Zusammenfassung
Der Einfluss von Viruslast, HCV-Genotyp, Alter, Geschlecht und Body-Mass-Index (BMI)
auf den klinischen Verlauf einer akuten Hepatitis-C-Virusinfektion ist bis heute weitestgehend
unbekannt. Wir untersuchten den Einfluss dieser Faktoren an einem Kollektiv von 259
Patienten mit akuter Hepatitis-C-Virusinfektion. Die Patienten wurden zwischen 1998
und 2008 in die Datenbank des Kompetenznetzes Hepatitis eingeschlossen. Bei 171 Patienten
(66 %) wurde innerhalb von 4 Monaten nach der Diagnosestellung eine antivirale Therapie
mit Interferon-alpha begonnen. Nach der Analyse der Daten zeigten sich folgende Ergebnisse:
1. der Infektionsweg war mit dem Alter assoziiert; Patienten mit i. v. Drogenkonsum
waren signifikant jünger als Patienten ohne i. v. Drogenkonsum, während hingegen die
Anzahl der Patienten, die im Rahmen medizinischer Engriffe infiziert wurden, mit zunehmendem
Alter anstieg; 2. Patienten jünger als 30 Jahre waren häufiger mit dem HCV-Genotyp
3 infiziert (26 versus 8 % für Patienten älter als 50 Jahre; p = 0.03); 3. 51 %
der Patienten hatten einen Ikterus zum Zeitpunkt der Diagnosestellung und 28 % hatten
eine 30-fache Erhöhung der Transaminasen, jedoch zeigte keiner der Patienten Zeichen
eines akuten Leberversagens; 4. der HCV-Genotyp war nicht assoziiert mit der Schwere
der Erkrankung und auch ebenfalls nicht assoziiert mit der Länge des Zeitraums zwischen
dem Infektionszeitpunkt und dem Beginn der Symptome; 5. eine niedrige Viruslast war
assoziiert mit niedrigerer AST und einem verlängerten Zeitraum zwischen Infektionszeitpunkt
und dem Einsetzten der Symptome; die Schwere der Erkrankung zeigte jedoch keine Korrelation
mit dem Infektionsweg, dem Alter, dem Geschlecht und BMI. Insgesamt zeigte sich bei
dem größten Teil der Patienten in unserer Kohorte ein relativ milder Verlauf der Erkrankung.
Die Schwere der Erkrankung war nicht assoziiert mit dem HCV-Genotyp, der Viruslast,
dem Alter, dem Geschlecht und dem BMI.
Abstract
Introduction: The impacts of viral load, genotype, age, sex and BMI on the clinical course of acute
hepatitis C are poorly defined. Here we studied 259 patients with acute HCV infection
recruited in the German Hep-Net data base between 1998 and 2008. Antiviral treatment
with interferon alpha was initiated in 171 patients (66 %) within 4 months after the
diagnosis of acute hepatitis C. Results: In this cohort (i) the mode of infection was associated with age as iv-drug users
were significantly younger than non-iv-drug users while the proportion of patients
who acquired HCV by medical procedures increased with age; (ii) patients younger than
30 years were more often infected with genotype 3 (26 % versus 8 % for patients older
than 50 years; p = 0.03); (iii) 51 % of patients were icteric and 28 % presented
with a 30-fold elevation of liver enzymes, however, no fulminant hepatic failure occurred;
(iv) HCV genotype was not associated with disease severity and time to onset of symptoms;
(v) low HCV viremia was associated with lower serum AST levels and a longer time from
exposure to onset of symptoms; (vi) disease severity was independent from the mode
of infection, age, sex and body mass index (BMI). Conclusions: In this large cohort of patients admitted for antiviral therapy, acute hepatitis
C took a rather mild course of disease in the majority of patients. Disease severity
was not associated with HCV genotype, viral load, age, sex and BMI.
Schlüsselwörter
Virushepatitis - Leber - Hepatitis C
Key words
viral hepatitis - liver - hepatitis C
References
1
Alter M J.
Prevention of spread of hepatitis C.
Hepatology.
2002;
36
S93-S98
2
Prati D.
Transmission of hepatitis C virus by blood transfusions and other medical procedures:
a global review.
J Hepatol.
2006;
45
607-616
3
Marti Nez-Bauer E, Forns X, Armelles M. et al .
Hospital admission is a relevant source of hepatitis C virus acquisition in Spain.
J Hepatol.
2008;
48
20-27
4
Santantonio T, Medda E, Ferrari C. et al .
Risk factors and outcome among a large patient cohort with community-acquired acute
hepatitis C in Italy.
