Zusammenfassung
Einleitung: Der Verlauf viraler Hepatitiden ist interindividuell sehr unterschiedlich und reicht von asymptomatischen Erkrankungen bis hin zum Leberversagen. Nur wenige Daten liegen bislang über Geschlechtsunterschiede bei Patienten mit Lebertransplantation (OLT) vor. Wir haben die Geschlechtsverteilung bei Patienten untersucht, die aufgrund einer Virushepatitis lebertransplantiert wurden. Methoden: Eine retrospektive Analyse wurde bei einer Kohorte von 368 Patienten durchgeführt, die bei Virushepatitis und akutem oder chronischem Leberversagen lebertransplantiert wurden. In 96 von ihnen lag zum Zeitpunkt der OLT noch ein hepatozelluläres Karzinom (HCC) vor. Die Geschlechtsverhältnisse der verschiedenen Hepatitis-Virusinfektionen sowie in Bezug zum HCC wurden analysiert. Ergebnisse: Signifikant mehr Männer als Frauen wurden für eine chronische Hepatitis B lebertransplantiert. Im Gegensatz dazu waren Patienten nach OLT bei einer fulminanten Hepatitis B häufiger weiblichen Geschlechts. Bei Patienten, die für eine chronische HCV- or HDV-Infektion transplantiert wurden, zeigten sich keine signifikanten Geschlechtsunterschiede. Allerdings fand sich bei Männern in diesen beiden Gruppen chronischer Lebererkrankungen häufiger ein HCC. Schlussfolgerung: Bei lebertransplantierten Patienten mit Hepatitis-B-Infektion zeigten sich deutliche Geschlechtsunterschiede, da mehr Frauen an fulminantem Verlauf der akuten HBV transplantiert wurden, während mehr Männer bei chronischer HBV im Endstadium transplantiert wurden. Die Rolle des Geschlechts bei chronischer HCV- und HDV-Infektion war weniger deutlich außer einem männlichen Übergewicht bei Patienten mit HCC.
Abstract
Introduction: The course of viral hepatitis shows wide interindividual differences, ranging from asymptomatic disease to liver failure. Only limited data on gender differences in patients undergoing liver transplantation (OLT) exist. We studied the gender distribution in patients who underwent liver transplantation for viral hepatitis. Methods: A retrospective analysis was performed on a cohort of 368 patients who underwent OLT for viral hepatitis-associated acute or chronic liver failure. In 96 of them, additional hepatocellular carcinoma (HCC) was present at transplantation. Gender ratios of the different hepatitis virus infections and in relation to HCC were evaluated. Results: Significantly more males than females underwent OLT for chronic HBV. In contrast, patients after OLT for fulminant HBV were more frequently females. In patients transplanted for chronic HCV or HDV, no significant gender differences were found. However, men presented more frequently with HCC in both groups of chronic liver disease. Conclusions: There was a gender difference in HBV infection with more women developing fulminant hepatic failure in acute HBV while more men progressed to end-stage liver disease in chronic HBV. The role of gender in chronic HCV and HDV infection was less pronounced, except for a male predominance among patients with HCC.
Schlüsselwörter
Leber - Hepatitis B - Hepatitis C - Hepatitis D - Virushepatitis
Key words
liver - hepatitis B - hepatitis C - hepatitis D - viral hepatitis
References
1
Owens I PF.
Sex differences in mortality rate.
Science.
2002;
297
2008-2009
2
Whitacre C C.
Sex differences in autoimmune disease.
Nature Immunol.
2001;
2
777-780
3
The Global Burden Of Hepatitis C Working Group .
Global burden of disease (GBD) for hepatitis C.
J Clin Pharmacol.
2004;
44
20-29
4 http://www.who.int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf
5
Kenny-Walsh E.
Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.
N Engl J Med.
1999;
340
1228-1233
6
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
7
Ferenci P, Ferenci S, Datz C et al.
Morbidity and mortality in paid Austrian plasma donors infected with hepatitis C at plasma donation in the 1970 s.
J Hepatol.
2007;
47
31-36
8
Tillmann H L, Heiken H, Knapik-Botor A et al.
Infection with GB virus C and reduced mortality among HIV-infected patients.
N Engl J Med.
2001;
345
715-724
9
Rehermann B, Seifert U, Tillmann H L et al.
Serological pattern of hepatitis C virus recurrence after liver transplantation.
J Hepatol.
1996;
24
15-20
10
Tillmann H L, Hadem J, Leifeld L et al.
Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.
J Viral Hep.
2006;
13
256-263
11
Thierfelder W, Hellenbrand W, Meisel H et al.
Prevalence of markers for hepatitis A, B and C in the German population. Results of the German National Health Interview and Examination Survey 1998.
Eur J Epidemiol.
2001;
17
429-435
12
Fattovich G.
Natural history of hepatitis B.
Journal of Hepatology.
