The latest medical research on Hepatology

Carvedilol is a non-selective β-blocker (NSBBs) with anti-α1-adrenergic activity, more effective than traditional NSBBs in reducing portal-pressure (HVPG). However, 35%-45% of patients still have insufficient HVPG-decrease. Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects. We investigated whether the addition of simvastatin improves the efficacy of carvedilol on HVPG in cirrhosis with severe portal-hypertension and suboptimal response to traditional-NSBBs.

Patients with cirrhosis and high-risk varices referred for primary prophylaxis were consecutively included. HVPG was measured at baseline and again after i.v.propranolol. Suboptimal responders (HVPG-decrease <20%) were treated with carvedilol and were randomized to double-blind administration of placebo or simvastatin. Chronic HVPG response was assessed after 4-6-weeks, repeating HVPG-measurements after a standard liquid meal to estimate endothelial dysfunction. Plasma samples were obtained before each study to investigate inflammatory parameters.

Of 184 eligible patients, 82 were randomized to carvedilol+simvastatin (N=41) or carvedilol+placebo (N=41). Baseline characteristics were similar. HVPG significantly decreased with both, carvedilol+simvastatin (18.6±4-to-15.7±4 mm Hg, p<0.001) and carvedilol+placebo (18.9±3-to-16.9±3 mm Hg, p<0.001). The decrease was greater with carvedilol+simvastatin (2.97±2.5 vs. 2.05±1.6 mm Hg, p=0.031). An HVPG-decrease ≥20% occurred in 37% versus 15% patients respectively (OR:3.37, 95% CI=1.15-9.85; p=0.021). With test-meal, HVPG increased in both groups (p<0.01), although carvedilol+simvastatin attenuated such increment (12±8% vs. 23±16%, p<0.001). Cytokine levels (IL-6,MCP-1,MDA) decreased significantly more with carvedilol+simvastatin (p<0.01). Incidence of adverse events was similar.

In patients with severe portal hypertension (all with high-risk varices) and suboptimal hemodynamic response to traditional NSBBs, combined therapy with carvedilol plus simvastatin significantly enhances the portal-pressure reduction achieved with carvedilol-monotherapy, improves endothelial dysfunction and reduces pro-inflammatory cytokines.

Liver transplant (LT) for Transplant Oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns on mid-long term survival and its impact on waiting list.

We conducted four systematic reviews of all series on TO indications (intrahepatic (iCC) and perihilar cholangiocarcinoma (phCC)), liver metastases from neuroendocrine tumors (NET) and colorectal cancer (CRLM)) and compared them using patient-level meta-analyses to data obtained from UNOS database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan criteria for NET). A total of 112.014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494 and 103 patients obtained from meta-analyses on iCC and phCC, and liver metastases from NET and CRLM, respectively. Five-years overall survival was 53,3%, 56,4%, 68,6% and 53,8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second and third LT and and not statistically significant different to LT in recipients>70 years and high BMI.

Liver transplantation for TO indications has adequate 5-years survival rates, mostly when performed under the selection criteria available in literature (Mayo-like protocols for phCC, SECA-2 for CRLM and Milan for NET). Despite concerns on its impact on waiting list, some other LT indications are being performed with lower survival. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria.