Portal hypertension is the primary pathophysiological cause of decompensated events and worsening liver function in patients with cirrhosis. Non-selective beta-blockers (NSBBs), as the preferred treatment for reducing portal hypertension and preventing esophagogastric variceal bleeding, have been widely used in clinical practice. There is also a trend toward their application in preventing all decompensated events related to portal hypertension.
At the 58th European Association for the Study of the Liver (EASL) International Liver Congress 2023, Doctor Thomas Reiberger from the Medical University of Vienna, Austria, attended the “Meet the experts: NSBB in cirrhosis” session, where he discussed and shared insights on the hotly debated issues surrounding the use of third-generation NSBB Carvedilol in various stages of cirrhosis. Hepatology Digest reporting team had an exclusive interview with Doctor Thomas Reiberger to delve into these topics. Here is a summary of their discussion:
Hepatology Digest:NSBBs have seen widespread use in patients with cirrhosis. Could you please talk about the recent clinical applications of NSBBs and guideline recommendations?
Doctor Thomas Reiberger: Generally, we follow the Baveno guidelines, with the latest being Baveno VII, recently published in the Journal of Hepatology. The primary prophylaxis for esophagogastric variceal bleeding should preferentially use beta-blockers over band ligation. Beta-blockers not only prevent variceal bleeding but also other non-bleeding compensation events. The evidence for this comes from the PREDESCI study, which randomized patients with clinically significant portal hypertension into beta-blocker and placebo groups. The results showed a significantly lower rate of compensation events in patients receiving beta-blocker therapy.
It’s worth noting that this study mainly relied on measuring hepatic venous pressure gradient (HVPG). The question now is whether we can use non-invasive markers to identify patients who would benefit. While there isn’t strong evidence, many indirect pieces of evidence suggest that non-invasive markers, such as liver stiffness exceeding 25 kPa, can also indicate a high risk of portal hypertension in patients. However, this liver stiffness threshold may not apply to obese patients (BMI over 30 kg/m2) and is even more uncertain in patients with non-alcoholic steatohepatitis (NASH).
Hepatology Digest : Carvedilol is a third-generation NSBB. What are its advantages over traditional NSBBs like Propranolol?
Doctor Thomas Reiberger: We tend to prefer Carvedilol over Propranolol because Carvedilol, in addition to blocking beta-1 and beta-2 receptors, also blocks the alpha-1 adrenergic receptors. These alpha-1 receptors are located in the liver sinusoids and are responsible for vasoconstriction. By blocking these alpha-1 adrenergic receptors with Carvedilol, you reduce sinusoidal vasoconstriction, decrease hepatic resistance, increase sinusoidal flow, and further lower portal pressure.
We have observed in multiple studies that switching from Propranolol to Carvedilol can further reduce portal pressure and improve hemodynamic response rates. This can lead to at least a 10% reduction in primary prophylaxis and a 20% reduction in HVPG in secondary prophylaxis. We’ve tested this in both scenarios, and Carvedilol consistently achieves a higher hemodynamic response rate, likely due to its additional alpha-1 adrenergic blockade.
Hepatology Digest : Can Carvedilol be used in compensated cirrhosis patients without endoscopy?
Doctor Thomas Reiberger: If you know varices are present, it’s recommended and very safe to use Carvedilol. For compensated cirrhosis patients with varices, not using Carvedilol could pose problems. You can use non-invasive markers to assess this, with the most prominent being a liver stiffness value exceeding 25 kPa. In such cases, you can use Carvedilol without endoscopy. Another option is measuring spleen stiffness, with a critical value of over 50 kPa indicating a high risk of portal hypertension. So, in patients with no endoscopy but spleen stiffness exceeding 50 kPa, you can also use Carvedilol.
Hepatology Digest : Can Carvedilol be used in cirrhosis patients with ascites and no varices?
Doctor Thomas Reiberger: Using Carvedilol in patients with ascites but no varices goes beyond primary bleeding prophylaxis. However, because these patients have ascites due to clinically significant portal hypertension, I personally would continue treatment with Carvedilol, although this is not evidence-based. In this scenario, I would choose to continue treatment because clinically significant portal hypertension remains even without varices. If varices and ascites coexist, Carvedilol can be used. In principle, as long as there are no side effects like dizziness or hypotension, you can continue Carvedilol. If the systolic blood pressure drops below 110 mmHg, switching from Carvedilol to Propranolol may be necessary.
Hepatology Digest : Should NSBBs be discontinued if ascites resolves in decompensated cirrhosis?
Doctor Thomas Reiberger: Recompensation is defined as the resolution of ascites, no bleeding for at least 12 months, and the disappearance of hepatic encephalopathy. Effective antiviral therapy (especially for hepatitis B and C patients) and alcohol cessation have allowed patients to achieve recompensation.
However, it’s important to note that even though all these treatments indicate an improved condition, portal hypertension may still be present. As long as clinically significant portal hypertension is present, we recommend continuing beta-blocker therapy. There is ongoing debate about whether non-invasive markers can be used in recompensated cirrhosis patients to exclude portal hypertension.
In hepatitis C patients without cirrhosis (liver stiffness below 12 kPa), with normal platelet counts and recompensation, beta-blockers can be discontinued. In clinical practice, many patients may continue with beta-blockers, which generally should not harm them. Gastroscopy can be considered in these patients. If no varices are visible, you can discontinue beta-blockers. This is my personal recommendation. Non-invasive markers suggest liver stiffness below 12 kPa, normal platelet counts, or repeat gastroscopy showing the disappearance of varices. If any of these criteria are met, you can safely stop beta-blockers.
