How to do the prevention of (first) decompensation?

Compensated cirrhosis is defined by the absence of present or past complications of cirrhosis. The transition from compensated to decompensated cirrhosis leads to an increased mortality risk.

Compensated cirrhosis can be divided into 2 stages, based on the absence or presence of clinically significant portal hypertension (CSPH). Patients with CSPH are at increased risk of decompensation. The goal of treatment in compensated cirrhosis is to prevent complications that define decompensation.

Prevention of decompensation is especially relevant in compensated patients with CSPH and/or oesophageal or gastric varices due to their higher risk of developing decompensation.

The events that define decompensation in a compensated patient are overt ascites (or pleural effusion with increased serum ascites albumin gradient [>1.1 g/dl]), overt hepatic encephalopathy (West Haven grade ≥II) and variceal bleeding.

Other relevant liver-related events in compensated cirrhosis are the development of superimposed liver injury/ACLF and HCC.

Insufficient data are available regarding whether a minimal amount of ascites only detected in imaging procedures, minimal hepatic encephalopathy, and occult bleeding from portal hypertensive gastroenteropathy (PHG) can be considered as decompensation.

Limited data suggest that jaundice alone (in non-cholestatic aetiologies) may be the first manifestation of cirrhosis in a minority of patients; however, its definition, whether it should be considered true first decompensation or if it reflects superimposed liver injury/acute-on-chronic liver failure (ACLF) in compensated cirrhosis requires further research.

Non-hepatic comorbidities are frequent in patients with compensated cirrhosis, can adversely impact prognosis, and should be specifically dealt with.

There is insufficient data to draw definitive conclusions on the impact of sarcopenia and frailty on the natural history of compensated cirrhosis.

Bacterial infections are frequent in compensated patients with CSPH, can lead to decompensation (ascites, variceal bleeding, hepatic encephalopathy) and, consequently, adversely affect natural history.

There is insufficient data as to whether infections are frequent in compensated cirrhosis without CSPH and whether they may impact prognosis per se.

Superimposed liver damage, such as (acute) alcoholic hepatitis, acute viral hepatitis (HEV, HAV), HBV flares or drug-induced liver injury can precipitate decompensation.

Other factors such as HCC and major surgery can precipitate decompensation of cirrhosis in patients with CSPH.

Treatment with non-selective beta blocker(s) [NSBBs] (propranolol, nadolol or carvedilol∗) should be considered for the prevention of decompensation in patients with CSPH. *In contrast with the traditional NSBBs (i.e. propranolol and nadolol), carvedilol has intrinsic anti-alpha adrenergic vasodilatory effects that contribute to its greater portal pressure reducing effect.

Carvedilol is the preferred NSBB in compensated cirrhosis, since it is more effective at reducing HVPG, has a tendency towards greater benefit in preventing decompensation and towards better tolerance than traditional NSBBs and has been demonstrated to improve survival compared to no active therapy in compensated patients with CSPH.

The decision to treat with NSBBs should be taken when clinically indicated, independent of the possibility of measuring HVPG.

Patients with compensated cirrhosis who are on NSBBs for the prevention of decompensation do not need a screening endoscopy for the detection of varices since endoscopy will not change management.

There is no evidence that endoscopic therapies such as endoscopic band ligation or glue might prevent ascites or hepatic encephalopathy.

In compensated patients with high-risk varices who have contraindications or intolerance to NSBBs, endoscopic band ligation is recommended to prevent first variceal bleeding.

There is no indication at present to use NSBBs in patients without CSPH.

Although a single study suggested that cyanoacrylate injection is more effective than propranolol in preventing first bleeding in patients with large type 2 gastro-oesophageal varices or isolated type 1 gastric varices, there were no differences in survival. However, NSBBs are indicated in these patients to prevent decompensation. Further studies are required in these patients using new therapeutic approaches in addition to NSBBs.

There is no indication at present for balloon-occluded retrograde (antegrade) transvenous obliteration (BRTO or BATO) or TIPS in primary prophylaxis of gastric variceal bleeding in compensated patients.

References:

Corrigendum to ‘Baveno VII – Renewing consensus in portal hypertension’ [J Hepatol (2022) 959-974] Journal of Hepatology, Vol. 77, Issue 2