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Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33–55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26–40.75). Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI. [Display omitted] • BMI, WC, WHR, WHtR, and HC were, respectively, positively associated with the risk of PLC. • Elevated WC, independent of BMI, was associated with an increased risk of PLC. • The incidence of PLC was higher in central adiposity than that in general adiposity. • WC might be a more promising predictive indicator for PLC beyond BMI. [ABSTRACT FROM AUTHOR]

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC. [ABSTRACT FROM AUTHOR]

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. The review was not registered. [ABSTRACT FROM AUTHOR]

Background: The relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy. Methods: All associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias. Results: Thirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521). Conclusions: High baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: The role of hypoxia‐inducible factor‐1α (HIF‐1α) and hypoxia‐inducible factor‐2α (HIF‐2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF‐1α and HIF‐2α overexpression with the prognosis and clinicopathological features of HCC. Methods: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta‐analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease‐free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. Results: Twenty‐two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF‐1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53–2.00)] and DFS [HR = 1.64 (95% CI: 1.34–2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36–2.48)], tumor size [OR = 1.36 (95% CI: 1.12–1.66)], and tumor number [1.74 (95% CI: 1.34–2.25)]. In contrast, HIF‐2α overexpression was not associated with the prognosis and clinicopathological features of HCC. Conclusion: Our data provided compelling evidence of a worse prognosis of HCC in HIF‐1α overexpression patients but not HIF‐2α overexpression ones. [ABSTRACT FROM AUTHOR]

• Hepatocellular carcinoma patients with impaired liver function have poor prognosis after receiving ICIs. • Both ALBI score and Child-Pugh score can stratify HCC patients. • ALBI score is simpler and more reliable for patient stratification than Child-Pugh score. • The incidence of adverse events is not significantly increased in impaired liver function patients. Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs. Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS). 41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR = 2.01,95 %CI:1.69–2.38; PFS:HR = 1.39,95 %CI:1.15–1.68) or albumin-bilirubin (ALBI) score (OS:HR = 2.04,95 %CI:1.55–2.69; PFS:HR = 1.42,95 %CI:1.21–1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR = 1.69,95 %CI:1.26–2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function. Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications. [ABSTRACT FROM AUTHOR]