Clin Infect Dis.
2006;
43
1154-1159
5
Deterding K, Wiegand J, Gruner N. et al .
Medical procedures as a risk factor for HCV infection in developed countries: do we
neglect a significant problem in medical care?.
J Hepatol.
2008;
48
1019-1020
6
Kubitschke A, Bader C, Tillmann H L. et al .
Injuries from needles contaminated with hepatitis C virus: how high is the risk of
seroconversion for medical personnel really?.
Internist.
2007;
48
1165-1172
7
Santantonio T, Wiegand J, Tilman G J.
Acute hepatitis C: Current status and remaining challenges.
J Hepatol.
2008;
49
625-633
8
Gerlach J T, Diepolder H M, Zachoval R. et al .
Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance.
Gastroenterology.
2003;
125
80-88
9
Corey K E, Ross A S, Wurcel A. et al .
Outcomes and treatment of acute hepatitis C virus infection in a United States population.
Clin Gastroenterol Hepatol.
2006;
4
1278-1282
10
Mosley J W, Operskalski E A, Tobler L H. et al .
Viral and host factors in early hepatitis C virus infection.
Hepatology.
2005;
42
86-92
11
Cox A L, Netski D M, Mosbruger T. et al .
Prospective evaluation of community-acquired acute-phase hepatitis C virus infection.
Clin Infect Dis.
2005;
40
951-958
12
Jauncey M, Micallef J M, Gilmour S. et al .
Clearance of hepatitis C virus after newly acquired infection in injection drug users.
J Infect Dis.
2004;
190
1270-1274
13
Wang C C, Krantz E, Klarquist J. et al .
Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing
viral clearance.
J Infect Dis.
2007;
196
1474-1482
14
Bakr I, Rekacewicz C, El Hosseiny M. et al .
Higher clearance of hepatitis C virus infection in females compared with males.
Gut.
2006;
55
1183-1187
15
Mosley J W, Operskalski E A, Tobler L H. et al .
The course of hepatitis C viraemia in transfusion recipients prior to availability
of antiviral therapy.
J Viral Hepat.
2008;
15
120-128
16
Wiegand J, Buggisch P, Boecher W. et al .
Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection:
the HEP-NET acute-HCV-II study.
Hepatology.
2006;
43
250-256
17
Wiese M, Grungreiff K, Guthoff W. et al .
Outcome in a hepatitis C (genotype 1b) single source outbreak in Germany – a 25-year
multicenter study.
J Hepatol.
2005;
43
590-598
18
De Rosa F G, Bargiacchi O, Audagnotto S. et al .
Twelve-week treatment of acute hepatitis C virus with pegylated interferon-alpha-2b
in injection drug users.
Clin Infect Dis.
2007;
45
583-588
19
Broers B, Helbling B, Francois A. et al .
Barriers to interferon-alpha therapy are higher in intravenous drug users than in
other patients with acute hepatitis C.
J Hepatol.
2005;
42
323-328
20
Cox A L, Netski D M, Mosbruger T. et al .
Prospective evaluation of community-acquired acute-phase hepatitis C virus infection.
Clin Infect Dis.
2005;
40
951-958
21
Seeff L B, Hollinger F B, Alter H J. et al .
Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type
C hepatitis: A national heart, lung, and blood institute collaborative study.
Hepatology.
2001;
33
455-463
22
Alter M J, Margolis H S, Krawczynski K. et al .
The natural history of community-acquired hepatitis C in the United States. The Sentinel
Counties Chronic non-A, non-B Hepatitis Study Team.
N Engl J Med.
1992;
327
1899-1905
23
Ostapowicz G, Fontana R J, Schiodt F V. et al .
Results of a prospective study of acute liver failure at 17 tertiary care centers
in the United States.
Ann Intern Med.
2002;
137
947-954
24
Farci P, Alter H J, Shimoda A. et al .
Hepatitis C virus-associated fulminant hepatic failure.
N Engl J Med.
1996;
335
631-634
25
Jaeckel E, Cornberg M, Wedemeyer H. et al .
Treatment of acute hepatitis C with interferon alfa-2b.
N Engl J Med.
2001;
345
1452-1457
26
Manns M P, Meyer S, Wedemeyer H.
The German network of excellence for viral hepatitis (Hep-Net).
Hepatology.
2003;
38
543-544
27
Wedemeyer H, Pethig K, Wagner D. et al .
Long-term outcome of chronic hepatitis B in heart transplant recipients.
Transplantation.
