Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.
To assess the aetiology of liver disease associated with lichen planus, we prospectively studied 70 consecutive newly diagnosed patients with oral lichen planus (OLP) living in northwest Italy (Piemonte) and 70 controls matched for age and sex with other oral keratoses coming from the same district. Twenty-two patients with OLP (31.4%) and 9 controls (12.9%) were found to be affected by chronic liver disease (CLD) (P = 0.014). In sixteen of the 22 OLP patients with CLD the liver disease was hepatitis C virus (HCV)-related, whereas 2 of the 9 controls had a HCV-related CLD (P = 0.016). In another OLP case, liver damage was related to a combination of HCV and alcohol abuse. The prevalence of HCV antibodies in the whole OLP group (27.1%) was significantly higher than in controls (4.3%) (P = 0.014), whereas no difference was found between the OLP and control groups regarding hepatitis B virus markers and other common causes of CLD. HCV infection was more frequently found in patients with erosive OLP (58.8%) than in patients with non-erosive OLP (13.2%) (P = 0.004). Serum HCV-RNA was detected by polymerase chain reaction (RT-PCR) in the majority (93.7%) of OLP patients who had HCV antibodies. Excluding OLP and control patients with HCV markers, there was no difference between the two groups regarding frequency of CLD. Our data show that HCV is probably the main pathogenic factor in liver disease of Italian patients with OLP, and suggests that HCV could be involved in the pathogenesis of OLP.
As the human tetraspanin CD81 binds hepatitis C virus (HCV) envelope glycoprotein E2, we addressed the role CD81 may play in cellular trafficking of HCV envelope proteins. Studies on HCV life cycle are complicated by the lack of a robust cell culture system; we therefore transfected mammalian cells with HCV E1-E2 cDNA, with or without human CD81 (huCD81) cDNA. In the absence of huCD81, HCV envelope proteins are almost completely retained in the endoplasmic reticulum. Instead, when huCD81 is present, a fraction of HCV envelope proteins passes through the Golgi apparatus, matures acquiring complex sugars and is found extracellularly associated with exosomes. These are 60-100-nm membrane vesicles enriched in tetraspanins, released into the extracellular milieu by many cell types and having fusogenic activity. We also report that human plasma contains exosomes and that in HCV patients, viral RNA is associated with these circulating vesicles. We propose that the HCV-CD81 complex leaves cells in the form of exosomes, circulates in this form and exploits the fusogenic capabilities of these vesicles to infect cells even in the presence of neutralizing antibodies.
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