Hepatopulmonary Syndrome and Liver Transplantation: A Recent Review of the Literature

A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal hypertension, intrapulmonary vascular dilatations, and increased alveolar-arterial oxygen gradient. Prevalence varies according to various study groups from 4%–47%. While the most common presenting symptom of HPS is dyspnea, it is usually asymptomatic, and thus all liver transplant candidates should be screened for its presence. Pulse oximetry is a useful screening method, but arterial blood gas examination is the gold standard. If there is an abnormal P (A-a)O₂ gradient, microbubble transthoracic echocardiography should be done for diagnosis. Outcome is unpredictable, and there is currently no effective medical therapy. The only effective therapy is considered to be liver transplantation. Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.     

Angiotensin receptor blocker use is associated with upregulation of the memory-protective angiotensin type 4 receptor (AT4R) in the postmortem brains of individuals without cognitive impairment

The reported primary dementia-protective benefits of angiotensin II type 1 receptor (AT₁R) blockers (ARB) are believed, at least in part, to arise from systemic effects on blood pressure. However, there is a specific and independently regulated brain renin-angiotensin system (RAS). Brain RAS acts mainly through three receptor subtypes; AT₁R, AT₂R, and AT₄R. The AT₁R promotes inflammation and mitochondrial reactive oxygen species generation. AT₂R increases nitric oxide. AT₄R is essential for dopamine and acetylcholine release. It is unknown whether ARB use is associated with changes in the brain RAS. Here, we compared the impact of treatment with ARB on not cognitively impaired individuals and individuals with Alzheimer’s dementia using postmortem frontal-cortex samples of age- and sex-matched participants (70–90 years old, n?=?30 in each group). We show that ARB use is associated with higher brain AT₄R, lower oxidative stress, and amyloid-β burden in NCI participants. In AD, ARB use was associated with lower brain AT₁R but had no impact on inflammation, oxidative stress, or amyloid-β burden. Our results may suggest a potential role for AT₄R in the salutary effects for ARB on the brains of not cognitively impaired older adults.

Graphical abstract