Approximately 85% of persons with acute hepatitis C de-
Infection with the hepatitis C virus (HCV) is a problem of much current concern. Although acute hepatitis C is com-velop chronic hepatitis as determined by persistently abnormal serum enzymes and/or viremia (hepatitis C virus [HCV] monly an asymptomatic and seemingly mild illness, the viral infection nearly always persists, resulting in the development RNA). Both the acute and chronic illnesses are predominantly asymptomatic. For this reason and because the chronic illness of chronic hepatitis. By convention, chronic hepatitis is believed to have developed when the serum enzymes remain runs an extremely protracted course, it has been difficult to accurately define the frequency and rate of progression to abnormal for at least 6 months. An additional subgroup continue to show persistent infection (HCV RNA reactivity) in symptomatic or end-stage liver disease, specifically cirrhosis and hepatocellular carcinoma (HCC). Three evaluation strate-the absence of increased serum enzyme levels. Unfortunately, these events usually take place in an oblivious host who gies have been used. The first, prospective studies beginning from disease onset, have identified over 8 to 14 year follow-up generally continues to remain asymptomatic. Once chronicity ensues, it is believed that the disease may range through periods that morbidity (symptoms, cirrhosis) and mortality (hepatic failure, HCC) are modest in frequency. The second, incrementally advancing stages of histologically defined chronic hepatitis, progress to cirrhosis, and culminate in the prospective studies of subjects with already established chronic liver disease, have demonstrated high rates of devel-development of hepatocellular carcinoma (HCC). Some authorities believe that these sequentially progressive changes opment of cirrhosis, HCC, and mortality over relatively short follow-up periods. The third, retrospective/prospective (non-are inevitable and will occur in most chronically infected persons provided they do not die first from another lethal concurrent prospective) studies, has consisted of follow-up of recipients of HCV-contaminated immunoglobulin and of illness. Others believe that only a proportion of infected persons will develop progressive disease and that attention transfusion recipients from five enzyme-monitored transfusion studies of the early 1970s. The former study identified should therefore focus on establishing as early as possible who is likely to show advancing disease and on attempting to no mortality, trivial morbidity, and minimal cirrhosis 17 years after infection. The latter, involving hepatitis cases and define factors that might be responsible for such progression.
These contradictory views can be resolved only by conduct-matched nonhepatitis controls studied over a 20-year period, demonstrated no increase in all-cause but a slight increase in ing appropriate long-term studies of the natural history of the disease. liver-related mortality. Clinically evident chronic liver disease was noted to be minimal among those in follow-up with bio-
INGREDIENTS FOR CONDUCT OF AN ACCURATE chemically defined chronic hepatitis whose biopsy specimens NATURAL HISTORY STUDY OF CHRONIC showed no cirrhosis, but common among those with histologi-HCV INFECTION cally detected cirrhosis. More than 90% of subjects with an
There has been much difficulty in designing and undertakoriginal diagnosis of transfusion-related hepatitis C have reing suitable studies that can convincingly define the natural mained positive for antibody to HCV (anti-HCV), most with history of chronic HCV infection. Indeed, the difficulties are persistent viremia. Two thirds of the anti-HCV-positive indisuch that an absolute answer may never be fully realized.
viduals have biochemically defined chronic hepatitis, whereas
With regard to hepatitis C, it seems apparent that certain one third have persistently normal enzymes. Taken together, critical items must be incorporated into the design of a natuavailable data suggest that in the first two decades after infecral history study if it is to be truly informative. These include tion, mortality and morbidity are modest in frequency. Both the need for the following: 1) to accurately establish onset can be expected to increase as the disease advances to the of the initial acute disease to properly determine disease duthird and fourth decades after acute infection, especially ration; 2) to identify and evaluate the full spectrum of acute among those with established cirrhosis. The outcome among disease to avoid the bias of focussing evaluation on the more those with chronic hepatitis but without cirrhosis remains to obvious and more severe forms of illness; 3) to track the be determined. (HEPATOLOGY 1997;26(Suppl 1):21S-28S.)
process to its resolution or to its adverse disease end point, regardless of the duration of the process, which may extend Abbreviations: HCV, hepatitis C virus; HCC, hepatocellular carcinoma; anti-HCV, for decades; 4) to evaluate outcome without instituting treatantibody to hepatitis C virus; ALT, alanine aminotransferase.