Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin’s lymphoma, and cancer

Table 1 Hepatitis C virus syndrome: strength of association between hepatitis C virus infection and different diseases

Strong association1	Significant association2	Possible association3	Anecdotal association4
Chonic hepatitis	B-cell NHL	Sicca syndrome/SS	PM/DM
Cirrhosis	Monoclonal gammopthies	Polyarthritis	PAN
HCC	Porphyria cutanea tarda	Pruritus	Behçet’s syndrome
Mixed cryoglobulinemia s./	Glomerulonephritis	Osteosclerosis	Chronic urticaria
Cryoglobulinemic vasculitis	Autoimmune thyroiditis Papillary thyroid cancer Diabetes m. type 2	Fibromyalgia Peripheral neuropathy Lung alveolitis Autoimmune hepatitis Cardiovascular inv. Lichen planus	Psorias Mooren corneal ulcer

¹The HCV is the etiological agent or it is detectable in the majority of patients;

²HCV is detectable in a significant proportion of pts compared to general population, with heterogeneous geographical distribution, its potential role is supported by pathogenetic studies;

³A role of HCV infection has been suggested by cohort studies or

⁴by some anecdotal observations. HCC: Hepatocellular carcinoma; SS: Sjögren’s syndrome; PM/DM: Polymyositis/dermatomyositis; PAN: Panarteritis nodosa; HCV: Hepatitis C virus.

Table 2 Clinico-epidemiological and laboratory features of mixed cryoglobulinemia¹

Epidemiological features
Mean age at disease onset ± SD, yr (range)	55 ± 12 (29-72)
Mean disease duration ± SD, yr (range)	12 ± 10 (1-40)
Female/male ratio	3
Clinical features
Purpura	98
Weakness	98
Arthralgias	91
Arthritis (non-erosive)	8
Raynaud’s phenomenon	32
Sicca syndrome	51
Peripheral neuropathy	81
Renal involvement2	31
Liver involvement	73
B cell non-Hodgkin’s lymphoma	11
Hepatocellular carcinoma	3
Serological and virological features
Mean cryocrit (SD)	4.4% (12)
Type II/type III mixed cryoglobulins	2/1
Mean C3 (SD) (nv 60-130 mg/dL)	93 (30)
Mean C4 (SD) (nv 20-55 mg/dL)	10 (12)
Anti-nuclear antibodies	30
Anti-mitochondrial antibodies	9
Anti-smooth muscle antibodies	18
Anti-extractable nuclear antigen antibodies	8
Anti-HCV antibodies ± HCV RNA	92
Anti-HBV antibodies	32
HBsAg	1

¹Data are referred to 100 consecutive, unselected Italian patients with mixed cryoglobulinemia syndrome (MCs) evaluated at the end of follow-up;

²Membranoproliferative glomerulonephritis type I. HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.

Table 3 Association between hepatitis C virus infection and B-cell non-Hodgkin’s lymphoma: Epidemiological studies

Significant association1			No association1
Ref.	Country	Prevalence2	Ref.	Country	Prevalence2
Ferri et al[69]	Italy	34% (17/50)	Brind et al[104]	United Kingdom	0% (0/63)
Luppi et al[70]	Italy	42% (29/69)	Hanley et al[105]	United Kingdom	0% (0/72)
Mazzaro et al[71]	Italy	28% (56/199)	McColl et al[106]	Scotland	0% (0/110)
Musolino et al[72]	Italy	20.8% (5/24)	Thalen et al[107]	The Netherlands	0% (0/115)
Silvestri et al[73]	Italy	8.9% (42/470)	Ellenrieder et al[108]	Germany	4.3% (3/69)
De Rosa et al[74]	Italy	22.4 (59/263)	Timoraglu et al[109]	Turkey	0% (0/48)
Zuckerman et al[75]	Mexico and United States	22% (26/120)	Collier et al[110]	Canada	0% (0/101)
Catassi et al[76]	Italy	11.2% (16/143)	Shariff et al[111]	Canada	2.3% (2/88)
Kashyap et al[77]	United States	11.5% (36/312)	Udomsakdi-Auewarakul et al[112]	Thailand	2.3% (3/130)
Luppi et al[78]	Italy	22.3% (35/157)	Hausfater et al[113]	France	1.83% (3/164)
Cucuianu et al[79]	Romania	29.5% (20/68)	Isikdogan et al[114]	Turkey	0% (0/119)
Vallisa et al[80]	Italy	37.1% (65/175)	Giannoulis et al[115]	Greece	1.9% (2/108)
Paydas et al[81]	Turkey	11.4% (26/228)	Sonmez et al[116]	Turkey	2.8% (3/109)
Harakati et al[82]	Saudi Arabia	21.4% (12/56)	Okan et al[117]	Turkey	3.1% (8/258)
Mizorogi et al[83]	Japan	17% (17/100)	Park et al[118]	South Korea	2.1% (5/235)
Zucca et al[84]	Switzerland	9.4% (17/180)	Varma et al[119]	India	1.75% (1/57)
3Pioltelli et al[85]	Italy	16% (48/300)
Sanchez Ruiz et al[86]	Spain	11.7% (9/77)
Chindamo et al[87]	Brazil	8.2% (9/109)
De Renzo et al[88]	Italy	17.3% (39/227)
Imai et al[89]	Japan	13.4% (21/156)
Gisbert et al[90]	Spain	7% (7/99)
Mele et al[91]	Italy	17.5% (70/400)
Yenice et al[92]	Turkey	7.1% (6/84)
Iwata et al[93]	Japan	11% (16/145)
Gisbert et al[94]	Spain	5.8% (5/86)
Talamini et al[95]	Italy	19.6% (44/225)
Cowgill et al[96]	Egypt	42% (95/227)
Engels et al[97]	United States	3.9% (32/813)
de Sanjose et al[98]	Spain	3.9% (172/4784)
Spinelli et al[99]	Canada	2.4% (19/795)
Chuang et al[100]	Taiwan	11% (31/346)
Libra et al[101]	Italy	19.7% (539/2736)
Kang et al[102]	South Korea	2.8% (76/3932)
Nosotti et al[103]	Italy	9.2% (19/207)
Range		2.4%-42%			0%-4.3%

¹Compared to controls;

²HCV-RNA and/or anti-HCV;

³The prevalence of HCV infection in B-NHL was statistically significant compared to controls, but not confirmed by odds ratio method to estimate the relative risk. HCV: Hepatitis C virus.