cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5orita mayu.pdf · gammopathy bc ˘ ˝˛œšˆ wx...

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臌腵腷腩腺腱腼膇臛膌膫膰 Vol. 32, pp. 453460, 2004 C 腐腚腕腍腓腌腂腙腀腆腉腅腇腊腈腉腋腑腔腏腃 M 腖腘腑腔腂腎腁腄腒腗 腆腚 腆腉 腃腇 腙腐 腗腒腈 腓腛腊 腋腌 腖腏 腓腛 腑腅 腔腖 膶臹 : 16 10 13 C 臈膏膳膎腚致腃腭腷腬腮腹腳腷腺膘膽腅腢腝 M 臜至膘膽腚膑腍腕膚自腨膤腓腑C 臈膏膳膎膎膴 183 臟腭腷腬腮腹腳腷腺臈腛膽91 50῎῍腖腁腓腑膏膢腚腅腊腥腭腷腬腮腹腳腷腺臈膏膀腢腤腡膥腆腓腑腍腆腍腙腇腣臷臂膑臎臢腙腘腛膽臀腇膛腣腦腑膽腜腙腉臮臜至臮臐膘腡腭腷腬腮腹腳腷腺腛腏腉腗腛膑腜臯腠腣腦腙腆腓腑腭腷腬腮腹腳腷腺腜腾臈腚臶膋腍腕膘臊 HCV RNA 腇膺腙 膘臊臙膄腛臤膂膘臊腷腫腵腯腪腰腽膮腛臔膅腇臯腠腣腦腑M 臜至膘膽腜腭腷腬腮 腹腳腷腺臈腛 2 4῎῍腾臈腛 1 5῎῍腚臯腠腣腦腑腭腷腬腮腹腳腷腺臈腛 2 腜腂 腏腦腡 IgM-k 膗腛 M 臜至腇膚膹腌腦腷腫腵腯腪腰腽膮腜臠腍腂膥臝腨膲腍腕腂腑腟腑腭腷腬腮腹腳腷腺膘膽腚膑腎腥膻膽臀腇臯腠腣腦腑腋腦腣腛膚自腆腣C 臈膏膳膎 腚腅腂腕腭腷腬腮腹腳腷腺膘膽腜膥臸臨腚臯腠腣腦腥腋腗腇臵腍腑腟腑腭腷腬腮腹腳腷 腚腅腊腥 M 臜至膘膽腜腭腷腬腮腹腳腷腺腛膬臋腇膈膿腚膔腋腥膩腚膦臼腎腥膆臱 臈腇腁腥腗膣腄腣腦腑ῐῌ῏ C 臈膏膀膏膢膏膨腭腷腬腮腹腳腷腺M 臜至 C 臈膏膀腚腜臆腛膏膊膦臼膽腨致腃腋腗腇 臞腣腦腕腂腥 13臟腖腡腭腷腬腮腹腳腷腺膘膽腜臈臔臁臈膯膖臙臅膀腛膦臼腨致腃腋腗腡腁腤臒腉 腆腣臞腣腦腕腂腥膦臼膽腖腁腥 47C 臈膏膀腚腅腊腥腭腷腬腮腹腳腷腺膘膽腛膦臼腨腋腦 腟腖膧腍腕腈腑 8腍腆腍腙腇腣膏膢膏膨膒腗腂腓腑臄臥臈膏膳膎腚腅腊腥腭腷腬腮腹腳腷 腺腛膦臼腚膑腍腕腜膷臺腙膚自腜膤腧腦腕腂腙 C 臈膏膀腚腅腊腥腭腷腬腮腹腳腷腺膘膽腜膵腗腍腕 Brouet II 膗腚臗腎腥臖腒腷腫腵 腯腪腰腽膮膍臈腨腎腥腶腲腭腹腀腱腸 IgM 膟臙 腗腴腷腭腹腀腱腸 IgG 膟臙腨膡臉臉臺腚膱腔腋腗 腇腧腆腓腕腂腥 9, 10膸腓腕腭腷腬腮腹腳腷腺膘膽 膦臼 C 臈膏膀腛膽腛臟腚腜M 臜至膘膽腨 腎腥膽腇臘膪腍膻臓腨腎腥膆臱臈 腇腁腥腍腆腍腆腅腖腜腋腃腍腑膐臦腆腣腛膚自腜 腛臡腞腑膜腤膤腧腦腕腂腙腂腐腋腖C 臈膏膳膎膎膴腨臚膾腗腍腕腭腷腬 腮腹腳腷腺膘膽膕腝 M 臜至腛膦臼腚膑腎腥臑膝腈 膚自腨膤腓腑臌腵腷腩腺腱腼膇臛膌 臬膇膌膼膃膓膏臕臬膇453 37

