Helicobacter Species and Hepato-Biliary Tract Malignancies: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Chronic infections are major drivers of cancer. Helicobacter species is one of the most established pro-oncogenic pathogens, but its relationship with hepatobiliary tract malignancies is controversial. We performed a systematic review and meta-analysis of 26 observational studies, including 1203 patients with hepatobiliary tract malignancies and 2880 controls. Helicobacter species chronic infection demonstrated by direct microbiological methods tripled the risk of hepatobiliary tract malignancies, and this effect was consistent for different types of specimens tested, including bile, gastric tissue, hepatic/biliary tissue, and serum. However, available studies were heterogeneous, and the overall quality of the evidence was low, translating into a grade of uncertainty. Prospective studies, randomized, if possible, are required to delineate interventions at a public healthcare scale, particularly in geographic areas with increased incidence of hepatobiliary tumors. ABSTRACT: Helicobacter species may cause chronic inflammation of the biliary tract, but its relationship with cancer is controversial. We performed a systematic review and meta-analysis to evaluate the association between Helicobacter species and hepatobiliary tract malignancies. Twenty-six studies (4083 patients) were included in qualitative synthesis, and 18 studies (n = 1895 qualified for meta-analysis. All studies were at high-intermediate risk of bias. Most studies combined several direct microbiological methods, mostly PCR (23 studies), culture (8 studies), and/or CLOtest (5 studies). Different specimens alone or in combination were investigated, most frequently bile (16 studies), serum (7 studies), liver/biliary tissue (8 studies), and gastric tissue (3 studies). Patients with Helicobacter species infection had an increased risk of hepatobiliary tract malignancies (OR = 3.61 [95% CI 2.18–6.00]; p < 0.0001), with high heterogeneity in the analysis (I(2) = 61%; p = 0.0003). This effect was consistent when Helicobacter was assessed in bile (OR = 3.57 [95% CI 1.73–7.39]; p = 0.0006), gastric tissue (OR = 42.63 [95% CI 5.25–346.24]; p = 0.0004), liver/biliary tissue (OR = 4.92 [95% CI 1.90–12.76]; p = 0.001) and serum (OR = 1.38 [95% CI 1.00–1.90]; p = 0.05). Heterogeneity was reduced in these sub-analyses (I(2) = 0–27%; p = ns), except for liver/biliary tissue (I(2) = 57%; p = 0.02). In conclusion, based on low-certainty data, Helicobacter species chronic infection is associated with a tripled risk of hepatobiliary tract malignancy. Prospective studies are required to delineate public health interventions.