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

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Accession Number

Study Type
Epidemiology Study

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
1988 - 2001

NHLBI Division

Dataset(s) Last Updated
January 3, 2018

Primary Publication URLs

Related Studies


Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No

Commercial Use Specimen Restrictions No

Non-Genetic Use Specimen Restrictions Based On Area Of Use Yes

Genetic Use Of Specimens Allowed? Yes

Genetic Use Area Of Research Restrictions Yes

Specific Consent Restrictions
Use of biospecimens is restricted to studies related to hepatitis.


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.


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.


Of the total 6438 subjects who entered the original 5 studies, that included the VA Cooperative Study of the Efficacy of Hepatitis Immune Serum Globulin for the Prevention or Modification of Post-Transfusion Hepatitis (VA2-TAH) and the Transfusion-Transmitted Viruses Study (TTVS), 1765 subjects were included in this study including 1552 non-A, non-B cases and controls (568 cases and 984 matched controls) and 213 hepatitis B cases and controls (79 cases and 134 matched controls). Thirty-eight of the non-A, non-B cases had no matched controls and seventy-six had only one control. Eight of the hepatitis B cases had no matched controls and eight had only one control.

A total of 311 subjects in the NANB-TAH study were recruited from the VA2-TAH study of which 308 subjects can be linked to the available dataset. A subset have biospecimens available from the VA2-TAH study period. A total of 501 subjects in the TTVS study subsequently were enrolled and followed in the NANB-TAH study although linkage at the subject level is no longer available.


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.


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.


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.

Additional Details


Cases: 647

Control 1: 597

Control 2: 521

 CaseControl 1Control 2All
 CaseControl 1Control 2All
 CaseControl 1Control 2All
Not Black53883.1550384.2544284.84148384.02

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

Visits (Vials):


Month 11,2801,280
Month 23838
Month 3972972
Month 43030
Month 55656
Month 67575
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Month 8123123
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Visits (Subjects):


Total number of subjectsAverage volume (ml) per subject
Month 15796.32
Month 2196.86
Month 35027.27
Month 4146.14
Month 5257.16
Month 6357.39
Month 7437.09
Month 8557.52
Month 9547.00
Month 10457.73
Month 11377.79
Month 12395.81
Month 13375.57
Month 14306.49
Month 15315.36
Month 16304.92
Month 17325.72
Month 18326.80
Month 19306.48
Month 20237.85
Month 21217.50
Month 22188.64
Month 231310.19
Month 24811.44

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Resources Available

Specimens and Study Datasets

Materials Available

Study Documents

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