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Page 1: Cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5Orita Mayu.pdf · Gammopathy bc ˘ ˝˛œšˆ WX ž ˘t 1 Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto

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Page 2: Cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5Orita Mayu.pdf · Gammopathy bc ˘ ˝˛œšˆ WX ž ˘t 1 Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto

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���������� ������ 2003������ C ��������� ���� !"�#$%�� C ��������#&'�()*+,#-.�� ��/���0 103 �� �1239�� �345 41�678� ���09�12!:;/� <= �>8?;@#�AB-.�11�� C�� �345!%D/EF%D��G��HIH!JK -.�� LM� NOPQ��0� ��RS�T�U!VW�/+,K XA��TYZ[\]^Y_ �EIA`�� HCV RNA���

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������� 183��o�pqr]����!��/ 91��50��67.�� ���0� �12� �12VW�3456!��/���� 36��103�� 37��� 67��39�� 26��� 68��41�� 28��67�� ����o�pqr]��b�!VW��K.�� ���� �129�12VW�345!�6/o�pqr]������#� LK.� �p�0.88��� �� ������������������� !"�� 2�o�pqr]�����9t��9!�6o�pqr]��b��¡¢�£¤¥#¦§�� ¨©� RSª#� ��/� ���� t��9«�LK.�� uv¬78A/b¬#� ���/� ���017��o�pqr]����­ 31 �� 5 �: 16��o�pqr]��t�­ 58 �� 10 �: 17��� �

12 24��o�pqr]����­ 25 �� 7 �:28�� o�pqr]��t�­ 12 �� 2 �: 17��� �345 32��o�pqr]���� 28��8�: 29�� o�pqr]��t�­ 13�� 6�:46��� 9®¯!��9°�uv¬�b¬!±²/³´�8µ)/�  ��«!!� o�pqr]��b�9!¶R/¥ �LK.��

Table 1. Prevalence of Cryoglobulinemia in Chronic

Hepatitis C

Table 2. Symptoms and Urinalysis of cryoglobulin-

positive and -negative Patients with Chronic

Hepatitis C

·=¸� ¹º»¼ 454

38

Page 3: Cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5Orita Mayu.pdf · Gammopathy bc ˘ ˝˛œšˆ WX ž ˘t 1 Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto

� ������������� �� C������������� 3������������� �� C ����������������� HCV-RNA � ����������!" 443�487 KIU�ml� �� 772�819 KIU�ml�#$� ��������� HCV RNA �%&'()�� *�� HCV +�,�- � ���������� ���- 1: 40 �77��� ���- 2: 12 �23��� ���������� ���- 1:42�86��� ���- 2: 7�14���#$� ��������� C �������+�,�-� �. /0%123'()��� ������������� ������������ 4������������� ��4546�7� 89:6;� ���<�=>?������ 4546��40 @AB�7 � ��������� 14��91C 13�� � 7��92C 6 ��#$� DE�.F GH23'()��I89:6J �CH50�20� KL � ��������� 32��91C 29�� � 18��92C 17�����������E�M()�� *�� ���<�=>?��50 AB� � ��������� 19��91 C 17 �� � 2��92 C 2 �����������E�M()��� ��M� ��!"#�� 5�MNO ��������� 4��50C2 �� ��������� 5��21 C 1�.GH23����������� 2 HCV+�,�- � PQ3R 2�#$� M� ���<�=>?�IgM ST'BU%GH23�� MNO 2�R IgM-k�#)�� VW� XYZ[ \]^_ GH23'()�� ` 1� ��������8`.abc'de� fgh6i�%GH23� ijk lmn o^_gh6i��MPGN� �#)�� ` 2 � ijk pq3rP'PR � 8s�/tu%GH23����������� 1 4546% 1280@�BU�rP�� MNO IgG-k �#)��

