The Course of Hepatitis C Viraemia in Transfusion Recipients
The Course of Hepatitis C Viraemia in Transfusion Recipients
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.
Hepatitis C virus (HCV) infection is characterized by a high frequency of progression to chronic liver disease. 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. 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. In contrast, studies of acute hepatitis C show a sustained response to antiviral treatment of 80 to 98%. A recent study having an overall clearance rate of 71% showed its subpopulation with good protocol adherence to have a level of 89%.
Unfortunately, the presently available antiviral drugs usually have debilitating physical and emotional effects that can be very devastating. 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. 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. 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.
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. 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.
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.
Hepatitis C virus (HCV) infection is characterized by a high frequency of progression to chronic liver disease. 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. 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. In contrast, studies of acute hepatitis C show a sustained response to antiviral treatment of 80 to 98%. A recent study having an overall clearance rate of 71% showed its subpopulation with good protocol adherence to have a level of 89%.
Unfortunately, the presently available antiviral drugs usually have debilitating physical and emotional effects that can be very devastating. 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. 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. 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.
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. 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.