Hyperoxia: Effective Mechanism of Hyperbaric Treatment at Mild-Pressure.

HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future.

Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention.

UNLABELLED: Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).

Arterial blood pressure is closely related to ascites development in compensated HCV-related cirrhosis.

BACKGROUND: Arterial blood pressure (BP) is a reliable marker of circulatory dysfunction in cirrhotic patients. There are no prospective studies evaluating the association between different levels of arterial BP and ascites development in compensated cirrhotic patients. Therefore, we evaluated the relationship between arterial BP and ascites development in compensated cirrhotic patients. MATERIALS AND METHODS: A total of 402 patients with compensated HCV-related cirrhosis were prospectively followed during 6 years to identify ascites development. At baseline, patients underwent systolic, diastolic and mean arterial pressure (MAP) measurements. Any history of arterial hypertension was also recorded. The occurrence of events such as bleeding, hepatocellular carcinoma, death and liver transplantation prior to ascites development were considered as competing risk events. RESULTS: Over a median of 156 weeks, ascites occurred in 54 patients (13%). At baseline, MAP was significantly lower in patients with ascites development (75.9 mm/Hg [95%CI, 70.3-84.3]) than those without ascites (93.6 mm/Hg [95% CI: 86.6-102.3]). After adjusting for covariates, the 6-year cumulative incidence of ascites was 40% (95%CI, 34%-48%) for patients with MAP<83.32 mm/Hg. In contrast, cumulative incidences of ascites were almost similar among patients with MAP values between 83.32 mm/Hg and 93.32 mm/Hg (7% [95% CI: 4%-12%]), between 93.32 mm/Hg and 100.31 mm/Hg (5% [95% CI: 4%-11%]) or higher than 100.31 mm/Hg (3% [95% CI: 1%-6%]). The MAP was an independent predictor of ascites development. CONCLUSIONS: The MAP is closely related to the development of ascites in compensated HCV-related cirrhosis. The risk of ascites development increases in 4.4 fold for subjects with MAP values <83.32 mm/Hg.

Viusid, a nutritional supplement, increases survival and reduces disease progression in HCV-related decompensated cirrhosis: a randomised and controlled trial.

OBJECTIVES: Viusid is a nutritional supplement with recognised antioxidant and immunomodulatory properties which could have beneficial effects on cirrhosis-related clinical outcomes such as survival, disease progression and development of hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of viusid in patients with HCV-related decompensated cirrhosis. DESIGN: A randomised double-blind and placebo-controlled study was conducted in a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). The authors randomly assigned 100 patients with HCV-related decompensated cirrhosis to receive viusid (three oral sachets daily, n=50) or placebo (n=50) during 96 weeks. The primary outcome of the study was overall survival at 96 weeks, and the secondary outcomes included time to disease progression, time to HCC diagnosis, time to worsening of the prognostic scoring systems Child-Pugh and Model for End-Stage Liver Disease, and time to a new occurrence or relapse for each one of the main clinical complications secondary to portal hypertension at 96 weeks. RESULTS: Viusid led to a significant improvement in overall survival (90%) versus placebo (74%) (HR 0.27, 95% CI 0.08 to 0.92; p=0.036). A similar improvement in disease progression was seen in viusid-treated patients (28%), compared with placebo-treated patients (48%) (HR 0.47, 95% CI 0.22 to 0.89; p=0.044). However, the beneficial effects of viusid were wholly observed among patients with Child-Pugh classes B or C, but not among patients with Child-Pugh class A. The cumulative incidence of HCC was significantly reduced in patients treated with viusid (2%) as compared with placebo (12%) (HR 0.15, 95% CI 0.019 to 0.90; p=0.046). Viusid was well tolerated. CONCLUSIONS: The results indicate that treatment with viusid leads to a notable improvement in overall clinical outcomes such as survival, disease progression and development of HCC in patients with HCV-related decompensated cirrhosis. Trial registration number http://ClinicalTrials.gov (NCT00502086).