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��������8` C �f��.Lvwx�yLv` z{|}c'R �#x� �������� k~ � �������pq3x� �*� ��� C �f��.�z��������8` KL 30� (2 40� ��3rPx57, 10������ k�.�x�7 � f�� `.��wx� 36��#$� �3*� ������ ���#x������Z[��P)���.�Pr�������� �7%�P�� ��*� �� ¡T�#x%� C���¢`£¤¥�¦� ���������7 f���$IP��%§T�r�$8�� �� ¨`���������8`

Table 3. Hepatitis C Viral Markers in Cryoglobulin-

positive and -negative Patients with Chronic

Hepatitis C

Table 4. Immunological Markers in Cryoglobulin-

positive and -negative patients with Chronic

Hepatitis C

C�f�©ª���������«¬MNO8` 455

39

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������������� �������� ���������� C����������� Cold activation ���������� �!����"#$%&�����12�� Coldactivation �'()*+,(-./��0!���12 �313�� 45�6��78 CH50 �'()*+,(-�9 :;<=>���� >�>!� Cold activation �������������1?@ ��AB� �3� 4CDE� �����FGH�IJ���'()*+,(-�9��KL>M� �N�OP!Q��R/S<T>M/�!�UM� @M� �V������W.DX��M/�Y��� ��IJ>� �Z![\<=�!�UM� '()*+,(-�����V������].����^_��!�UMA���`a� C��9�bc�����'()*+,(-./� Subclinical ! �def ���`a��M�C���ghij�'()*+,(-���>��� ghij�'()*+,(-�9 k!���"lm���M� A��4@ ��n�o!�lm ��14�� p�qr�� ��� .s<����t� HCV<uvw'()*+,(-�x�yz��M{�9��� .s �!|}.<��Mghij��~�<�"A� ghij��'()*+,(-����!�����!� ��`a����C��9����"'()*+,(-./� ��II ��.s ������>��� ������`a�(g��h�r��;������ 6��/ (g��h�r��KL!���M� @

M� ��� Cold activation ��������.s����:�!���M� A���D��'()*+,(-./��?<�����"!���!�A��!��M�C��9����"'()*+,(-./��r�1?@ ��AB� � ��� '()*+,(-�e|� II��'()*+,(- �3� HCV,IgG '�j��('+��i HCV ��� IgM '�j���'+��i��<�������� IgM'�j���'+��i���(g��h�r��9<�>� C��9�������'()*+,(-<��# � � ��A���� p�¡¢£¤�7��¥ ��� Fornasieri ��� '()*+,(-�9 C��9��c��$¦. B(-§¨� C ���ghij�©ª>�«3� IgM-k ��(g��h�r�<¡¢��A�<=>�«315��C����'()*+,(-����¬0���A�%�>����IgM-k ��(g��h�r�e��¡¢��M­�� V� �&®¯' M-peak!����A������� °t� 1995(±)�|����n_���16�20�� A���e|�h²(³�� �3� C��9��c��« �MV�./����� 10�±K��n>���18, 19�� >�>p�x* C��9��c���MV�./����!���!�UM����n ��20��6��45�D+ � C ��9��c��« 

�MV�./���� 2�4���!���M� A�� 2 �(g��h�r�� IgM �´�!KL<�U�«3� M V�� IgM-k ��� µU�'()*+,(-����� �� monoclonal IgM´��[¶>M ��`a���� @MA�� 2

Table 5. Patients with Monoclonal Gammopathy

·,¸- ¹º»¼ �456

40

Page 5: Cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5Orita Mayu.pdf · Gammopathy bc ˘ ˝˛œšˆ WX ž ˘t 1 Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto

����������� ������������������ �������������� �!"���#$%��&�!"�������������'(��)*�+,�� t �12 : 14� �-./01�23 bcl-2 � Ig J�H�456�7�+� Monoclonal IgM #���� B89�:;<=>?#@�+�AAB����C��,D�21�25�� EFGHI� CJKFLM!���N�OPQ!���N�RS!"3� TU�V�WX�BD���,D�26�� Y � Z[� 2��!\GH!]^89�I_F`a�bc��,DBD� de C JKFLM��������C��,D�fF�gI�\� t �12 : 14� �bc��,h322�� ijkD�l�� 2���hm� HCV�� T���\n��o=p 2 �Genotype 2 �qr��� !"st� ��� Genotype 2���� monoclonal gammopa-thy ���!� D�Duvw18���x��\�!"�� de� ���������yz�n��o=p 1� 2��V!{|�bc��}� ��~!�vw27��������� Z���#`�+,��#�u���23� �Y�����B�\�������

� �

�� ��������� CJKFL���U�50��bc��� (�KFL���! Abc��t� �F���F����+,��o?���BA� ���<���6�F�� ��/�����F�! Abc��t�

�� ��������F�� 4� � MonoclonalGammopathy ����bc��� ��������������WX�����t�

� �

1� Cacoub P, Renou C, Rosenthal E, Cohen P,Loury I, Loustaud-Ratti V, Yamamoto AM, et

al. Extrahepatic manifestations associated with

hepatitis C virus infection. A prospective multi-

center study of 321 patients. The GERMIVIC.

Groupe d’Etude et de Recherche en Medecine

Interne et Maladies Infectieuses sur le Virus de

l[Hepatite C. Medicine �Baltimore� 2000; 79:47�56.

2� El-Serag HB, Hampel H, Yeh C, Rabeneck L.Extrahepatic manifestations of hepatitis C

among United States male veterans. Hepatol-

ogy 2002; 36: 1439�1445.3� Pawlotsky JM, Roudot-Thoraval F, Sim-monds P, Mellor J, Ben Yahia MB, Andre C,

Voisin MC, et al. Extrahepatic immunologic

manifestations in chronic hepatitis C and hepa-

titis C virus serotypes. Ann Intern Med 1995;

122: 169�173.4� Cacoub P, Fabiani FL, Musset L, Perrin M,Frangeul L, Leger JM, Huraux JM, et al.

Mixed cryoglobulinemia and hepatitis C virus.

Am J Med 1994; 96: 124�132.5� Cacoub P, Hausfater P, Musset L, Piette JC.Mixed cryoglobulinemia in hepatitis C pa-

tients. GERMIVIC. Ann Med Interne �Paris�2000; 151: 20�29.

6� Liakina V, Speiciene D, Irnius A, Naraskevici-ene J, Barakauskiene A, Semuchiniene T.

Prevalence of cryoglobulinemia in patients

with chronic HCV infection. Med Sci Monit

2002; 8: CR31�36.7� Tanaka K, Aiyama T, Imai J, Morishita Y,Fukatsu T, Kakumu S. Serum cryoglobulin

and chronic hepatitis C virus disease among

Japanese patients. Am J Gastroenterol 1995;

90: 1847�1852.8� Okuse C, Yotsuyanagi H, Okazaki T, YasudaK, Fujioka T, Tomoe M, Hashizume K, et al.

Detection, using a novel method, of a high

prevalence of cryoglobulinemia in persistent

hepatitis C virus infection. Hepatol Res 2003;

27: 18�22.9� Brouet JC, Clauvel JP, Danon F, Klein M,SeligmannM. Biologic and clinical significance

of cryoglobulins. A report of 86 cases. Am J

Med 1974; 57: 775�788.10� Wong VS, Egner W, Elsey T, Brown D, Alex-

ander GJ. Incidence, character and clinical

relevance of mixed cryoglobulinaemia in pa-

tients with chronic hepatitis C virus infection.

Clin Exp Immunol 1996; 104: 25�31.11� Ikeda K, Saitoh S, Kobayashi M, Suzuki Y,

CJKFL���������� ¡M¢£� 457

41

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Tsubota A, Suzuki F, Arase Y, Murashima N,

Chayama K, Kumada H: Distinction between

chronic hepatitis and liver cirrhosis in patients

with hepatitis C virus infection. Practical dis-

criminant function using common laboratory

data. Hepatol Res 18�3�: 252, 200012� Nomura H, Ogo T, Rikimaru N, Ueno S,

Kakuno T, Okamoto O, Shiraishi G, et al.

