Oral manifestations of hepatitis C virus infection

Table 1 Main summary of the recent 3 meta-analyses on lichen planus and hepatitis C virus

Ref.	Country	Period covered by search	Type of studies included	Studies included in the meta-analysis	Cases/controls	Main results	Quality assessment of the included studies		1Quality assessment of the systematic review process
								Tool used
Shengyuan et al[15]	China	NA	Case control or control-existing studies	70	24987/65022	The prevalence of HCV exposure among patients with LP was higher than in control participants (OR = 5.4; 95%CI: 3.5-8.3)	Yes	According to Robinson et al[17]	High
			Clinical or histological LP diagnosis	58 on HCV prevalence in LP	35570/139120	The risk of LP among patients with HCV was higher than compared controls (OR = 2.5; 95%CI: 2.0-3.1)
			HCV status diagnosed by serology or PCR	12 on LP prevalence in HCV+
Lodi et al[13]	Italy	Jan 1966-Nov 2007	Controlled studies	39	22544/2860	LP patients have significantly higher risk than controls of being HCV seropositive (OR = 4.85; 95%CI: 3.58-6.56)	Yes	Characteristics of the study group, appropriateness of the control group, prospective design	High
			Clinical and histological LP diagnosis	33 on HCV prevalence in LP; 6 on LP prevalence in HCV+	3955/1242	HCV patients have an increased risk of having LP (OR = 4.47; 95%CI: 1.84-10.86)
			HCV status diagnosed by serology
Petti et al[14]	Italy	NA	Cross-sectional or case- control studies	44	NA	The overall risk for OLP among anti-HCV positive subjects was significantly higher than controls (OR = 2.8; 95%CI: 2.4-3.2)	No	NA	Uncertain
			Clinical or histological LP diagnosis. Any HCV testing			The fraction of global OLP cases associated with HCV (population attributable fraction) was 2.1% (95%CI: 1.9%-2.2%)

Modified from Baccaglini et al[16]. ¹According to PRISMA (Moher et al[18]);

²LP vs controls;

³HCV+ vs HCV-; NA: Not available; LP: Lichen planus; HCV: Hepatitis C virus.

Table 2 Hepatitis C virus detection in lichen planus lesional tissue n (%)

Country	Ref.	n	Patients HCV positive	Patients with oral lesions	Detection of HCV in specimens of lichen planus	Tissue sample	Technique	Ratio of +/- strands	Oral mucosa/skin HCV RNA
									Genomic strand	Negative strand
Italy	Sansonno et al[22]	7	0	NA	0 (0)	Fresh	IHC	-	-	-
	Mangia et al[23]	19	19	0	0 (0)	Fresh	rTth RT-PCR	-	-	-
	Carrozzo et al[24]	12	12	12	10 (83)	Fresh	rTth RT-PCR, SA, PhA	1-64 Various	10 (83)	4 (33)
	Pilli et al[25]	4	4	4	3 (75)	Fresh	rTth RT-PCR	-	3 (75)	0 (0)
	Femiano et al[26]	25	25	25	0 (0)	Unclear	RT-PCR	-	0 (0)	NA
Japan	Nagao et al[27]	14	14	14	13 (93)	Fresh	PCR, SA	-	13 (93)	3 (21)
	Kurokawa et al[28]	3	3	2	3 (100)	Fresh	rTth RT-PCR	-	3 (100)	3 (100)
Spain	Arrietaet al[29]	23	23	23	23 (100)	paraffin-embedded	ISH	-	23 (100)	23 (100)
	Lazaro et al[30]	5	5	0	5 (100)	paraffin-embedded	ISH, IHC	-	5 (100)	5 (100)
Turkey	Erkek et al[31]	5	5	4	5 (100)	paraffin-embedded	RT-PCR	-	5 (100)	NA
United Kingdom	Roy et al[32]	27	0	27	0 (0)	NA	RT-PCR	-	0 (0)	NA
	Boyd et al[33]	27	2	NA	0 (0)	paraffin-embedded	IHC	-	-	-
United States	Harden et al[34]	4	4	1	0/0	paraffin-embedded	RT-PCR	-	0 (0)	NA
Total	OLP (%)		85		56 (66)				56	32 (58)
	LP (%)		21		7 (33)				7	6 (85)

Modified from Baccaglini et al[16]. NA: Not available; IHC: Immunohistochemistry; ISH: In situ hybridization; PCR: Polymerase chain reactions; rTth: Recombinant Thermus thermophilus; SA: Sequence analysis; PhA: Phylogenetic analysis; LP: Lichen planus; HCV: Hepatitis C virus; RT-PCR: Real-time reverse transcription-polymerase chain reaction.

