Surgery is considered the standard curative treatment option for hepatocellular carcinoma (HCC). However, the rate of long-term disease-free survival after liver resection remains unsatisfactory due to persistent high incidences of HCC recurrence.¹ Many factors affect HCC recurrence risk after liver resection, including tumor size and stage, serum α-fetoprotein level, cirrhosis, hepatitis B e antigen (HBeAg) status, and hepatitis B virus (HBV) viral load.^2-4 Among these factors, HBV viral load is the most clinically controllable.

Objective: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). Methods: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. Results: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori . Conclusion: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori . Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

The Asia–Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long‐established indications, such as peptic ulcer disease, early mucosa‐associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long‐term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population ‘test and treat’ strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long‐term aspirin or non‐steroidal anti‐inflammatory drug therapy in patients at high risk for ulcers and ulcer‐related complications. In Asia, the currently recommended first‐line therapy for H. pylori infection is PPI‐based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth‐based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI‐based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first‐line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth‐based quadruple therapy; (iii) levofloxacin‐based triple therapy; and (iv) rifabutin‐based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.

Objective Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective. Design In the nationwide case-control study, the authors recruited 97 430 HCC patients and 194 860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines. Results The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo. Conclusions Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase.