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Should Acute HCV Be Treated?
Although a German study found 98% of patients with acute HCV achieved response to interferon, there are good reasons to consider for not treating acute infection or to delay it. Read on for discussion about this and related study findings.
If a person can be identified with acute HCV, such as a health professional needle-stick, treatment should be considered. The problem that comes up is that HCV may be spontaneously cleared without HCV therapy. If not treatment with peg interferon can be considered. But, about 15-20% of exposed individuals may clear HCV spontaneously within 6 months. So do you treat or not, because side effects & toxicity are so burdensome & their is a percentage risk for morbidity. A recent published article suggested waiting perhaps 1 month to see if person clears HCV spontaneously. Individuals may clear HCV after 1 month but studies finding success in treating acute HCV initiate therapy within perhaps 6 months or less. The study results published in Hepatology are reported below from the German study results which is linked to below the rate of achieving a sustained response is close to 100%. This study was able to achieve such high rates of undetectability with IFN monotherapy. But there is no official policy on treating acute infection and follow-up studies are I think being conducted. Generally, however, it is very difficult to identify acute HCV infection just as in HIV, except in the case of a needle-stick by a health care worker. There are some controversies surrounding treatment during acute infection. The German study suggests treatment early on after infection may be crucial to achieving a high response rate. But in balancing the consideration that spontaneous clearance may occur and additional factors the decision to treat in acute infection is not an easy one.
Following exposure through needle-stick has been estimated to be 2%, but I think this may vary based on the viral load. The exposed individual should be tested by HCV-antibody and viral load to see if they actually have HCV. Then treatment can be considered. But remember in HCV monoinfection only perhaps 20% of chronically infected individuals go on to severe complications. So do you want to treat individuals with the difficult to tolerate HCV therapy who may not ever get sick? Individuals with chronic HCV and genotype 2/3 have a 80-90% response rate, so perhaps this gives further support for not treating these individuals during acute infection and waiting to see if they spontaneously clear it or if their disease progresses.
Acute hepatitis C: To treat or not to treat?
"Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load" (Hepatology 2003;37:60-64.)
.....The results of this study indicate that repeated measurement of HCV concentration in serum is useful to identify patients with acute hepatitis C who will benefit from antiviral therapy. In contrast, serial ALT measurements within the first weeks of acute disease failed to discriminate patients with spontaneous viral clearance from those who developed chronic viremia. Based on this approach, antiviral therapy may only be necessary in a minority of patients who seek medical attendance because of an acute icteric hepatitis C. This does not support the conclusion of the recent German study that, in view of a 98% response rate, all patients with acute hepatitis C should receive IFN therapy as soon as the diagnosis is made.
Natural history of acute hepatitis C virus (HCV) infection is variable. Progression to chronic hepatitis occurs in 50% to 84% of cases.1-9 This variation can be partly explained by the mode of transmission of HCV, viral factors, and by the ability of the host to mount a strong T-cell response to eliminate the virus. Acute HCV infection generally has a mild course, most cases are asymptomatic, and fulminant hepatic failure is very rare. The long-term sequelae of chronic hepatitis are the subject of ongoing discussions. Carefully conducted epidemiologic studies in well-documented cases of acute hepatitis C indicate that disease follows a very mild course and that occurrence of cirrhosis within the first 25 years after infection is rare.
Treatment of chronic hepatitis C, especially in patients infected with genotype 1 or 4, is still unsatisfactory. Despite improvements in response rates, current combination therapy with pegylated interferon (IFN) alfa-2a or -2b and ribavirin for chronic hepatitis C infection yields response rates from 54% to 56%. Prevention of chronicity by early antiviral treatment thus may be important. Because of the infrequent nature of acute hepatitis C the impact of early antiviral therapy has not been well studied and is conflicting.14 Only in 2 of 6 controlled trials using 3 MU IFN-2b 3 times a week for 6 to 24 weeks15 eradication of HCV RNA was assessed. In general, transition to chronicity was not different from untreated controls. Only one study using 10 MU of IFN-2b until normalization of transaminase levels reported an 82% sustained virologic response. A recent study using 5 MU IFN alfa-2b for 6 months showed a 98% HCV eradication in patients who received the full course of treatment. Based on these findings, the investigators concluded that early treatment with IFN-2b should be given to all patients with acute HCV infection.
