icon_folder.gif   Conference Reports for NATAP  
 
  AASLD ( American Association for the Study of Liver Diseases)
 
November 9-13, 2001, Dallas
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Abstract 676. ACUTE HEPATITIS C: NATURAL COURSE AND RESPONSE TO ANTIVIRAL TREATMENT
 
  Tilman J Gerlach, Reinhart Zachoval, Norbert Gruener, Maria-Christina Jung, Klinikum Grosshadern Med Dept II, Muenchen Germany; Axel Ulsenheimer, Winfried Schraut, Inst fuer Immunologie, Muenchen Germany; Albrecht Schirren, Klinikum Grosshadern Med Dept II, Muenchen Germany; Martin Waechtler, Markus Backmund, Gen Hosp München Schwabing, Muenchen Germany; Helmut Diepolder, Gerd Pape, Klinikum Grosshadern Med Dept II, Muenchen Germany
 
Below is the program book abstract, which I think portrays the essence of the oral presentation at the AASLD meeting. Another report on this presentation is being prepared. As you may know, German researchers first reported on treating acute HCV at DDW in the Spring 2001. A published article followed by much attention occurred in the Fall 2001. Identifying persons with acute HCV is very difficult just as it is in identifying acutely infected persons with HIV. But, if such a person can be identified treatment consideration may be crucial. Identification & treatment of acutely infected persons can be an important public policy position. This may have particular application to health care workers.
 
Background: Although screening of blood products for hepatitis C virus (HCV) has virtually eliminated post-transfusion hepatitis C, HCV still causes about 20% of cases of acute hepatitis today. These patients frequently present with acute symptomatic hepatitis C, which differs in many aspects from patients with post-transfusion hepatitis C. Little is known, however, about the natural course and the optimal treatment strategy for acute hepatitis C as it presents today.
 
Methods: The diagnosis of a HCV in fifty-six consecutive patients was based on seroconversion to anti-HCV antibodies or clinical and biochemical criteria (acute onset of hepatitis with elevation of ALT at least 10x the upper limit of normal, exclusion of other liver diseases) and on the presence of HCV-RNA by RT-PCR in the first serum sample.
 
Results: Fifty-six consecutive patients with acute hepatitis C were diagnosed in two large referral centers for infectious diseases and hepatology. 47/56 patients presented with symptomatic disease (fatigue (24%), abdominal pain (14%), jaundice (24%), nausea (19%)) while 9/56 were clinically asymptomatic. The major risk factors for acute HCV infection were IV-drug abuse (n=14), recent medical procedures (n=17), HCV-positive sexual partner (n=5), and needle-stick injury in medical employees (n=5), in 15 patients (27%) no risk factor or possible source of infection could be identified. Six patients received immediate antiviral therapy (IFN-a alone or in combination with ribavirin), 10 patients refused to therapy or were not eligable for IFN-a therapy. In 50 patients, not being treated immediately, the natural course of acute HCV was further studied: 34/50 (68%) patients initially cleared the virus spontaneously within a median of 11,9 weeks (range 2 to 24 weeks), but only twenty-three (47%) persistently remained HCV-RNA negative until the end of follow-up (median 23months, range 6 to 55 months) and were classified as self-limited hepatitis C. In eleven patients (22%) HCV RNA relapsed after a median of 23 weeks (range 8-86 weeks) and 16/50 (32%) patients did not clear HCV infection spontaneously and developed chronic hepatitis C. Patients with self-limited hepatitis C (n=22) and those developing chronic hepatitis C (n=28) did not differ with regard to age, risk factors for HCV infection, HCV-genotype, or initial viral load. However, symptomatic disease, female sex, and a high peak bilirubin level were strong predictors of spontaneous HCV clearance. While 49% of patients with symptomatic acute HCV cleared infection spontaneously, none of the patients with asymptomatic acute HCV (n=9) cleared HCV infection without treatment.
 
Since the majority (86%) of patients with spontaneous viral clearance lost HCV RNA within twelve weeks after onset of symptoms, antiviral therapy was recommended to patients who did not loose HCV RNA by week 12 after onset of symptoms. Of 34 patients with chronic hepatitis C, 24 patients started either interferon-alpha alone or in combination with ribavirin. So far, twenty-one patients responded with loss of HCV-RNA and normalization of aminotransferases; 15 of 16 IFN-responders who have completed follow-up (>6 months after end of treatment) are sustained responders and one patient relapsed. Five responders are still under follow-up (end-of-follow-up sustained response rate 82%) and three patients did not respond to antiviral therapy. Although not mentioned in the results but discussed in the oral presentation was the 6 patients who were treated immediately upon identification. And I recall 4 or 5 of them had a virologic response.
 
Conclusions: In the management of acute HCV infection a high spontaneous viral clearance rate within the first twelve weeks after onset of symptoms has to be considered. The strategy to treat symptomatic patients who remained HCV-RNA positive beyond three months after onset of disease led to an overall sustained viral clearance in 90% of patients, while unnecessary treatment was avoided in those with spontaneous viral clearance. In contrast patients with asymptomatic acute HCV infection are unlikely to clear the virus spontaneously and antiviral therapy should be commenced as early as possible.