ACUTE HEPATITIS C: NATURAL COURSE AND RESPONSE TO ANTIVIRAL TREATMENT

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NATAP - www.natap.org

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AASLD

Dallas, Nov 9-13

Reported by Jules Levin

see NATAP website for ongoing AASLD reporting

Abstract 676. ACUTE HEPATITIS C: NATURAL COURSE AND

RESPONSE TO ANTIVIRAL TREATMENT

Tilman J Gerlach, Reinhart Zachoval, Norbert Gruener,

- 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; 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.

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