Both authors contributed equally to this work.The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002LT in -2007 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO 2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO 2 ) !20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; logrank, p ¼ 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p ¼ 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen. Hepatopulmonary syndrome (HPS) is characterized by blood oxygen changes that are caused by pulmonary vascular dilations in patients with liver disease (1,2). The criteria that are used to define HPS and the reported prevalence of HPS in patients with liver cirrhosis and in candidates for liver transplantation (LT) vary widely in the literature (4-32%) (3-7). The cause of HPS is unknown, and the association between liver dysfunction and portal hypertension remains controversial, as reported by different studies (4-10). Orthodeoxia is considered to be characteristic of HPS; however, the prevalence of this condition in patients with HPS is only 25% (1,11).The association between HPS and increased mortality in patients with cirrhosis who are candidates for LT has been disputed. A recent prospective multicenter study identified associations between HPS, independent of its severity, and increased mortality and poorer quality of life (7). Other studies of HPS and LT were retrospective (12) or were based on small sample sizes (6).LT is the treatment of choice for HPS. Early results of LT in patients with HPS have been disappointing and have
We evaluated baroreflexes in 58 diabetic and 15 control subjects by determining the latency of response between the end of a Valsalva maneuver (VM) and points on the resultant blood pressure and heart rate (HR) response curves. Prolonged latencies indicative of sympathetic dysfunction were demonstrated in 44% to 88% of diabetic subjects. The results challenge the view that sympathetic dysfunction cannot be detected before parasympathetic abnormalities are manifest. Baroreflex latencies reflected sympathetic dysfunction early in the course of diabetes, sometimes in patients with normal HR responses to deep breathing and to a VM.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second cause of cancer related death due to latent liver disease, late diagnosis and non-available therapeutic treatment. Liver biopsy is still the gold standard in order to know the molecular biology of the tumor, its behaviour and invasive characteristics. Conventional diagnosis methods for HCC detection include imaging and serological tests with low sensitivity and specificity. In this review, we focus on the potential utility of certain serum biomarkers and a new approach, "liquid biopsy", in the management of HCC patients.
Background and Aims
Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA‐H19 as a biomarker for liver cancer.
Methods
LncRNA‐H19 expression levels and the functional assays were conducted in EpCAM+CD133+ CSCs and C57BL/6J mice fed with a high‐fat high‐cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA‐H19 levels in an estimation and validation cohort.
Results
EpCAM+CD133+ cells showed a stem cell‐like phenotype, self‐renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA‐H19 (p < .001). Suppression of lncRNA‐H19 by antisense oligonucleotide treatment significantly reduced the self‐renewal capacity (p < .001). EpCAM, CD133 and lncRNA‐h19 expression increased accordingly with disease progression in HFHCC‐fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA‐H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA‐H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow‐up showed higher lncRNA‐H19 levels (p = .0025).
Conclusion
LncRNA‐H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow‐up showed higher levels of lncRNA‐H19. LncRNA‐H19 could constitute a new biomarker of HCC.
Obtaining blood gas measurements in the supine position and the use of modern criteria are more sensitive for the diagnosis of HPS. Blood gas analysis with the patient seated detects a greater number of severe and very severe cases. The presence of HPS was not associated with an increase in mortality regardless of blood gas criterion used.
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