2003;
39
S50-S58
13
Alward W LM, McMahon B J, Hall D B et al.
The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma.
J Infect Dis.
1985;
151
604-609
14
Lok A SF, Lai C L, Wu P C et al.
Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection.
Gastroenterology.
1987;
92
1839-1843
15
McMahon B J, Holck P, Bulkow L et al.
Serologic and clinical outcomes of 1536 Alaska natives chronically infected with hepatitis B virus.
Ann Intern Med.
2001;
135
759-768
16
Chu C M, Sheen I S, Lin S M et al.
Sex difference in chronic hepatitis B virus infection: studies of serum HbeAg and alanine aminotransferase levels in 10,431 asymptomatic Chinese HbsAg carriers.
Clin Infect Dis.
1993;
16
709-713
17
London W T, Drew J S.
Sex differences in response to hepatitis B infection among patients receiving chronic dialysis treatment.
Proc Natl Acad Sci USA.
1977;
74
2561-2563
18
Robert Koch-Institut. .
Epidemiologisches Bulletin.
2005 (46);
421-429
19
Poynard T, Mathurin P, Lai C L et al.
PANFIBROSIS Group. A comparison of fibrosis progression in chronic liver diseases.
J Hepatol.
2003;
38
257-265
20
Fattovich G, Pantalena M, Zagni I et al.
Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients.
Am J Gastroenterol.
2002;
97
2886-2895
21
Kim W R, Ishitani M R, Dickson E R.
Rising burden of Hepatitis B in the United States should ‘the other’ virus be forgotten?.
Hepatology.
2002;
36 (S2)
222A
22
Jilg W, Hottentrager B, Weinberger K et al.
Prevalence of markers of hepatitis B in the adult German population.
J Med Virol.
2001;
63
96-102
23
Verthelyi D.
Sex hormones as immunomodulators in health and disease.
Int Immunopharmacol.
2001;
1
983-993
24
Palitzsch K D, Hottentrager B, Schlottmann K et al.
Prevalence of antibodies against hepatitis C virus in the adult German population.
Eur J Gastroenterol Hepatol.
1999;
11
1215-1220
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
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
27
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
28
Wright M, Goldin R, Fabre A et al.
Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.
Gut.
2003;
52
574-579
29
Di Martino V, Lebray P, Myers R P et al.
Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure.
Hepatology.
2004;
40
1426-1433
30
Codes L, Asselah T, Cazals-Hatem D et al.
Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy.
Gut.
2007;
56
390-395
31
Lacort M, Leal A M, Liza M et al.
Protective effect of estrogens and catecholestrogens against peroxidative membrane damage in vitro.
Lipids.
1995;
30
141-146
32
Yasuda M, Shimizu I, Shiba M et al.
Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats.
Hepatology.
1999;
29
719-727
33
Omoya T, Shimizu I, Zhou Y et al.
Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress.
Liver.
2001;
21
183-191
34
Ishikawa T, Ichida T, Yamagiwa S et al.
High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis.
J Gastroenterol Hepatol.
2001;
16
1274-1281
35
Lee C M, Lu S N, Changchien C S et al.
Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection.
Cancer.
1999;
86
1143-1150
36
Tangkijvanich P, Mahachai V, Suwangool P et al.
Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma.
World J Gastroenterol.
2004;
10
1547-1550
37
Lam C M, Yong J L, Chan A O et al.
Better survival in female patients with hepatocellular carcinoma: oral contraceptive pills related?.
J Clin Gastroenterol.
2005;
39
533-539
38
Naugler W E, Sakurai T, Kim S et al.
Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.
Science.
2007;
317
121-124
39
Yu M W, Yang Y C, Yang S Y et al.
Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men.
J Natl Cancer Inst.
2001;
93
1644-1651
40
Yu M W, Cheng S W, Lin M W et al.
Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma.
J Natl Cancer Inst.
2000;
92
2023-2028
41
Ma W L, Hsu C L, Wu M H et al.
Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma.
Gastroenterology.
2008;
135
947-955
42
Chiu C M, Yeh S H, Chen P J et al.
Hepatitis B virus X protein enhances androgen receptorresponsive gene expression depending on androgen level.
Proc Natl Acad Sci USA.
2007;
104
2571-2578
43
Yang W J, Chang C J, Yeh S H et al.
Hepatitis B virus X protein enhances the transcriptional activity of the androgen receptor through c-Src and glycogen synthase kinase-3 kinase pathways.
Hepatology.
2009;
49
1515-1524
44
Wang A G, Moon H B, Lee M R et al.
Gender-dependent hepatic alterations in H-ras12V transgenic mice.
J Hepatol.
2005;
43
836-844
Prof. Dr. Hans L. Tillmann
Duke Clinical Research Institute
2400 Pratt Street
Durham
NC 27705
USA
Phone: ++ 1/9 19/6 68 46 20
Fax: ++ 1/9 19/6 68 71 64
Email: hans.tillmann@duke.edu