In this study, we demonstrated that HCV infection is significantly associated with the development of lichen planus. The odds ratio was 6.58 (95% confidence interval 2.89-15.69). This odds ratio was higher than that of a meta-analysis published recently (odds ratio 2.8) [32
]. Hypoalbuminemia and smoking also increased the risk of lichen planus. However, substitutions of aa 70 and/or 91 and ISDR regions had no impact on the development of lichen planus.
HCC is one of the most common malignancies, especially in Japan. The most important risk factors of HCC are chronic hepatitis C, B and cirrhosis. The effect of Peg-IFN and ribavirin (RBV) treatment on chronic HCV infection has been established in several controlled clinical studies [33
]. The effects of IFN are summarized as follows: elimination of HCV, reduction of hepatic inflammation, improvement in liver fibrosis, and reduction in hepatocarcinogenesis [34
]. In Japan, 70% of refractory cases are infected with genotype 1b with a high HCV RNA load. Japanese patients with chronic HCV infection are getting older. Viral mutations leading to aa substitutions in the HCV core region (70 and/or 91) and ISDR of NS5A have been shown to be valuable as predictors of virological response to combination therapy with Peg-IFN and RBV [2
]. In addition, single nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene locus have been reported to affect the efficacy of Peg-IFN and RBV therapy in chronic hepatitis with HCV genotype 1b infection [35
]. In Japan, there is an established standard therapy for chronic hepatitis C based on guidelines including viral factors such as genotype and levels of HCV RNA. More recently, the effects of variation of IL28B and aa substitutions in the HCV core region and ISDR of NS5A have been established.
The association between lichen planus and HCV infection seems to be more common in individuals living in areas of Japan and Italy [11
]. The difference in the prevalence HCV-infection in patients with lichen planus seems to be due to geographic differences in HCV infection, selection of study subjects such as sex, average age, and diagnosis in the respective countries, and some genetic predisposition such as the HLA-DR6 allele. The HLA-DR6 allele is reported to be significantly more common in Italian patients with lichen planus and HCV [37
]. Moreover, not all reported studies included screening of hepatic damage and measurement of serum HCV RNA to determine the presence or absence of hepatic diseases. The areas of our study are in the northern Kyushu region, where the HCV infection rate and the mortality rate from HCC are the highest in Japan. Previous reports indicated that there are no differences in the viral factors such as viral load and genotype between HCV-infected patients with lichen planus and those without [17
]. This study ruled out a direct association of viral factors, such as substitutions of aa 70 and/or 91 and in the ISDR region, with the development of HCV-related lichen planus.
We reported that the prevalence of HCV-related lichen planus increased as the subjects grew older in Japan [38
]. We also reported previously the prevalence of HCV infection among lichen planus among 45 patients who visited the Department of Oral Surgery at our hospital from November 1993 to April 1994 [12
]. The mean age (68.1 years) of the 59 patients (group 1-A) in the present study was higher than that (61.1 years) of the previous 45 patients.
We demonstrated a strong association between hypoalbuminemia and mortality in a hyperendemic area (X town) of HCV infection in Japan [39
]. Residents with hypoalbuminemia had a mortality of 68.0%; dramatically higher than the rate of 12.1% among residents who had normal albumin levels. Hypoalbuminemia was an independent risk factor for the development of lichen planus. Recent studies have demonstrated the efficacy of branched-chain amino acid (BCAA) supplementation in improving hypoalbuminemia in cirrhotic patients [40
]. The effects of BCAA intake have been investigated in a number of disease models, including obesity and metabolic disorders, liver disease, impaired immunity, muscle atrophy, cancer, and a variety of injury (postoperative, trauma, burn, and sepsis) [41
]. Among Japan's aging population, BCAA intake seems to be useful for HCV-infected patients with lichen planus.