Jin Bian

Association between proton pump inhibitors and hepatic encephalopathy: A meta-analysis

Background & aims: Several studies have shown that proton pump inhibitors (PPIs) use can increase the risk of developing hepatic encephalopathy (HE) in patients with liver dysfunction. However, no definite conclusion is drawn because of study design limitations. Therefore, we conducted a meta-analysis to explore the association between PPIs and HE. Methods: We searched PubMed, EMBASE, and the Cochrane Library from inception until November 2016. Data from the identified studies were combined using a random effects model, and odds ratios (ORs) were calculated. Results: Three case-control studies were included. Compared with nonusers, hepatic insufficiency patients receiving PPIs therapy had a significantly increased risk of developing HE (OR = 1.76, 95% CI: 1.15–2.69), with notable heterogeneity (I2 = 61.4%, P = .075) and publication bias. No relevance was found between PPIs and HE after using the trim and fill method (OR = 1.360, 95%CI: 0.909–2.035, P = .135). Conclusions: PPIs are associated with a higher risk of HE among patients with chronic and acute liver dysfunction. A final conclusion cannot be drawn because of the limited number of studies and a lack of prospective studies.

Whole-exome sequencing reveals the origin and evolution of hepato-cholangiocarcinoma

Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). To date, molecular mechanisms underlying the co-existence of HCC and iCCA components in a single tumor remain elusive. Here, we show that H-ChC samples contain substantial private mutations from WES analyses, ranging from 33.1 to 86.4%, indicative of substantive intratumor heterogeneity (ITH). However, on the other hand, numerous ubiquitous mutations shared by HCC and iCCA suggest the monoclonal origin of H-ChC. Mutated genes identified herein, e.g., VCAN, ACVR2A, and FCGBP, are speculated to contribute to distinct differentiation of HCC and iCCA within H-ChC. Moreover, immunohistochemistry demonstrates that EpCAM is highly expressed in 80% of H-ChC, implying the stemness of such liver cancer. In summary, our data highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.Hepatocellular-cholangiocarcinoma (H-ChC) is a rare subtype of liver cancer with features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Here, the authors utilize whole exome sequencing to highlight the monoclonal origin and stemness of H-ChC, as well as substantial intratumoral heterogeneity.

Brain metastases from hepatocellular carcinoma: recent advances and future avenues

The incidence of brain metastases from hepatocellular carcinoma (BMHCC) is becoming more frequent than that of the past as a result of prolonged survival of patients with HCC. Compared with brain metastases from other types of cancer, BMHCC tends to exhibit a high incidence of intracerebral hemorrhage (ICH) and poor liver function. Unfortunately, the prognosis is extremely poor for patients with BMHCC owing to the limited treatment selection. Currently, optimal treatment requires multidisciplinary approaches including surgery, whole-brain radiation therapy and stereotactic radiosurgery. Besides these traditional approaches, novel treatments such as target therapy and immunotherapy provide an opportunity to improve the survival of these patients. This review provides an overview of the incidence, characteristics, prognosis, and current and potential future management strategies for BMHCC.

Hepatitis B virus infection and the risk of nonalcoholic fatty liver disease: a meta-analysis

Some studies have reported that hepatitis B virus (HBV) infection affects the risk of nonalcoholic fatty liver disease (NAFLD). However, this association is controversial. We conducted a systematic review and meta-analysis to investigate the relationship between HBV infection and NAFLD. Relevant studies published before May 2017 were identified by searching PubMed, EMBASE, and ISI Web of Science. We used the random-effects model proposed by DerSimonian and Laird to quantify the relationship between HBV infection and risk of NAFLD. We also conducted subgroup and sensitivity analyses to validate the stability of the results. Five articles, comprising 8,272 HBV-infected patients and 111,631 uninfected controls, were included in our research. Our meta-analysis suggested that the risk of NAFLD was significantly lower in HBV-infected patients than in uninfected controls, with heterogeneity between studies (summary odds ratio [OR] = 0.71; confidence interval [CI] = 0.53–0.90; I2 = 75.2%). However, the inverse relationship was observed in only cohort (OR = 0.83; 95% CI = 0.73–0.94) and cross-sectional studies (OR = 0.63; 95% CI = 0.47–0.79), not case-control studies (OR = 3.96; 95% CI = 2.10–7.48). In conclusion, HBV infection was inversely associated with the risk of NAFLD.

Hypertension and risk of cholangiocarcinoma: a systematic review and meta-analysis

Background: Hypertension has been demonstrated to enhance the risk of cholangiocarcinoma (CCC) by several researches, which, however, still remains controversial. To this end, a systematic review and meta-analysis was performed to further investigate the association between hypertension and CCC risk. Methods: We searched PubMed, EMBASE, ISI Web of Science to collect relevant researches published before November 2017. Afterwards, random effects model proposed by DerSimonian and Laird was employed to determine the correlation between hypertension and CCC risk. Results: Nine articles, comprising 2,016 patients with CCC and 199,812 healthy controls, were finally enrolled in our study. Our findings failed to support the correlation between hypertension and elevated risk of CCC among these heterogeneous studies [summary odds ratio (OR), 0.87; 95% confidence interval (CI), 0.57–1.17; I 2 =79.5%]. In subgroup analysis following separation of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), hypertension also failed to harbor a correlation with elevated risk of ECC (OR, 0.74; 95% CI, 0.42–1.37) and ICC (OR, 1.07; 95% CI, 0.43–1.71). Conclusions: Hypertension did not harbor any correlation with elevated risk of CCC.

