Hepatitis C virus-related lymphoproliferative disorders: An overview

Table 1 Classification of extrahepatic manifestations of HCV infection

A: Association defined on the basis of high prevalence and pathogenesis
Mixed cryoglobulinemia (complete or incomplete clinical syndrome)
B: Association defined on the basis of higher prevalences than in controls
B-cell non-Hodgkin’s lymphoma
Monoclonal gammopathies
Porphyria cutanea tarda
Lichen planus
C: Associations to be confirmed/characterized
Autoimmune thyroiditis
Thyroid cancer
Sicca syndrome
Alveolitis-Lung fibrosis
Diabetes mellitus
Non-cryoglobulinemic nephropathies
Aortic atherosclerosis
D: Anecdotal observations
Psoriasis
Peripheral/central neuropathies
Chronic polyarthritis
Rheumatoid arthritis
Polyartheritis nodosa
Bechet’s syndrome
Poly/dermatomyositis
Fibromyalgia
Chronic urticaria
Chronic pruritus
Kaposi’s pseudo-sarcoma
Vitiligo
Cardiomyopathies
Mooren corneal ulcer
Erectile dysfunctions
Necrolytic acral erythema

Table 2 IFN monotherapy in HCV-related mixed cryoglobulinemia

Author	Year	No. patients	Treatment	CS	Treatment duration (months)	EOT response	Sustained response
Ferri	1993	15	2 MIU IFN/d (1 m) – 2 MIU IFN × 3/w (5 m)	Yes	6	80%
Ferri	1993	26	2 MIU IFN/d (1 m) – 2 MIU IFN × 3/w (5 m)	Yes	6	100%	0
Marcellin	1993	2	3 MIU IFN × 3/w		6	50%
Johnson	1993	4	1-10 MIU IFN	No	2-12	75%1
Misiani	1994	27	1.5 MIU IFN × 3/w (1 w) – 3 MIU IFN × 3/w (23 w)	No	6	60%	0
Dammacco	1994	15	3 MIU IFN × 3/w	No	12	53.30%	25%
		16	3 MIU IFN × 3/w	Yes	12	52.90%	33.30%
Johnson	1994	14	Variable IFN	No		01
Mazzaro	1994	18	3 MIU IFN × 3/w	No		28%
Mazzaro	1995	18	3 MIU IFN × 3/w	No	6	28%	11%
		18	3 MIU IFN × 3/w	No	12	39%	22%
Casaril	1996	25	6 MIU IFN × 3/w	No	6	52%2
Cohen	1996	20	3 MIU IFN × 3/w			60%3	9%3
Akriviadis	1997	20	3-5 MIU IFN × 3/w	No	6-12	65%2	33%2
Casato	1997	31	3 MIU IFN/d (3 m) – 3 MIU IFN × 3/w (≥ 9 m)	No	≥ 12	62%

CS: corticosteroids; MIU: millions of international units; d: daily; m: months; w: week; EOT: end of treatment; ^s: Kidney function improvement;

²: Cryoglobulins disappearance,

³: both complete and partial MC syndrome response. From: Zignego A.L. Postgraduate Course of the 41st Annual Meeting of the EASL, 2006, modified.

Table 3 Combined IFN (recombinant or pegylated) + ribavirin therapy in HCV-related mixed cryoglobulinemia

Author	Year	No. patients	Treatment	CS	Treatment duration (months)	EOT response	Sustained response
Durand	1998	5 NR	RBV	No	10-36	100%	0%
Calleja	1999	18	3 MIU IFN × 3/w	No	12	55%	28%
		8 NR	3 MIU IFN × 3/w + RBV	No	12	63%	38%
Zuckerman	2000	9 NR	3 MIU IFN × 3/w + RBV	No	6	78%
Cacoub	2002	14	Variable IFN + RBV	variable	6-56		71%
Mazzaro	2003	27 NR or Rel	3 MIU × 3/w + RBV	No	12	85%
Alric	2004	18	3 MIU × 3/w or Peg-IFN + RBV	No	≥ 18		70%
Cacoub	2005	9	Peg-IFN 1.5 μg Kg-1 w-1 + RBV		≥ 10		88%
Mazzaro	2005	18	Peg-IFN 1 μg Kg-1 w-1 + RBV	No	12	89%	44%

CS: corticosteroids; MIU: millions of international units; d: day; m: months; w: week; EOT: end of treatment; NR: non responders; Rel: relapser; RBV: ribavirin. From: Zignego A.L. Postgraduate Course of the 41st Annual Meeting of the EASL, 2006.