The Course of Hepatitis C Viraemia in Transfusion Recipients Prior to Availability of Antiviral Ther

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From Journal of Viral Hepatitis

The Course of Hepatitis C Viraemia in Transfusion Recipients Prior to

Availability of Antiviral Therapy

Posted 04/03/2008

J. W. Mosley; E. A. Operskalski; L. H. Tobler; Z. J. Buskell; W. W. s; B.

Phelps; J. Dockter; C. Giachetti; L. B. Seeff; M. P. Busch

Summary and Introduction

Summary

Knowing the likely distribution of intervals from hepatitis C infection to first

RNA-negativity is important in deciding about therapeutic intervention.

Prospectively collected sera and data from the Transfusion-transmitted Viruses

Study (1974—1980) provide specific dates of infection and pattern of alanine

aminotransferase (ALT) elevations. We examined frequency, timing and correlates

of spontaneous resolution for 94 acutely infected transfusion recipients

followed for a median of 9.5 months. Later, follow-up sera (>10 years) were

available for 27 of the 94 cases from a Veterans Administration (VA) Study

(1989—1990). Twenty-five (27%) of the 94 cases were classified as probably

resolved during the episode itself. First RNA negativity occurred at 6—50 weeks

(median, 19.5 weeks) after infection, and 5—43 weeks (median, 11 weeks) after

ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12

others had 1—6 RNA-positive sera intercalated between first and last

RNA-negative results. RNA negativity, therefore, began variably and was

interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of

these 25 patients who were RNA-negative in the last study specimen had late,

Veterans Administration Study follow-up; none showed viraemia. Of the remaining

69 transfusion transmitted virus study recipients, whose last serum was

RNA-positive, two cleared viraemia after the last study serum but before late

follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last

positivity. RNA status, therefore, needs monitoring for many months before

judging the spontaneous outcome as transient negativity may occur. Resolution

was significantly more common in women and symptomatic cases; it was not

associated with viral load in the infectious donation, HCV genotype, or the

recipient's age.

Introduction

Hepatitis C virus (HCV) infection is characterized by a high frequency of

progression to chronic liver disease.[1] Acute infection is usually asymptomatic

and, therefore, frequently unrecognized unless suspected from epidemiological

circumstances. Thus, there are few cases in the 6 months after infection to

characterize the dynamics of viral replication and immune responses, or to

evaluate antiviral interventions. Throughout the 1990s, therefore, the focus of

treatment studies was on persons with already-established chronic hepatitis

C.[2] Although treatment of chronic infection has recently improved, the

presently available therapeutic agents still produce a sustained viral response

in only half of those with chronic genotype 1 infection.[3] In contrast, studies

of acute hepatitis C show a sustained response to antiviral treatment of 80 to

98%.[4-7] A recent study having an overall clearance rate of 71% showed its

subpopulation with good protocol adherence to have a level of 89%.[8]

Unfortunately, the presently available antiviral drugs usually have debilitating

physical and emotional effects that can be very devastating.[9] It is of

particular interest, therefore, that some recent studies indicate that

spontaneous clearance of viraemia may be more frequent than previously believed.

Its possible occurrence within several months, making antiviral therapy

unnecessary, affords the physician the possibility of temporizing before

beginning treatment, thereby avoiding the adverse effects of present drugs.[10]

The question would then be one of how long to wait before beginning therapy.

Systematic exploration of new protocols to obtain better information on

management of acute hepatitis C is limited by the paucity of cases for

study.[11] Prior to 1991, when blood donor screening for antibody to HCV

(anti-HCV) began, the full clinical range of early infections could be evaluated

by following transfusion recipients prospectively. At present, however, this

complication of blood administration has almost disappeared because of donor

screening for anti-HCV and HCV RNA.[12]

One opportunity to obtain further information about the course of HCV infection

is afforded by the National Heart, Lung, and Blood Institute's (NHLBI) having

retained the data and serial specimens from the Transfusion-transmitted Viruses

Study (TTVS) conducted from July 1974 through June 1980. We have recently

examined HCV-related events in 94 patients during the first 4 months after

acquiring the infection.[13] The present report utilizes the same group of

recipients to identify the circumstances of spontaneous resolution of viraemia.

In addition to TTVS observations, two of us (LBS and ZJB) directed another study

that was able to trace the late outcome (>10 years) for 27 of the 94 cases.[14]

FULL TEXT http://www.medscape.com/viewarticle/570152?src=mp & spon=20 & uac=31238BR

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