Cirrhosis: A Term in Need of a Makeover

What Is Wrong with the Current Concept of Cirrhosis?

The term cirrhosis implies a uniform end-stage liver disease that is irreversible. The condition denoted by the term cirrhosis, however, encompasses a wide spectrum of diseases in terms of etiopathogenesis, as well as clinical and pathologic features. In addition, it is well recognized that cirrhosis is not a uniform process across diseases or individuals. By implying a single homogeneous disease entity, the term cirrhosis ignores this complexity.

The clinical spectrum of cirrhosis varies from an asymptomatic compensated phase to one of severe decompensation and liver failure leading to death. Cirrhosis can thus be divided into clinical stages, each with distinct manifestations and prognosis. The clinical manifestations correlate well with hepatic venous pressure gradient, which is undoubtedly a consequence of parenchymal and vascular remodeling that occur at a microanatomic level. By implying a uniform process, the term cirrhosis is insensitive to clinical stages and the dynamic nature of the cirrhotic process.

The path of progression of cirrhosis is not uniformly linear. The course of disease may be accelerated, halted, or even reversed with effective therapies. By implying an end-stage irreversible disease, the term cirrhosis renders redundant and thus impedes initiatives at pathologic staging, correlation of pathologic findings with clinical manifestations, and identifying prognostic and predictive markers on surgical pathology material.

Regression of cirrhosis is being increasingly documented especially when the underlying etiologic agent, such as a hepatitis virus (see Fig. 14.11, Fig. 40.1, Fig. 40.2 ) or accumulated iron, is removed. Intense efforts are also underway to identify therapeutically beneficial antifibrotic agents and epigenetic modifiers. By implying an end-stage irreversible process, the term cirrhosis ignores the dynamic nature and potential reversibility of the process.

It is thus evident that the singular term cirrhosis is clearly inadequate in describing a multiplicity of nonhomogeneous clinical and pathologic processes. It is also by itself inadequate in conveying pertinent clinical and prognostic information. This shortfall can be adequately addressed by qualifiers and additional information. There is thus an emphasis on more comprehensive reporting of microscopic features and an attempt to correlate them with clinical data such as hepatic venous pressure gradient (HVPG). A statement about the size and number of septa, size and number of nodules, and substage by the Laennec schema (see later) would be clinically meaningful. Presence or absence of features of regression should be reported. Large-scale studies to guide and validate current knowledge are however unavailable. Whether cirrhosis as a term should be abandoned because of its negative prognostic connotations remains to be determined. Regardless, a change in concept of a “uniform, end-stage and irreversible” process is clearly warranted.

Cirrhosis Is Not a Homogeneous Disease

Fibrosis and nodularity evolve over a long time through a process that is neither linear nor predictable and that varies among diseases of different etiologies and among individual patients. The process is also dynamic with continuous remodeling, which is affected by the activity of the underlying disease, therapeutic interventions, and local factors such as vascular obliteration. Thus, no one biopsy looks like another with variation in the number of size and nodules, size and the number of septa, degree of inflammation and ductular reaction, as well as other pathologic findings, all of which might be expected to influence clinical manifestations and prognosis.