Helicobacter pylori promotes hepatic fibrosis in the animal model

Abstract

Helicobacter pylori infection has been reported to be very common in patients with chronic liver diseases, including cirrhosis. To elucidate the pathological effect of H. pylori infection on the progression of hepatic fibrosis, C57BL/6 mice and Sprague-Dawley rats were orally inoculated with H. pylori, and hepatic fibrosis was induced with carbon tetrachloride (CCl 4 ) administration. We observed the histopathological changes and the presence of H. pylori genes by PCR in the liver. Significant increase in the fibrotic score as well as in serum alanine aminotransferase and aspartate aminotransferase levels was shown in the CCl 4 þ H. pylori group compared with that in the CCl 4 -treated group. Compared with the CCl 4 -treated group, a-smooth muscle actin and transforming growth factor-b1 were enhanced; however, senescence marker protein-30, a multifunctional protein protecting hepatocytes against oxidative stress and apoptosis, was suppressed in the CCl 4 þ H. pylori group. The 16S rRNA (400 bp) was demonstrated by PCR for H. pylori genes from genomic DNA extracted from the liver, and H. pylori-infected mice showed 93.8% (15 of 16) seropositivity by contrast with seronegativity in all H. pylori-noninfected mice. In addition, immunohistochemical study against H. pylori showed positive antigen fragments in the liver of the infected groups. Consequently, our data suggest that H. pylori infection could be an important contributing infectious factor to the development of liver cirrhosis.

Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-β1-induced inflammatory signaling

“…[14][15][16] However, the pathological role of chronic H. pylori infection in liver diseases remains controversial. Our earlier report showed that H. pylori promotes hepatic fibrosis in rat and mouse models, in which Goo et al 22 showed that H. pylori infection for 4-months duration caused functional and morphological degenerative changes in hepatocytes with slight focal necrotic and inflammatory changes, in spite of there being no severe hepatitis present. These changes in H. pylori-infected livers could provide a synergistic combination of liver damage when exposed to additional harmful stimuli.…”

“…To elucidate the mechanism by which H. pylori accelerate hepatic fibrosis, the same liver samples that were described in an earlier paper 22 were used in this study. Animal procedures were conducted in accordance with the NIH guidelines.…”

“…According to the earlier study, 22 obvious signs of hepatic fibrosis in H. pylori plus CCl 4 treatment group were observed compared with that in CCl 4 treatment alone, whereas H. pylori treatment alone did not induce hepatic fibrosis; the grade of fibrosis seen in H. pylori plus CCl 4 -treated mice increased by about 60% (Po0.01) as compared with that of CCl 4 -alone-treated mice and liver necrosis was augmented by twofold increases, based on serum AST/ALT levels (Po0.05). In the study, another serum biochemical analysis was presented.…”

“…Meanwhile, our recent study supports a possible implication of H. pylori in the pathogenesis of hepatic fibrosis and cirrhosis by showing that H. pylori significantly accelerated the CCl 4 -induced hepatic fibrosis in both rats and mice models. 22 The recognition of H. pylori as a possible risk factor for fastidious liver diseases such as cirrhosis and HCC might have a practical impact on the therapy for them, by treatment of the infection and not liver transplantation or any longterm management. A recent outstanding study showed that bacterial lipopolysaccharide (LPS) intoxication promoted hepatic fibrosis by enhancing the transforming growth factorbeta1 (TGF-b1) signaling through a toll-like receptor 4 (TLR4)-myeloid differentiation primary response gene 88 (MyD88)-nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) axis in HSCs, which provides a novel link between pro-inflammatory and pro-fibrogenic signals.…”

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

“…Finally, the excessive accumulation of ECM components promotes the formation of the most prominent periductal fibrosis during O. viverrini and H. pylori coinfection. Relevantly, a combination of H. pylori and carbon tetrachloride treatment can enhance the severity of hepatic fibrosis in animals (19). Also, in chronic hepatitis C patients, coinfection with H. pylori can enhance liver fibrosis and cirrhosis (20).…”