by studies in experimental animals in which neutrophil C-X-C chemokines are potent chemoattractants that depletion before a hepatic insult can limit tissue injury. 1,6,7 are believed to mediate neutrophilic inflammation in For neutrophils to emigrate from the circulation to the heseveral organs. Recent studies suggest a role for C-X-C patic parenchyma, they must respond to a specific chemotacchemokines in the pathogenesis of neutrophilic hepatitic signal. We and others have shown that liver cells are tis but do not prove causation. We investigated the biocapable of producing neutrophil chemoattractants belonging logical consequences of hepatic chemokine production to the C-X-C family of chemokines. [8][9][10][11][12] Among the C-X-C in vivo by transiently overexpressing cytokine-induced chemokines produced by liver cells are interleukin (IL)-8 and neutrophil chemoattractant (CINC), a member of the Ca related compound in the rat called cytokine-induced neutro-X-C chemokine family, in intact rats. Rats were injected phil chemoattractant (CINC). IL-8 and CINC are 47% homolintraportally with a replication-defective recombinant ogous in nucleotide sequence; from a functional point of view, adenovirus containing the CINC complementary DNA the two are almost identical. Each compound has the ability (cDNA). Within 4 days, treated animals had high levels to attract neutrophils from humans and rats, respectively, in of CINC in both liver tissue and plasma. Rats overexnanomolar concentrations in vitro. 13pressing CINC exhibited an eightfold increase in circuHigh levels of IL-8 or CINC have been reported in humans lating neutrophils; they also developed severe hepatic and rats with neutrophilic hepatitis, 4,5 which documents an injury, characterized by a 6-to 25-fold increase in plasma association between hepatic chemokine production and neutransaminases and marked hepatic inflammation on bitrophilic liver injury in vivo. However, the precise role of opsy. Liver disease in CINC-producing rats correlated chemokines in the pathogenesis of neutrophilic hepatitis repositively with the number of neutrophils sequestered mains unresolved, because these compounds represent but in the hepatic parenchyma. Tissue injury was attributed one of many inflammatory mediators produced locally in liver directly to chemokine overproduction, because control injury. Indeed, neutrophilic hepatitis is accompanied not only rats infected with adenoviruses lacking the CINC cDNA by hepatic chemokine induction but also by local upregulation did not produce CINC and developed only minor hepatic of IL-1, IL-6, tumor necrosis factor, and platelet-activating abnormalities. These experiments provide direct evifactor. 11,15,16 Oxyradicals and arachidonic acid metabolites dence that C-X-C chemokines, when expressed in suffialso accumulate in acute inflammatory liver disease. 17,18cient quantity in the liver in vivo, induce neutrophil reThese too may enhance neutrophil recruitment and liver cruitment and tissue invasion and provoke severe liver damage. In such...

Epidemiologic links between chronic hepatitis C and herpes simplex type-2 infection have been suggested; however, type-specific tests for HSV-2 infection have not been validated in patients with chronic hepatitis C infection. The Focus HerpeSelect(®) HSV-2 IgG (Cypress, California) assay and the Biokit HSV-2 rapid assay (Biokit USA, Lexington, MA) were performed on serum samples obtained from 84 veterans with chronic hepatitis C who demonstrated a previously positive HSV-2 serologic test in their medical records. Using the Biokit HSV-2 as the comparator assay, the positive predictive value, and specificity for the HerpeSelect(®) HSV-2 assay were 62.1% (95%CI: 49.3-73.8) and 41.9% (95%CI: 27.0-57.9), respectively. Increasing the HerpeSelect(®) HSV-2 index value defining a positive test result from >1.1 to ≥2.89 increased the assay's specificity to 97.7% (95%CI: 87.7-99.6) and the positive predictive value to 94.1%(95%CI: 71.2-99.0). J. Med. Virol. 9999: 1-5, 2015. © 2015 Wiley Periodicals, Inc. In veterans with chronic hepatitis C infection, HerpeSelect(®) HSV-2 index values between 1.1 and 2.89 should be confirmed with an alternate test for HSV-2 infection.