Association of Helicobacter species with hepatitis C cirrhosis with or without hepatocellular carcinoma

Abstract

Background and aims: Recent studies have suggested that bacterial coinfection with Helicobacter species in patients already infected with hepatitis C virus (HCV) could be involved in the development of cirrhosis and hepatocellular carcinoma (HCC). A retrospective cross sectional study was performed in order to explore the association between Helicobacter species and HCV associated liver diseases. Methods: The presence of Helicobacter species was tested by polymerase chain reaction on liver samples from four groups of patients. Results: Helicobacter 16S rDNA was found in only 4.2% of liver samples from control patients (n = 24) and in 3.5% of liver samples from patients with non-cirrhotic chronic hepatitis C (n = 29) while it was found in 68.0% of liver samples from patients with HCV positive cirrhosis without HCC (n = 25) as well as in 61.3% of cirrhotic liver samples from patients with HCV positive cirrhosis and HCC (n = 31). In addition, when the HCC tumour tissue was tested (n = 21), 90.5% of samples were positive. DNA from Helicobacter pyloriand Helicobacter pullorum-like organisms was found. Conclusions: There is an association between the presence of Helicobacter species DNA in the liver and hepatitis C cirrhosis, with or without HCC. Indeed, the presence of these bacteria could be the result of structural changes in the liver. Alternatively, Helicobacter species could be a co-risk factor in HCV chronic liver diseases. This result warrants prospective studies to determine the possible causal role of these bacteria in the progression of chronic hepatitis C.

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.…”

“…13 Reportedly, H. pylori infection occurs with a high frequency in patients with cirrhosis and hepatocellular carcinoma (HCC), which may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients. [14][15][16][17] Several studies have shown that H. pylori genomic sequences could be detected in the liver of patients with HCC. 18,19 H. hepaticus, a newly recognized Helicobacter sp., was experimentally proven to cause chronic hepatitis and HCC in mice.…”

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

“…106(6): 748-754, September 2011 The hypothesis that Helicobacter spp might be a risk factor for human liver diseases has arisen after the discovery of Helicobacter hepaticus and its association with murine hepatitis and hepatocellular carcinoma (HCC). Subsequent studies in humans have shown the presence of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases, mainly cirrhosis and/ or HCC secondary to hepatitis B virus (HBV) and hepatitis C virus (HCV) (Avenaud et al 2000, Dore et al 2002, Fan et al 2002, Verhoef et al 2003, Rocha et al 2005, Pellicano et al 2008. Although these studies have contributed to the debate on the participation of Helicobacter species in the severe human liver disease outcomes, no explanation that justifies the presence of the bacterium in the human liver has yet been proposed.…”

Natural and experimental Helicobacter pullorum infection in Brown Norway rats

“…Faecal DNA samples from 20 BN rats were shipped to our laboratory from Taconic Farms after routine testing discovered Helicobacter in mice where the BN rats were co-housed in the same barrier. Samples were screened for Helicobacter species by PCR using 16S rRNA gene genus-specific primers and H. pullorum cytolethal distending toxin B (cdtB) gene speciesspecific primers (Boutin et al, 2010;Fox et al, 1998;Rocha et al, 2005). Samples confirmed as H. pullorum were subjected to restriction fragment length polymorphism (RFLP) analysis following amplification using Helicobacter genus-specific primers.…”

“…In another case, H. pullorum was isolated from the faeces of a male with diarrhoea and elevated liver enzymes (Burnens et al, 1994). H. pullorum has also been identified by PCR in humans with inflammatory bowel disease, hepatitis, cholecystitis and hepatocelluar carcinoma (Castéra et al, 2006;Fox et al, 1998;Rocha et al, 2005;Veijola et al, 2007). A recent report identified an association between EHS and Crohn's disease, with H. pullorum being one of the most prevalent EHS identified (Laharie et al, 2009).…”