Early interferon (IFN) therapy prevents viral persistence in acute hepatitis C, but in view of the resulting costs and morbidity patients who really need therapy have to be identified. Twelve consecutive patients with acute hepatitis C (9 women, 3 men, mean age: 39.5 18.8 y, genotype 1: 7, genotype 3a: 3, 2 could not be genotyped) were studied. The sources of infection were medical procedures in 6, sexual transmission in 3, and intravenous drug abuse in 3 patients. Viral load was measured by Cobas Amplicor HCV Monitor v2.0 (Roche Diagnostic Systems, Branchburg, NY). The time from infection to clinical symptoms was 43.3 8.6 (mean SD) days. Eight patients cleared hepatitis C virus (HCV) spontaneously and remained HCV-RNA negative with a follow-up of 9.0 3.9 months. In these patients viral load declined fast and continuously. The time from exposure to HCV-RNA negativity was 77.4 25.3 and from the first symptoms was 34.7 22.1 days. In 4 patients HCV-RNA levels remained high or even increased. Two of them became sustained responders to treatment initiated after a 6-week observation period. The 2 remaining patients were not treated (one because of contraindications for IFN, the other declined therapy) and are still HCV-RNA positive. In conclusion, patients with acute icteric hepatitis C have a high rate of spontaneous viral clearance within the first month after the onset of symptoms. IFN therapy appears only needed in patients who fail to clear the virus within 35 days after onset of symptoms. By this approach, IFN therapy was not necessary in two thirds of patients with acute hepatitis C.
Despite the impressive results from the German study there are still a number of important unresolved issues concerning the treatment of acute HCV infection. It remains unclear whether IFN should be given to all patients with acute hepatitis C on the basis of a single, uncontrolled trial. IFN therapy is expensive and carries a substantial morbidity. For example, one could consider not treating patients with genotype 2 or 3 because these patients can be cured in almost 90% of cases by combination therapy with pegylated IFN- and ribavirin if they become chronic. Furthermore, the rate of spontaneous viral clearance in symptomatic acute hepatitis C is unknown. In a recent report, 9 of 15 patients spontaneously eliminated HCV.18 Interestingly, in 3 of the patients HCV clearance occurred as late as 8 to 24 months after infection. A preliminary report has shown that 23 of 50 patients with acute hepatitis C clear the virus within the first 12 weeks, and IFN treatment initiated after 12 weeks from clinical presentation still achieved a 90% sustained virologic response. These findings would suggest that it is prudent to wait until 12 weeks and then consider treatment. However, it is unknown if a later initiation of therapy will yield the same favorable response rate as very early treatment. Thus, it may be unethical to wait 12 weeks when knowing that nearly all patients could be cured with immediate therapy. A way to solve this conflicting issue is to study factors predicting spontaneous viral eradication. In the present study we addressed this question by prospectively investigating HCV viremia in patients with acute hepatitis C.
Our data may not be applicable to all cases of acute hepatitis C. All patients in this study were symptomatic and the majority were women. By chance, 11 of the 12 patients were either tested for HCV within 3 months before onset of jaundice or a blood sample obtained during this period was available for testing. Thus, all cases but one were documented anti-HCV negative before exposure to HCV and had unquestionable acute hepatitis. Jaundice reflects an effective elimination of all infected hepatocytes by an appropriate cell-mediated immune mechanism.6 Thus, the presence of jaundice may identify a group of immune-competent subjects with a more favorable outcome than patients with asymptomatic acute hepatitis C. It is conceivable that asymptomatic cases with only mild elevation of ALT levels may develop viral persistence due to a weak initial immune response to viral antigens. It is unknown whether sex affects immune response to HCV. However, there are several lines of evidence that women may clear HCV easier than men. First, female gender is a good prognostic factor in IFN-based treatments of chronic hepatitis C. Second, chronic hepatitis C is more common in men than in women. In all treatment studies in Austria the men to women ratio was about 3:1. This difference may be due to a higher prevalence in risk behavior in men but more likely reflects a less effective immune clearance of HCV. Finally, the situation is quite similar in hepatitis B virus infection.26
There is no standard therapy for acute HCV infection. Several studies have evaluated the efficacy of IFN therapy for acute HCV infection. However, all studies have substantial limitations. The small number of patients (also in the present study) reflects the rarity of the disease. Some studies included primarily patients with asymptomatic transfusion-associated acute HCV infection. Treatment protocols were different with respect to the dose and duration of therapy. Some studies used IFN . More importantly, older studies measured outcome not on the basis of viral parameters but by the normalization of ALT levels. An unknown variable is the time of initiation of therapy with respect to the onset of symptoms or the time of infection. In the German study, the time from exposure to treatment was 89 days (mean, with a range of 30-112 d). In the present study, the mean time from infection to spontaneous viral clearance was 77 25 days Thus, the majority of the patients in the German study still had the propensity to achieve a spontaneous viral clearance.
In summary, these preliminary data indicate that patients with symptomatic acute hepatitis C may not need immediate antiviral therapy. Our data suggest that a follow-up of at least 30 days is required to identify those patients who should receive treatment. The role of early antiviral therapy in acute hepatitis C should be investigated by a prospective multicenter study that should include only patients who do not clear the virus spontaneously.
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