In this review, we offer a concise overview of liver cancer epidemiology in China and worldwide from the official databases of GLOBOCAN 2020 and the National Cancer Registry in China. We also summarized the evidence for the main risk factors associated with liver cancer risk and discuss strategies implemented in China to control the liver cancer burden. Overall, liver cancer was the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. Although China contributed to nearly half of cases across the world alone, the incidence and mortality rates of liver cancer presented a declining trend owing to the persistent efforts from the governments at all levels. The current liver cancer burden in China still faces an arduous challenge due to the relatively large population base as well as the substantially low survival rate (12.1%). To better control the liver cancer burden with the lowest cost, specific measures should be conducted by reducing exposure to established risk factors such as hepatitis B infection and aflatoxin. The promotion of surveillance is also an important method to prolong the survival of liver cancer. This review will provide basic information for future direction on the control of liver cancer burden.

Burden of liver cancer: From epidemiology to prevention.

Abstract Background Sarcopenia is associated with unfavourable long‐term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. Methods Seven hundred fifty‐six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non‐sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre‐ and post‐LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence‐free survival (RFS). Results The study comprised 673 males and 83 females. The median follow‐up time was 31 months (interquartile range, 19–43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low‐SMI) and myosteatotic (low‐SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS ( P &lt; 0.001) and a 15.0% decrease in 5 year RFS ( P = 0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317–1.869; P &lt; 0.001] and RFS (HR, 1.369; 95% CI, 1.182–1.586; P &lt; 0.001). Postoperatively, a muscle loss &gt;14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358–3.849; P = 0.002) and RFS (HR, 2.219; 95% CI, 1.418–3.471; P &lt; 0.001) in non‐sarcopenic recipients ( N = 209). Conclusions Pre‐transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post‐transplant muscle loss might assist in prognostic stratification of recipients without pre‐existing sarcopenia, intriguing new insights into individualized management. 

Myosteatosis and muscle loss impact liver transplant outcomes in male patients with hepatocellular carcinoma

Objective
Circulating tumor DNA (ctDNA) and alpha-fetoprotein (AFP) plus ultrasound (US) have been considered to have high diagnostic accuracy for cancer detection, however, the efficacy of ctDNA methylation combined with the traditional detection modality of liver cancer has not been tested in a Chinese independent cohort.


Methods
The high-risk individuals aged between 35 and 70 years who were diagnosed with liver cirrhosis or had moderate and severe fatty liver were eligible for inclusion. All participants were invited to receive a traditional examination [referring to AFP plus US], and ctDNA methylation, respectively. The sensitivity and specificity of different diagnostic tools were calculated. The logistic regression model was applied to estimate the area under the curve (AUC), which was further validated by 10-fold internal cross-validation.


Results
A total of 1,205 individuals were recruited in our study, and 39 participants were diagnosed with liver cancer. The sensitivity of AFP, US, US plus AFP, and the combination of US, AFP, and ctDNA methylation was 33.33%, 56.41%, 66.67%, and 87.18%, respectively. The corresponding specificity of AFP, US, US plus AFP, and the combination of all modalities was 98.20%, 99.31%, 97.68%, and 97.68%, respectively. The AUCs of AFP, US, US plus AFP, and the combination of AFP, US, and ctDNA methylation were 65.77%, 77.86%, 82.18%, and 92.43%, respectively. The internally validated AUCs of AFP, US, US plus AFP, and the combination of AFP, US, and ctDNA methylation were 67.57%, 83.26%, 86.54%, and 93.35%, respectively.


Conclusions
The ctDNA methylation is a good complementary to AFP and US for the detection of liver cancer.

Efficacy of ctDNA methylation combined with traditional detection modality to detect liver cancer among high-risk patients: A multicenter diagnostic trial.

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide including sub-Saharan Africa. The GALAD score, derived from Gender, Age, Lens culinaris agglutinin-reactive fraction of alpha fetoprotein (AFP-L3%), AFP and Des-carboxy-prothrombin (DCP) has high accuracy in diagnosing HCC in Asia, Europe, and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in sub-Saharan Africa. Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from outpatient hepatology clinics at three teaching hospitals in Ghana were abstracted, and serum samples were analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval (CI) was calculated. The median GALAD score was higher among HCC patients vs. cirrhosis controls (8.0 vs. -4.1, p&amp;lt;0.01). The AUC of the GALAD score for HCC detection was 0.86 (95% CI 0.79 – 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. The AUC (95% CI) was 0.87 (0.80 – 0.95) and 0.81 (0.67 – 0.94) in HBV positive and HBV negative patients, respectively. The GALAD score has a high accuracy for HCC detection. It has great potential to improve HCC surveillance in sub-Saharan Africa where imaging resources are limited. 

GALAD score for the diagnosis of Hepatocellular Carcinoma in sub-Saharan Africa; a validation study in Ghanaian patients.

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66–0.79)) and a high specificity (0.87 (95%CI: 0.81–0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66–0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66–0.87), 0.80 (95%CI: 0.72–0.87), and 0.86 (95%CI: 0.83–0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality. 

/pdf/the-performance-of-galad-score-for-diagnosing-hepatocellular-3vezj8bw.pdf

The Performance of GALAD Score for Diagnosing Hepatocellular Carcinoma in Patients with Chronic Liver Diseases: A Systematic Review and Meta-Analysis

Objective Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults. Methods HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction. Results With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively. Conclusions Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.

/pdf/a-male-abcd-algorithm-for-hepatocellular-carcinoma-risk-194xoi0ph0.pdf

A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBsAg carriers.

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A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBsAg carriers.