Metabolic syndrome and the risk of cholangiocarcinoma: a hospital-based case–control study in China

Background Metabolic syndrome is regarded as a risk factor for hepatocellular carcinoma. However, no research has been conducted to investigate the association between metabolic syndrome and cholangiocarcinoma (CCA), especially in the Chinese population. Herein, a hospital-based case–control study was carried out in China to explore the association between metabolic syndrome and CCA risk. Patients and methods In this study, 303 CCA patients (136 intrahepatic cholangiocarcinoma [ICC] and 167 extrahepatic cholangiocarcinoma [ECC]) were included, who were observed at Peking Union Medical College Hospital (PUMCH), from 2002 to 2014. Healthy controls were randomly selected from the database of PUMPH Health Screening Center. We retrospectively extracted metabolic syndrome and other possible risk factors from clinical records, followed by investigation of the relationship with CCA via calculation of ORs and 95% CIs using logistic regression analysis. Results Metabolic syndrome was significantly and positively correlated with all CCA subtypes, with adjusted ORs (AORs) of 0.35 (95% CI =0.29–0.42) and 0.29 (95% CI =0.19–0.44) for ICC and ECC, respectively (both P<0.001). Dyslipoproteinemia harbored a stronger relationship with ICC (OR =3.16; 95% CI =2.12–4.71) than ECC (OR =1.87; 95% CI =1.27–2.77), whereas hypertension harbored a stronger association with ECC (OR =3.09; 95% CI =2.09–4.58) than ICC (OR =2.06; 95% CI =1.32–3.21). Obesity was related to both ICC and ECC, with similar ORs, while diabetes was only related to ICC (OR =4.59; 95% CI =2.78–7.58), but not ECC (OR =0.97; 95% CI =0.49–1.94). Conclusion Metabolic syndrome was significantly related to a 1.86-fold elevated CCA risk.

Aspirin use is associated with a reduced risk of cholangiocarcinoma: a systematic review and meta-analysis

Background Aspirin has been revealed to probably decrease the risk of cholangiocarcinoma (CCC), which, nevertheless, is of controversy. To this end, a systematic review and meta-analysis was performed to investigate the above-described association. Methods We thoroughly searched PubMed, EMBASE, and ISI Web of Science for relevant studies published prior to October 2017, followed by random-effects model for calculation of pooled ORs and corresponding 95% CIs. Additionally, subgroup and sensitivity analyses were carried out to confirm whether the outcomes were stable. Results Nine articles, consisting of 12,535 CCC patients and 92,97,450 healthy controls, were enrolled in this study. We demonstrated a significantly decreased risk of CCC in those using aspirin, with studies being heterogeneous (OR=0.69; CI=0.43–0.94; I2=97.4%). Moreover, this relationship was detected only in case-control studies (OR=0.65; 95% CI=0.38–0.93), rather than cohort studies (OR=0.94; 95% CI=0.70–1.27). Besides, in separated analysis of intrahepatic CCC and extrahepatic CCC, aspirin was more strongly correlated with a declined risk of intrahepatic CCC (OR=0.33, 95% CI=0.26–0.39; I2=93.6%) than the risk of extrahepatic CCC (OR=0.56, 95% CI=0.41–0.73; I2=0%). Conclusion Collectively, the aspirin administration was correlated with a significant 31% decreased risk of CCC, particularly in the intrahepatic CCC.

Erratum to comparison of portal vein embolization, portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy in cases with a small future liver remnant: a network meta-analysis

Comparison of portal vein embolization, portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy in cases with a small future liver remnant: a network meta-analysis

Systematic review and meta-analysis: cholecystectomy and the risk of cholangiocarcinoma

Studies have reported that cholecystectomy may increase the risk of cholangiocarcinoma. However, this association is controversial. Thus, we conducted a systematic review and meta-analysis to explore the relationship between cholecystectomy and the risk of cholangiocarcinoma. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science published before February 2017. We used the random effects model proposed by DerSimonian and Laird to quantify the relationship between cholecystectomy and risk of cholangiocarcinoma. Publication bias was evaluated using funnel plots, Beggs and Eggers tests. Subgroup and sensitivity analyses were performed to validate the stability of the results. 16 articles, comprising 220,376 patients with cholecystectomy and 562,392 healthy controls, were included in our research. Our meta-analysis suggested that the risk of cholangiocarcinoma was significantly higher in the cholecystectomized patients in comparison with healthy controls, with heterogeneity among studies (summary odds ratio [OR] = 0.72; confidence interval [CI] = 0.55–0.90; I2 = 69.5%). Additionally, this association was also observed in cohort studies (OR = 0.83; 95% CI = 0.73–0.94) and case-control studies (OR = 0.60; 95% CI = 0.40–0.80). However, When the intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma were analyzed separately, the present study only indicated cholecystectomy was associated with increased the risk of extrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32–2.05), rather than intrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32–2.05). In conclusion, cholecystectomy was associated with a significant 54% increase in the risk of cholangiocarcinoma, especially in the extrahepatic cholangiocarcinoma.