseases should come forward and ask for treatment for SD, and physicians should actively enquire about SD while history taking and evaluating these patients. SD results in deterioration of quality of life, and both are modifiable and treatable aspects of liver diseases, which are never addressed actively, due to social taboos and fears of SD treatment in the presence of liver diseases. The diagnosis of SD does not require costly investigations, as the diagnosis can be established based on validated questionnaires available for both genders, therefore detailed targeted history taking using questionnaires is essential. Data are emerging in this area but is still at an early stage. More studies should be dedicated to SD in liver diseases.

Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes.

We conducted a narrative review of the literature focusing on the most recent advances.

We review the aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, and the current landscape of clinical trials for non-alcoholic steatohepatitis. We review the current standard of care and latest developments in the management of hepatic encephalopathy (HE), ascites and hepatorenal syndrome. We evaluate the promise and drawbacks of chemopreventative therapies that have been examined in trials and observational studies which may reduce the risk of hepatocellular carcinoma and cirrhosis complications. Finally, we examine the therapies which address the non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue.

The improvement of clinical and patient-reported outcomes for patients with cirrhosis is possible by applying evidence-based pharmacotherapeutic approaches to the prevention and treatment of cirrhosis complications.