**6. Liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCC)**

Inflammation of gastric mucosa is a frequent complication of liver cirrhosis. Usually, occurrence of chronic inflammation is observed, described as portal gastropathy. *H. pylori* infection in the group of patients with liver cirrhosis impacts exacerbation of inflammatory changes in the stomach, which in turn worsens liver function. This is especially dangerous among patients with advanced liver injury. Studies performed on this group of patients point to high significance of cytopathic effect of *H. pylori* onto hepatocytes [16, 35]. *H. pylori* infection affects increase of portal tension, which is one of the main etiologies of development of esophageal varices [6, 36]. In effect, correlation between the frequency of *H. pylori* infection and advancement of esophageal varices is observed [37].

Evaluation of *H. pylori* infection among patients with chronic HCV infection is difficult. Some authors state that the frequency of *H. pylori* infection among the patients in this group is about 38%. Around 45% of those result from CagA-synthesizing bacteria. No significant differences are found in the morphological picture of HCV-infected liver, between patients with or without *H. pylori* infection. There is also no correlation between *H. pylori* infection and IL 28B polymorphism [22]. However, many other authors present other observations. *H. pylori* infection may be present in even 70% of patients chronically infected with HCV [23]. Meta-analysis of 20 studies demonstrated higher incidence of *H. pylori* infection among HCV-positive patients, compared to persons without viral infection [17, 24]. Much higher fibrosis, loss of cellular proteins, and glycogen was found in morphological studies of the liver from HCV-positive patients, if those were coinfected with *H. pylori*, compared to those without coinfection [25]**.**

Studies performed among patients with chronic viral autoimmune and toxic hepatitis and coexisting *H. pylori* infection demonstrated improvement in liver function, including

*H. pylori* infection is found in 20–50% of patients with AIH. Among patients with PBC, *H. pylori* infection is found more frequently than among people from the control group (54 vs. 31% p = 0.01). However, the effect of this infection on the course of PBC has not been eluci-

Infection by these bacteria worsens the course of underlying disease; however, pathogenesis is not completely clear [28, 29]. In the group of patients with PBC and AIH, *H. pylori* infection

Reports on the effect of *H. pylori* infection on lipid turnover disturbances, leading to hypertriglyceridemia and hypercholesterolemia with concomitant decrease of HDL level, are published more and more frequently. This is especially important for the metabolism of hepatocytes and their steatosis, as well as in the process of liver fibrosis [31]. Many reports point to the fact that *H. pylori* infection hastens the development of NAFLD [32]. It has been demonstrated that *H. pylori* infection among patients with NAFL results in the development of NASH. Eradication of the bacteria significantly facilitates the treatment of liver steatosis [33]. Moreover, it has been found that *H. pylori* infection and steatosis constitute the risk of

Inflammation of gastric mucosa is a frequent complication of liver cirrhosis. Usually, occurrence of chronic inflammation is observed, described as portal gastropathy. *H. pylori* infection in the group of patients with liver cirrhosis impacts exacerbation of inflammatory changes

decreased ALT and AST activity, after effective eradication of bacteria [26].

may lead to precipitous, unfavorable progression of the disease [30].

more frequent occurrence of cholecystolithiasis and choledocholithiasis [34].

**6. Liver cirrhosis, hepatocellular carcinoma (HCC), and** 

**cholangiocarcinoma (CCC)**

**5. Autoimmune diseases and liver steatosis**

50 Helicobacter Pylori - New Approaches of an Old Human Microorganism

dated [27].

Although in some studies more frequent *H. pylori* infection among patients with liver cirrhosis cannot be confirmed [38]; however, meta-analysis was performed that included mainly patients with alcoholic liver cirrhosis, which argues for much more frequent occurrence of these bacteria among such patients. *H. pylori* infection is much more frequent among patients with postinflammatory liver cirrhosis (connected with HBV or HCV infection) [37]. Incidence of *H. pylori* infection among patients with liver cirrhosis and concomitant HCV infection increases proportionally to progressing liver failure [39]. Moreover, it has been demonstrated that the highest percentage of people infected with *H. pylori* among those with HCV infection is observed in the case of patients in whom HCC developed [17, 24]. Many pieces of information argue that concomitant infection with *H. pylori* and HCV increases the incidence of HCC. Eradication of these bacteria in patients with cirrhotic liver leads to the increase of platelet count and improves efficacy of antiviral therapy [23, 40]. In the current setting, when direct-acting antivirals are commonly used, this is probably not so important; however, such studies have not been performed.

*H. pylori* catalyzes the reaction of urea decomposition to ammonia and carbon dioxide; however, among patients with subclinical hepatic encephalopathy, infection with these bacteria does not change the concentration of ammonia in the blood [41]. These observations are inconsistent, because among patients with liver cirrhosis, especially postinflammatory cirrhosis, more frequent occurrence of symptomatic hepatic encephalopathy with hyperammonemia is observed in the case of patients infected with *H. pylori*, compared to patients without this infection [37, 42]. In the studies performed in patients with liver cirrhosis, a correlation between increasing ammonia blood concentration and *H. pylori* infection has been demonstrated. Moreover, ammonia blood concentration was higher among patients with liver cirrhosis infected with *H. pylori*, compared to patients not infected with these bacteria [37].

In experimental studies performed on dogs, an association between *H. pylori* infection and occurrence of hepatocellular carcinoma (HCC) has been evidenced [43]. Evaluation of the effect of *H. pylori* infection on liver carcinogenesis in humans shows that in 58% of patients with HCC and in 62% of patients with CCC in the liver tissue surrounding focal lesion, DNA of these bacteria can be detected [44]. *H. pylori* may disturb the balance between hepatocyte proliferation and activity of apoptosis in the liver. In effect, there is a higher risk of occurrence of neoplastic cells in the liver [45].

In the pathogenesis of biliary duct carcinoma, *H. pylori* infection affects proliferation of biliary duct epithelium and development of inflammatory reaction in these cells. Activation of reactive oxygen species (oxidative stress) and reactive nitrogen species, mainly 8-nitroguanine, in the cells is detected. These reactions damage DNA of stem cells, playing a key role in carcinogenesis [46]. A special role in the development of bile duct carcinoma is attributed to *H. pylori* producing CagA toxin [47].
