ABSTRACT
Hepatitis C has emerged in recent years as the most common basis for liver disease
in the United States, having infected an estimated 3.9 million people in this country
and an estimated 170 million worldwide. Currently, it is the predominant reason for
undergoing liver transplantation. The disease it causes is characterized by silent
onset in most infected individuals, a high rate of viral persistence, and the potential
for development of ever-worsening chronic liver disease, ranging from chronic hepatitis
to cirrhosis and occasionally to hepatocellular carcinoma. Such progression, when
it occurs, is also most commonly a silent process that may take 20-40, and occasionally
even more, years to reach its end point. Because of these characteristics, it has
been exceedingly difficult to accurately assess the natural history. Efforts to accomplish
this have consisted of retrospective, prospective, and cohort studies. The most concerning
data have derived from the retrospective study approach, generally performed at tertiary
referral centers. Because these centers commonly attract persons with existing chronic
liver disease, they have tended to describe a high rate of progression to cirrhosis
and cancer. This ``referral bias'' is avoided in the prospective and cohort study
approach, and data derived from these studies indicate a lower rate of progression
and a correspondingly higher rate of either recovery or minimal liver disease. In
this review, we briefly describe potential mechanisms of viral persistence; present
detailed information on outcomes that have derived from retrospective, prospective,
and cohort studies, involving both adults and children; examine the data regarding
progression of fibrosis and of progression to hepatocellular carcinoma; consider cofactors
that might enhance liver disease progression; and report the emerging data that suggest
that spontaneous viral clearance may be higher than is currently believed. We conclude
with the view that severe, life-threatening, progressive liver disease clearly occurs
in a sizable minority (perhaps 30%) of chronically infected persons but speculate
that fibrosis progression is neither linear or inevitable and hence that most hepatitis
C virus carriers will have either a stable nonprogressive course or such indolent
progression that they will die from an unrelated disease before the severe sequelae
of hepatitis C become manifest or will have a sustained ``curative'' response to therapy.
Although this view provides reasonable hope to the hepatitis C virus-infected individual,
it does not deny the enormous burden this infection presents as the result of its
high prevalence and global distribution. The sheer magnitude of the infected population
will result in a large number with severe life-threatening liver disease even if the
proportion of infected individuals that develop progressive disease is relatively
small.
KEYWORD
HCV - chronic hepatitis - fibrosis - cirrhosis
