Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma (original) (raw)
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Helicobacter species sequences in liver samples from patients with hepatocellular carcinoma
Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer. METHODS: Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cag A gene analysis were also performed. RESULTS: Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis. In three samples of the first group the result was uncertain. H pylori was revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other. CONCLUSION: Helicobacter spp., carcinogenic in mice, were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease.
Digestive diseases and sciences, 2002
Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). HCC represents one of the most common human cancers. Incidence rates for this tumor vary widely on a worldwide, suggesting that environmental factors such as infectious microorganisms, carcinogens, or nutrition play a role in its pathogenesis. Several Helicobacter spp. colonize the liver of animals and induce hepatitis. The aim of this study was to determine whether Helicobacter infection was associated with HCV-related liver diseases in humans. Liver tissue samples, including biopsy and surgically excised tissues, were collected from patients positive for hepatitis C viruses (HCV) RNA in the serum. Genomic DNA was extracted from sections of formalin-fixed paraffin-embedded tissues by using the QIAamp Tissue Kit and subjected to polymerase chain reaction (PCR) analysis using two sets of Helicobacter-specific 16S ribosomal RNA primers. To identify positive samples for H. pylori, a set of primers specific ...
Gut, 2005
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 species and liver diseases: association or causation?
The Lancet Infectious Diseases, 2008
The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocarcinoma in mice has stimulated interest in looking for Helicobacter spp in human liver samples. These bacteria could be a risk factor for the progression of liver disease to cirrhosis and hepatocellular carcinoma, especially among patients chronically infected with hepatitis C virus. We reviewed the studies done on this topic, and, with the exception of one, all studies reported an association between the presence of Helicobacter spp and liver disease. However, these data are weakened by the fact that Helicobacter spp DNA was detected but no bacteria could be grown, and by the diffi culties in identifying the Helicobacter spp involved. More studies are therefore needed to confi rm whether a causal association exits between the presence of Helicobacter spp in the liver and the development of cirrhosis and hepatocellular carcinoma.
The journey from hepatitis to hepatocellular carcinoma Bridging role of Helicobacter species
Hepatocellular carcinoma (HCC) is a long-term consequence of chronic liver disease, whose aetiology could result from viral, environmental and hereditary causes. Viral infection, by itself, could only partially explain the pathogenesis of cirrhosis and HCC. A new aetiologic agent capable of inducing chronic active hepatitis and hepatocellular tumours was discovered: it is a bacterium belonging to the genus Helicobacter, and named H. hepaticus. Presence of sequences belonging to the 16S rRNA of Helicobacter species (spp.) has been demonstrated in liver of most patients with cirrhosis and HCC. H. pylori and related bacteria, such as H. hepaticus, produce toxins that kill hepatocyte by a granulating effect on liver cell lines. In vivo, such toxins might reach the liver through the portal tract, thereby causing hepatocellular damage. The recognition of Helicobacter spp. as a possible risk factor for cirrhosis and HCC might have a practical impact on the general population: the treatment of this infection is easy and far less expensive than liver transplantation or any long term treatment for the other risk factors of HCC. Any confirmation of the involvement of Helicobacter in liver disease would eventually come from the success of culturing the bacterium from liver tissues. Future research is needed to clarify the importance of Helicobacter spp. in respect to the other pathogens already known as causative agents of chronic inflammation of the liver and its long term sequelae, namely cirrhosis and HCC.
Helicobacter species and hepatobiliary diseases
Alimentary Pharmacology & Therapeutics, 2002
Helicobacter species, which may colonize the biliary tract, have been implicated as a possible cause of hepatobiliary diseases ranging from chronic cholecystitis and primary sclerosing cholangitis to gall-bladder carcinoma and primary hepatic carcinomas.Research in this area has been limited by the lack of a gold standard in the diagnosis of these organisms in bile. Most published data to date have been based on molecular techniques that detect the DNA of Helicobacter species in bile, rather than evidence of viable organisms in bile.Helicobacter species have not been shown to induce histological injury to the biliary epithelium or liver parenchyma. The strongest association of the presence of these organisms in bile is with cholestatic conditions. This article reviews the literature on this newly developing field as it has evolved historically, taking pertinent methodological issues into account.