Clinical states of cirrhosis and competing risks

Abstract

The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of these disease states prompted the concept of clinical states of cirrhosis. A multistate approach has been considered to describe the clinical course of the disease. Such an approach requires the assessment of the probabilities of different outcomes in each state, which compete with each other to occur first and mark the transition towards a different state. This requires the use of competing risks analysis, since the traditional Kaplan-Meier analysis should only be used in two-state settings. Accounting for competing risks also has implications for prognosis and treatment efficacy research. The aim of this review is to summarise relevant clinical states and to show examples of competing risks analysis in multistate models of cirrhosis.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

“…Although new onset of jaundice is commonly referred to as a decompensating event in natural history studies, (31) we did not incorporate jaundice in the definition of hepatic decompensation, because this term is poorly defined. (32) This is in line with previous studies investigating risk factors for hepatic decompensation.…”

Treatment of Oesophageal Varices in Liver Cirrhosis

“…Besides the blood pressure within the vessel, the risk of bleeding is determined by morphological parameters (variceal size and location) [1,2,4]. In compensated cirrhosis without oesophageal varices, such collaterals develop at a rate of 7-8% per year [5].…”

Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension

“…In this stage, the patient with chronic liver disease and/or chronic risk factors for liver disease (e.g., alcohol ingestion, HCV infection) has histological, imaging, or elastographic evidence of cirrhosis, but has not developed any decompensating events (ascites, variceal hemorrhage, or encephalopathy). Median survival is around 15 years …”

“…This stage is characterized by the presence of clinical complications, specifically ascites, variceal hemorrhage, encephalopathy, and jaundice (although the latter is very rare as a first decompensating event) . Median survival is 1.5 years . Type and number of decompensating events is of prognostic importance as is the presence of further complications of decompensating events such as hepatorenal syndrome (“further” decompensation”).…”

“…A surrogate would not only reduce sample size and study duration, but could also be considered appealing because it would be a substitute for a more‐severe clinical outcome. Because patients with compensated cirrhosis have an overall low rate of decompensation, it has been suggested that changes in HVPG could be used as a surrogate endpoint to support the approval of new treatments for PH (within the FDA accelerated approval framework).…”