Jean-Pierre Benhamou clinical state-of-the-art: Is it time to abandon the term cirrhosis?

 Cirrhosis and complications
 Webcasted session

Main Plenary
English
State of the Art
13 April 2018 10:30 - 11:00

Jaime BoschJaime Bosch, MD, PhD, FRCP

Guest Professor of Hepatology, Swiss Liver Centre, Inselspital, Department of Biomedical Research, University of Bern, Switzerland

Cirrhosis of the liver is an anatomic diagnosis for a common final phase of several advanced chronic liver diseases. It is characterized by a total remodelling of the normal liver architecture that is substituted by the diffuse formation of regenerative nodules separated by fibrous scar tissue. Cirrhosis may be the consequence, among others, of chronic viral hepatitis (B, D, C, and E), of alcohol abuse, metabolic disorders -either acquired (NAFLD) or congenital (hemochromatosis, Wilson disease, alpha-1 AT deficiency), toxic agents (hepatotoxic drugs), chronic autoimmune hepatitis, and of chronic biliary or cholestatic diseases (PBC, PSC, biliary obstruction, biliary atresia, cystic fibrosis).

For many years “cirrhosis” has been a feared diagnosis, since it has been considered to imply an ominous prognosis. However, during the past decades it has become clear that cirrhosis may be for many years totally asymptomatic, a poor prognosis being only associated after development of serious complications. Yet, the anatomical diagnosis of cirrhosis does not correlate well with prognosis. Moreover, liver biopsy is invasive and thus cannot be repeated every 1-2 years to verify how histology is evolving; in addition, it carries a >20% risk of missing the diagnosis, has significant interobserver variability, and not even pathologists like to use the term cirrhosis nowadays. On the other hand, the clinical diagnosis of “cirrhosis” is inaccurate, and even with the newer non-invasive tools many cases may wrongly classified, dependent on how strict are the criteria for ruling-in or ruling-out “cirrhosis”. On top of that, the term cirrhosis is polluted by the stigmata of being a “self-inflicted disease caused by chronic alcoholism”, which as stated is very frequently not true. Finally, the pathophysiology of the complications of cirrhosis changes from early to advanced phases, which has also implications in terms of therapeutic targets and strategies. Because of these caveats, at the past Baveno VI consensus conference on portal hypertension it was proposed to substitute the term “cirrhosis” by the term “advanced chronic liver disease” or ACLD.

The evolution of ACLD follows several stages. The first stage is compensated ACLD, where the disease is frequently asymptomatic and has an excellent prognosis. Within this phase we can distinguish two substages according to the presence or not of “clinically significant portal hypertension” (a hepatic vein pressure gradient, HVPG, of 10 mmHg or above) or of varices at endoscopy (or of collaterals on abdominal imaging). The substage without CSPH has an excellent prognosis (1-year mortality of 1.5%) and is potentially reversible by correcting the cause of the ACLD and by adopting a safe life-style. At this stage the patients have not yet developed a hyperkinetic circulation and agents such as non-selective beta-blockers (NSBB) are useless. A rational target for non etiology-specific therapy would be acting on liver fibrosis and on hepatic microvascular endothelial dysfunction. The substage with CSPH still has a good prognosis (1-year mortality of 2%), but carries a 20-40% 2-year risk of transitioning to the stage of decompensated cirrhosis. Treatments are being developed to prevent transitioning to decompensation. In addition to strategies used when there is no CSPH, here NSBB may be effective in decreasing the risk of decompensation.

The stage of decompensated cirrhosis starts with the development of severe clinical complications related to portal hypertension and advanced liver failure: ascites (and related complications), variceal bleeding, overt hepatic encephalopathy or jaundice. Prognosis is much worse than in compensated ACLD, and goes from a 10% risk of death at 1-year after experiencing variceal bleeding alone, to about 20% in patients with non-bleeding complications, and 30% when both bleeding and nonbleeding manifestations of decompensation have arisen. After decompensation the reversibility of the ACLD is doubtful or very unlikely and the only curative treatment is liver transplantation, although there are effective medical treatments to delay the evolution to death or transplantation, including endoscopic therapy, NSBB, statins and TIPS. Other novel drugs are being tested.

Development of hepatocellular carcinoma may occur at any stage in ACLD, although it is much more frequent after developing CSPH. The clinical stage of ACLD also influences the choice of treatment for liver cancer.


Presentations

Is it time to abandon the term cirrhosis?
Jaime Bosch - Spain
13 April 2018 10:30 - 11:00