Natural History Study of Non-A, Non-B Post-Transfusion Hepatitis (NANB-TAH)

Objectives

This extended follow-up study of 5 major prospective studies of transfusion-associated hepatitis conducted in the US between 1967 and 1980, attempted to address the uncertainty about the frequency progression to clinically symptomatic and debilitating chronic liver disease and the frequency of fatal liver disease. The study, designed to track both mortality and morbidity of transfusion-associated non-A, non-B hepatitis, was a natural history evaluation that began at the time of disease onset. It also included a concurrent control group that could be evaluated, and that the study subjects were monitored for almost 25 years.

Background

Prior to this study, little was known about the long-term consequences of non-A, non-B hepatitis. Most studies examined the short-term prognosis following acute infection which was characterized by mild but persistent inflammation. However, reports of late-onset cirrhosis, liver failure or even hepatocellular carcinoma were accumulating from patients with more than 10 years of follow-up. The frequency, rate of development and contribution to mortality of these sequelae of transfusion-associated non-A, non-B hepatitis were not well established.

Subjects

Of the total 6438 subjects who entered the original 5 studies, 1552 were included in this study. There were 568 subjects with non-A, non-B hepatitis and 984 control subjects (526 were first controls, and 458 were second controls). Thirty-eight subjects with hepatitis had no matched controls and 76 had only one control.

Design

Researchers traced patients with two control subjects with transfusion related non-A, non –B hepatitis who had been identified in 5 separate studies conducted between 1967 and 1980. Each patient was matched with two control subjects who received transfusions but did not have hepatitis. They were matched based on five categorical variables: the initial treatment center, sex, race (black or non-black), use of hepatitis immunoprophylaxis, and the presence or absence of a history of alcoholism; and three continuous variables: age, the number of units of blood transfused, and the date of transfusion. The mortality rates in the three groups were determined with use of data from National Death Index and Social Security Death Tapes. Cause specific mortality rates were determined by reviewing death certificates.

Conclusions

The data indicated that the frequency of death from all causes among transfusion recipients whom non-A, non-B hepatitis had developed an average of 18 years earlier in virtually identical to that in a carefully matched group of transfusion recipients in whom hepatitis did not develop. There was no increase in the mortality from all causes after transfusion associated non-A, non-B hepatitis, although there was a small, but statistically significant increase in the number of deaths related to liver disease. With an additional 7 years of follow-up, the liver-related mortality rate attributable to chronic hepatitis C increased among the cases compared to the controls. Additional follow-up of subjects, restricted to the 3 studies with archived original sera was extended to approximately 25 years. There remained no increase in the mortality from all causes after transfusion associated non-A, non-B hepatitis.

Publications

Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992; 327(27):1906-11.

Seeff LB, Miller RN, Rabkin CS, Buskell-Bales Z, Straley-Eason KD, Smoak BL, Johnson LD, Lee SR, Kaplan EL. 45-year follow-up of hepatitis C virus infection in healthy young adults. Ann Intern Med. 2000; 132(2):105-11.

Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, Seeff LB; National Heart, Lung, and Blood Institute Study Group. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med. 2001; 134(2):120-4.

Lin HJ, Seeff LB, Barbosa L, Hollinger FB. Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: divergence over time. Hepatology. 2001; 34(2):424-9.

Seeff LB, Hollinger FB, Alter HJ, Wright EC, Cain CM, Buskell ZJ, Ishak KG, Iber FL, Toro D, Samanta A, Koretz RL, Perrillo RP, Goodman ZD, Knodell RG, Gitnick G, Morgan TR, Schiff ER, Lasky S, Stevens C, Vlahcevic RZ, Weinshel E, Tanwandee T, Lin HJ, Barbosa L. Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study. Hepatology. 2001; 33(2):455-63.

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