1998;
66
1347-1353
28
Farci P, Alter H J, Shimoda A. et al .
Hepatitis C virus-associated fulminant hepatic failure.
N Engl J Med.
1996;
335
631-634
29
Wedemeyer H, Jackel E, Wiegand J. et al .
Whom? When? How? Another piece of evidence for early treatment of acute hepatitis
C.
Hepatology.
2004;
39
1201-1203
30
Jauncey M, Micallef J M, Gilmour S. et al .
Clearance of hepatitis C virus after newly acquired infection in injection drug users.
J Infect Dis.
2004;
190
1270-1274
31
Cox A L, Netski D M, Mosbruger T. et al .
Prospective evaluation of community-acquired acute-phase hepatitis C virus infection.
Clin Infect Dis.
2005;
40
951-958
32
Bakr I, Rekacewicz C, El Hosseiny M. et al .
Higher clearance of hepatitis C virus infection in females compared with males.
Gut.
2006;
55
1183-1187
33
Wang C C, Krantz E, Klarquist J. et al .
Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing
viral clearance.
J Infect Dis.
2007;
196
1474-1482
34
Mosley J W, Operskalski E A, Tobler L H. et al .
The course of hepatitis C viraemia in transfusion recipients prior to availability
of antiviral therapy.
J Viral Hepat.
2008;
15
120-128
35
Diehl A M.
Hepatic complications of obesity.
Gastroenterol Clin North Am.
2005;
34
45-61
36
Lehmann M, Meyer M F, Monazahian M. et al .
High rate of spontaneous clearance of acute hepatitis C virus genotype 3 infection.
J Med Virol.
2004;
73
387-391
37
Hofer H, Watkins-Riedel T, Janata O. et al .
Spontaneous viral clearance in patients with acute hepatitis C can be predicted by
repeated measurements of serum viral load.
Hepatology.
2003;
37
60-64
38
Brouard C, Pradat P, Delarocque-Astagneau E. et al .
Epidemiological characteristics and medical follow-up of 61 patients with acute hepatitis
C identified through the hepatitis C surveillance system in France.
Epidemiol Infect.
2008;
136
988-996
39
Esteban J I, Sauleda S, Quer J.
The changing epidemiology of hepatitis C virus infection in Europe.
J Hepatol.
2008;
48
148-162
40
Heller T, Rehermann B.
Acute hepatitis C: a multifaceted disease.
Semin Liver Dis.
2005;
25
7-17
41
Mondelli M U, Cerino A, Cividini A.
Acute hepatitis C: diagnosis and management.
J Hepatol.
2005;
42 (Suppl)
S108-S114
42
Wang C C, Krantz E, Klarquist J. et al .
Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing
viral clearance.
J Infect Dis.
2007;
196
1474-1482
43
Roy K, Hay G, Andragetti R. et al .
Monitoring hepatitis C virus infection among injecting drug users in the European
Union: a review of the literature.
Epidemiol Infect.
2002;
129
577-585
44
Aceijas C, Rhodes T.
Global estimates of prevalence of HCV infection among injecting drug users.
Int J Drug Policy.
2007;
18
352-358
45
Mihm S, Fayyazi A, Hartmann H. et al .
Analysis of histopathological manifestations of chronic hepatitis C virus infection
with respect to virus genotype.
Hepatology.
1997;
25
735-739
46
Ross R S, Viazov S, Renzing-Kohler K. et al .
Changes in the epidemiology of hepatitis C infection in Germany: shift in the predominance
of hepatitis C subtypes.
J Med Virol.
2000;
60
122-125
47
Meyer M F, Lehmann M, Cornberg M. et al .
Clearance of low levels of HCV viremia in the absence of a strong adaptive immune
response.
Virol J.
2007;
4
58
48
Mizukoshi E, Eisenbach C, Edlin B R. et al .
Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users
frequently exposed to HCV.
J Infect Dis.
2008;
198
203-312
49
Ruys T A, Nanlohy N M, Berg C H. et al .
HCV-specific T-cell responses in injecting drug users: evidence for previous exposure
to HCV and a role for CD 4 + T cells focussing on nonstructural proteins in viral
clearance.
J Viral Hepat.
2008;
15
409-420
50
Tillmann H L, Hadem van den J, Leifeld L. et al .
Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis
B, a multicenter experience.
J Viral Hepat.
2006;
13
256-263
PD Dr. Heiner Wedemeyer
Gastroenterology, Hepatology and Endocrinology, Hannover Medical School
Carl-Neuberg-Str.1
30625 Hannover
Email: Wedemeyer.Heiner@mh-hannover.de