Update in the Treatment of the Complications of Cirrhosis.

Cirrhosis consists of 2 main stages: compensated and decompensated, the latter defined by the development/presence of ascites, variceal hemorrhage, and hepatic encephalopathy. The survival rate is entirely different, depending on the stage. Treatment with nonselective ß-blockers prevents decompensation in patients with clinically significant portal hypertension, changing the previous paradigm based on the presence of varices. In patients with acute variceal hemorrhage at high risk of failure with standard treatment (defined as those with a Child-Pugh score of 10-13 or those with a Child-Pugh score of 8-9 with active bleeding at endoscopy), a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) improves the mortality rate and has become the standard of care in many centers. In patients with bleeding from gastrofundal varices, retrograde transvenous obliteration (in those with a gastrorenal shunt) and/or variceal cyanoacrylate injection have emerged as alternatives to TIPS. In patients with ascites, emerging evidence suggests that TIPS might be used earlier, before strict criteria for refractory ascites are met. Long-term albumin use is under assessment for improving the prognosis of patients with uncomplicated ascites and confirmatory studies are ongoing. Hepatorenal syndrome is the least common cause of acute kidney injury in cirrhosis, and first-line treatment is the combination of terlipressin and albumin. Hepatic encephalopathy has a profound impact on the quality of life of patients with cirrhosis. Lactulose and rifaximin are first- and second-line treatments for hepatic encephalopathy, respectively. Newer therapies such as L-ornithine L-aspartate and albumin require further assessment.

Nutrition in Patients with Type 2 Diabetes: Present Knowledge and Remaining Challenges.

Unhealthy behaviours, including diet and physical activity, coupled with genetic predisposition, drive type 2 diabetes (T2D) occurrence and severity; the present review aims to summarise the most recent nutritional approaches in T2D, outlining unmet needs. Guidelines consistently suggest reducing energy intake to counteract the obesity epidemic, frequently resulting in sarcopenic obesity, a condition associated with poorer metabolic control and cardiovascular disease. Various dietary approaches have been proposed with largely similar results, with a preference for the Mediterranean diet and the best practice being the diet that patients feel confident of maintaining in the long term based on individual preferences. Patient adherence is indeed the pivotal factor for weight loss and long-term maintenance, requiring intensive lifestyle intervention. The consumption of nutritional supplements continues to increase even if international societies do not support their systematic use. Inositols and vitamin D supplementation, as well as micronutrients (zinc, chromium, magnesium) and pre/probiotics, result in modest improvement in insulin sensitivity, but their use is not systematically suggested. To reach the desired goals, patients should be actively involved in the collaborative development of a personalised meal plan associated with habitual physical activity, aiming at normal body weight and metabolic control.

An innovative hyperbaric hypothermic machine perfusion protects the liver from experimental preservation injury.

PURPOSE: Hypothermic machine perfusion systems seem more effective than the current static storage to prevent cold ischemic liver injury. Thus, we test an innovative hyperbaric hypothermic machine perfusion (HHMP), which combines hyperbaric oxygenation of the preservation solution and continuous perfusion of the graft. METHODS: Rat livers were preserved with Celsior solution according to 4 different modalities: normobaric static preservation; hyperbaric static preservation at 2 atmosphere absolute (ATA); normobaric dynamic preservation, with continuous perfusion; hyperbaric dynamic preservation, with continuous perfusion at 2 ATA. After 24 h cold preservation, we assessed different parameters. RESULTS: Compared to baseline, livers preserved with the current static storage showed severe ultrastructural damage, glycogen depletion and an increased oxidative stress. Normobaric perfused livers showed improved hepatocyte ultrastructure and ameliorated glycogen stores, but they still suffered a significant oxidative damage. The addition of hyperbaric oxygen produces an extra benefit by improving oxidative injury and by inducing endothelial NO synthase (eNOS) gene expression. CONCLUSIONS: Preservation by means of the present innovative HHMP reduced the liver injury occurring after the current static cold storage by lowering glycogen depletion and oxidative damage. Interestingly, only the use of hyperbaric oxygen was associated to a blunted oxidative stress and an increased eNOS gene expression.

Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis.

The endocannabinoid system is involved in the pathogenesis of liver fibrosis. Although many substances have been proved to reduce fibrosis in experimental models of chronic liver injury, most of them appear to be effective only if given as a prophylactic or early treatment. This study aimed to explore the effect of pharmacological antagonism of the endocannabinoid cannabinoid type 1 (CB1) receptor started after the stage of full-blown cirrhosis had been reached. Wistar-Han rats with carbon tetrachloride (CCl(4))-induced cirrhosis were randomized to receive the CB1 receptor antagonist Rimonabant (10 mg/kg/day) or the vehicle for 2 weeks. Age-matched healthy rats served as controls. Liver fibrosis was assessed using Sirius red staining, hydroxyproline concentration and α-smooth muscle actin expression. Hepatic gene expression of mediators of fibrogenesis and inflammation were evaluated by real-time PCR. We also assessed the hepatic expression of CB1 and CB2 receptors and that of the enzymes implicated in the endocannabinoid metabolism. Fibrosis was significantly reduced in rats treated with Rimonabant compared with rats receiving the vehicle. CB1 receptor antagonism limited the gene upregulation of fibrogenic and inflammatory mediators occurring in untreated cirrhotic rats. CB1 and CB2 receptor expression was increased in cirrhotic animals. Interestingly, pharmacological CB1 receptor antagonism was associated with a further induction of the CB2 receptor expression. Regression of fibrosis can be achieved by pharmacological blockade of the CB1 receptor even when started in an advanced stage of the disease. This effect is associated with the suppression of pro-fibrogenic and inflammatory mediators and may have been indirectly favoured by the induction of CB2 receptor expression.

The nutritional status modulates preservation-reperfusion injury in rat fatty liver.

BACKGROUND: Microcirculation disturbances are essential factors of preservation injury in fatty liver. However, hepatocyte injury is also markedly excessive in fatty liver resulting, at least in part, from energy metabolism impairment and oxidative stress. Thus, this study aimed to determine whether nutritional status influences preservation injury in fatty liver and whether energetic substrate supplementation, alone or with a vasodilator, is protective. MATERIALS AND METHODS: Normal or fatty livers induced by a choline-deficient diet were isolated from fed and fasted rats, preserved in University of Wisconsin solution at 4 degrees C for 18 h, and then reperfused with Krebs-Henseleit solution at 37 degrees C for 120 min. Fasted rats with fatty liver were also treated as follows: (1) Glucose supplementation: rats had access to a glucose solution for 18 h prior procurement; (2) Prostaglandin (PG): alprostadil was continuously infused during reperfusion; (3) Combined treatment: Glucose supplementation + PG. RESULTS: Fasting-induced liver injury was significantly greater in fatty than normal liver. In fatty livers from fasted rats, all treatments reduced the alanine aminotransaminase release. Hepatic oxygen consumption improved in the glucose and glucose + PG groups, while PG infusion had no effect. Glucose supplementation did not affect portal pressure, which, in contrast, was reduced in livers receiving PG. Finally, all treatments lowered oxidative injury. CONCLUSIONS: Preservation injury in fatty liver is greatly related to nutritional status. Energetic substrate supplementation may represent a clinically feasible protective strategy and a multistep approach adding vasodilators could offer further benefit by acting on different pathogenetic mechanisms.