Impairment of cytochrome P‐450‐dependent liver activity in cirrhotic patients with Helicobacter pylori infection

Abstract

Background: Helicobacter pylori gastric infection has been associated with various digestive and extra‐digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function. Aims: To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P‐450 activity, and the 13C‐galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori‐associated modifications of liver function may be related to tumour necrosis factor‐α serum levels. Patients and methods: Thirty‐five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C‐galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti‐H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor‐α serum levels were then analysed on the basis of the presence of H. pylori infection. Results: Twenty‐one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori‐infected and non‐infected patients. H. pylori infection showed no difference in distribution according to Child–Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori‐positive patients compared to H. pylori‐negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C‐galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor‐α serum levels were no different between H. pylori‐positive (16.1 pg/mL, 95% confidence interval, 8.7–28.7) and H. pylori‐negative (12.3 pg/mL, 95% confidence interval, 8.7–23.4) patients. Conclusions: In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P‐450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor‐α does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.

Influence of 1-Week Helicobacter pylori Eradication Therapy with Rabeprazole, Clarithromycin, and Metronidazole on 13C-Aminopyrine Breath Test

“…This finding underscores that the minimal modifications in CYP-450 activity that occurred during treatment are completely reversible. Furthermore, since it is unlikely that H. pylori eradication may lead to an improvement in gastric emptying and/or increased absorption of aminopyrine (38)(39)(40), it should be interesting to evaluate in larger cohorts of patients whether H. pylori may affect CYP-450 activity as seems to happen in patients with chronic liver disease (41,42).…”

Prevalence of Helicobacter pylori Infection in Male Patients with Osteoporosis and Controls

“…Aromatase is a key enzyme in sex steroid biosynthesis, being responsible for conversion of C19 steroids to estrogens in a number of human tissues, including the liver (12,13). As some researchers have recently found that H. pylori infection selectively affects cytochrome P-450 liver activity (14), it is plausible that H. pylori-infected patients show diminished rates of conversion of steroids to estrogens. These researchers, however, did not differentiate CagA-seropositive and -seronegative patients; therefore, their findings cannot be applied tout course to our results, which showed that only CagA-seropositive osteoporotic patients had reduced systemic levels of estrogens.…”

Helicobacter pylori infection in hepatic encephalopathy: Relationship to plasma endotoxins and blood ammonia

“…Nevertheless, the exact mechanism of H. pylori endotoxins on different hepatic lesions is not known. In cirrhotic patients, H. pylori infection seems to affect cytochrome P450 liver activity selectively 35 . Helicobacter pylori LPS can provoke a microvascular inflammatory response and permeability in the rat cardiac, renal, hepatic and pulmonary tissues, actions mediated through the activation of the inducible nitric oxide synthase isoenzyme 36 .…”

“…In cirrhotic patients, H. pylori infection seems to affect cytochrome P450 liver activity selectively. 35 Helicobacter pylori LPS can provoke a microvascular inflammatory response and permeability in the rat cardiac, renal, hepatic and pulmonary tissues, actions mediated through the activation of the inducible nitric oxide synthase isoenzyme. 36 Thus, there is a potential capacity of H. pylori to damage the liver by producing toxins with a granulating effect on liver cell lines which, in vivo, through the portal tract, might reach the liver, thus causing hepatocellular damage.…”