Table 3 Main clinical, serological, histological, genetic differences between sialadenitis in Sjogren’s syndrome and hepatitis C virus +ve patients

Variable	Sjögren's syndrome	Hepatitis C virus
Sicca symptoms	Commonly present	Usually absent or modest
Parotid swelling	Moderate to severe	Mild to moderate
Extra-glandular manifestations	Mainly pulmonary, gastrointestinal, renal, and neurologic involvement	Mainly gastrointestinal and musculo-skeletal involvement
Histology	Periductal lymphocytic infiltration	Pericapillary lymphocytic infiltration
Infiltrating lymphocytic phenotype	Predominantly CD4+ T cells	Mixed CD4+/CD8+ T cells
Autoantibodies	High-frequency RF, ANA, anti-Ro/SSA and anti-La/SSB, alpha-fodrin antibodies	High frequency of RF, ANA, alpha-fodrin, low prevalence of anti-Ro/SSA and anti-La/SSB antibodies, high frequency of cryoglobulins
HLA association	B8, DR2 and DR3	DQB1*02
Lymphomagenesis	Preferentially affecting salivary glands	Affecting both liver and salivary glands

Modified from Vitali[60]. Sicca symptoms: Dry eyes/dry mouth. ANA: Antinuclear antibodies; RF: Rheumatoid factor; HLA: Human leukocyte antigen.

Table 4 Prevalence of hepatitis C virus infection in patients with Sjögren’s syndrome

Country	Ref.	n	SjS Diagnostic Criteria	HCVve+ (%)
France	de Bandt[61]	20	NA	10
	Loustaud-Ratti et al[56]	26	NA	8
	Mariette et al[62]	20	1Fox I	10
	Barrier et al[63]	22	NA	9
	Vidal et al[64]	28	1Fox I	14
	Wattiaux et al[65]	109	European	3
	Boscagli et al[50]	23	NA	5
	Jorgensen et al[66]	62	European	19
Germany	Potthoff et al[67]	73	2AECG	18
Greece	Vitali et al[68]	22	Vitali	5
Hungary	Szodoray et al[69]	213	European	6
India	Wanchu et al[70]	23	European	4.4
Italy	Aceti et al[71]	26	1Fox I	0
	Vitali et al[68]	44	Vitali	5
	Frisoni et al[72]	26	NA	4
	Ceribelli et al[73]	305	2AECG	3
Japan	Masaki et al[74]	98	NA	11
Spain	García-Carrasco et al[75]	90	European	14
	Coll et al[76]	31	European	10
	Fernandez-Campillo et al[77]	26	European	19
	Selva-O’Callaghan et al[78]	98	European	7
Sweden	Verbaan et al[52]	53	Copenhagen	2
United Kingdom	Porter et al[79]	18	European	0
United States	King et al[80]	44	NA	0
United States	Marrone et al[81]	100	3Fox II	1

Modified from Carrozzo[6].

¹Fox et al[82]. In contrast to the Fox (San Diego) classification system, the European-proposed (including Vitali and Copenhagen) criteria can be fulfilled without a requirement for histologic or serologic abnormality;

²American-European Consensus Guidelines (AECG) (Vitali et al[83]): in this classification the presence of HCV is considered an exclusion criterion for SjS;

³Fox and Saito[84]: The last Fox classification excludes patients with a history of pre-existing diseases such as hepatitis C, lymphoma, sarcoidosis, or other causes of lymphocytic infiltrative disease. SjS: Sjögren’s syndrome; HCV: Hepatitis C virus; NA: Not available.