Hepatitis C virus-related liver damage is related

to cold activation of complement. J Clin Gas-

troenterol 1997; 25: 529�534.13� Wei G, Yano S, Kuroiwa T, Hiromura K,Maezawa A. Hepatitis C virus �HCV�-inducedIgG-IgM rheumatoid factor �RF� complex maybe the main causal factor for cold-dependent

activation of complement in patients with rheu-

matic disease. Clin Exp Immunol 1997; 107:

83�88.14� Nagasaka A, Takahashi T, Sasaki T, Taki-

moto K, Miyashita K, Nakamura M, Waka-

hama O, et al. Cryoglobulinemia in Japanese

patients with chronic hepatitis C virus infec-

tion: host genetic and virological study. J Med

Virol 2001; 65: 52�57.15� Fornasieri A, Bernasconi P, Ribero ML, SinicoRA, Fasola M, Zhou J, Portera G, et al. Hepa-

titis C virus �HCV� in lymphocyte subsets andin B lymphocytes expressing rheumatoid factor

cross-reacting idiotype in type II mixed cryo-

globulinaemia. Clin Exp Immunol 2000; 122:

400�403.16� Mussini C, Ghini M, Mascia MT, Zanni G,Lattuada I, Giovanardi P, Bonacorsi G, et al.

HCV and monoclonal gammopathies. Clin

Exp Rheumatol 1995; 13 Suppl 13: S45�49.17� Mangia A, Clemente R, Musto P, Cascavilla I,La Floresta P, Sanpaolo G, Gentile R, et al.

Hepatitis C virus infection and monoclonal

gammopathies not associated with cryoglobu-

linemia. Leukemia 1996; 10: 1209�1213.18� Andreone P, Zignego AL, Cursaro C, Gra-

menzi A, Gherlinzoni F, Fiorino S, Giannini

C, et al. Prevalence of monoclonal gammo-

pathies in patients with hepatitis C virus infec-

tion. Ann Intern Med 1998; 129: 294�298.19� Perrone A, Deramo MT, Spaccavento F,Santarcangelo P, Favoino B, Antonaci S.

Hepatitis C virus �HCV� genotypes, humanleucocyte antigen expression and monoclonal

gammopathy prevalence during chronic HCV

infection. Cytobios 2001; 106 Suppl 1: 125�134.20� Al-Shemmari SH, Siddique I, Hassan F,

Nkansa-Dwamena D, El-Naga HA, Ameen R.

Monoclonal gammopathy among patients with

chronic hepatitis C infection. Med Princ Pract

2004; 13: 88�90.21� Zignego AL, Giannelli F, Marrocchi ME,Mazzocca A, Ferri C, Giannini C, Monti M, et

al. T �14; 18� translocation in chronic hepatitisC virus infection. Hepatology 2000; 31: 474�479.

22� Zignego AL, Ferri C, Giannelli F, Giannini C,Caini P, Monti M, Marrocchi ME, et al. Preva-

lence of bcl-2 rearrangement in patients with

hepatitis C virus-related mixed cryoglobuline-

mia with or without B-cell lymphomas. Ann

Intern Med 2002; 137: 571�580.23� Kitay-Cohen Y, Amiel A, Hilzenrat N, Buskila

D, Ashur Y, Fejgin M, Gaber E, et al. Bcl-2

rearrangement in patients with chronic hepati-

tis C associated with essential mixed cryoglobu-

linemia type II. Blood 2000; 96: 2910�2912.24� Zuckerman E, Zuckerman T, Sahar D,

Streichman S, Attias D, Sabo E, Yeshurun D,

et al. bcl-2 and immunoglobulin gene rear-

rangement in patients with hepatitis C virus

infection. Br J Haematol 2001; 112: 364�369.25� Sasso EH, Martinez M, Yarfitz SL, Ghillani P,Musset L, Piette JC, Cacoub P. Frequent join-

ing of Bcl-2 to a JH6 gene in hepatitis C virus-

associated t �14; 18�. J Immunol 2004; 173:3549�3556.

26� Bianco E, Marcucci F, Mele A, Musto P, Coti-chini R, Sanpaolo MG, Iannitto E, et al.

Prevalence of hepatitis C virus infection in lym-

phoproliferative diseases other than B-cell non-

Hodgkin’s lymphoma, and in myeloprolifera-

tive diseases: an Italian Multi-Center case-

���� ���� 458

42

Page 7: Cigakukai.marianna-u.ac.jp/idaishi/www/325/06-32-5Orita Mayu.pdf · Gammopathy bc ˘ ˝˛œšˆ WX ž ˘t 1 Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto

control study. Haematologica 2004; 89: 70�76.27� Cicardi M, Cesana B, Del Ninno E, Pappa-lardo E, Silini E, Agostoni A, Colombo M.

Prevalence and risk factors for the presence of

serum cryoglobulins in patients with chronic

hepatitis C. J Viral Hepat 2000; 7: 138�143.28� Dispenzieri A. Symptomatic cryoglobulinemia.Curr Treat Options Oncol 2000; 1: 105�118.

29� Della Rossa A, Tavoni A, Baldini C, Bombar-dieri S. Treatment of chronic hepatitis C infec-

tion with cryoglobulinemia. Curr Opin Rheu-

matol 2002; 14: 231�237.30� Hartmann H, Schott P, Polzien F, Mihm S, UyA, Kaboth U, Pardowitz I, et al. Cryoglobu-

linemia in chronic hepatitis C virus infection:

prevalence, clinical manifestations, response to

interferon treatment and analysis of cryopre-

cipitates. Z Gastroenterol 1995; 33: 643�650.

31� Casaril M, Capra F, Gabrielli GB, Bassi A,Squarzoni S, Dagradi R, De Maria E, et al.

Cryoglobulinemia in hepatitis C virus chronic

active hepatitis: e#ects of interferon-alpha

therapy. J Interferon Cytokine Res 1996; 16:

585�588.32� Zuckerman E, Keren D, Slobodin G, Rosner I,Rozenbaum M, Toubi E, Sabo E, et al. Treat-

ment of refractory, symptomatic, hepatitis C

virus related mixed cryoglobulinemia with ri-

bavirin and interferon-alpha. J Rheumatol

2000; 27: 2172�2178.33� Mazzaro C, Carniello GS, Colle R, Doretto P,Mazzi G, Crovatto M, Santini GF, et al. Inter-

feron therapy in HCV-positive mixed cryo-

globulinaemia: viral and host factors contrib-

uting to e$cacy of the therapy. Ital J Gastroen-

terol Hepatol 1997; 29: 343�350.

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Abstract

A Study of Cryoglobulinemia and Monoclonal Gammopathy Associated

with Chronic Viral Liver Disease C

Mayu Orita, Chiaki Okuse, Hiroshi Yotsuyanagi,

Michihiro Suzuki, and Fumio Itoh

We studied cryoglobulinemia and M-proteinemia associated with chronic liver disease C. Cryoglobulin

was detected in 93 of 186 �50�� patients with chronic liver disease C. The prevalence of cryoglobulinemiawas higher in patients with liver cirrhosis or hepatocellular carcinoma than those with chronic hepatitis.

Cryoglobulin-positive patients had lower levels of serum HCV RNA and complement in addition to higher

levels of serum rheumatoid factor. M-protein was detected in two �4�� of cryoglobulin-positive and one�5�� of cryoglobulin-negative patients. The two cryoglobulin-positive patients had IgM-k-type M-proteinand remarkably-elevated rheumatoid factor. In addition, clinical symptoms associated with cryoglobuline-

mia were found. Our study shows that cryoglobulinemia complicates frequently with chronic liver disease C

and suggests that M-proteinemia is related to excessive production of cryoglobulin.

Department of Internal Medicine, Division of Gastroenterology and Hepatology.

St. Marianna University School of Medicine.

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