Hepatitis B virus infection and hepatocellular carcinoma in sub- Saharan Africa: Implications for elimination of viral hepatitis by 2030?

Elimination of viral hepatitis in sub-Saharan Africa by 2030 is an ambitious feat.However,as stated by the World Health Organization,there are unprecedented opportunities to act and make significant contributions to the elimination target.With 60 million people chronically infected with hepatitis B virus(HBV)of whom 38800 are at risk of developing highly fatal hepatocellular carcinoma(HCC)every year,sub-Saharan Africa faces one of the greatest battles towards elimination of viral hepatitis.There is a need to examine progress in controlling the disproportionate burden of HBV-associated HCC in sub-Saharan Africa within the context of this elimination target.By scaling-up coverage of hepatitis B birth dose and early childhood vaccination,we can significantly reduce new cases of HCC by as much as 50%within the next three to five decades.Given the substantial reservoir of chronic HBV carriers however,projections show that HCC incidence and mortality rates in sub-Saharan Africa will double by 2040.This warrants urgent public health attention.The trends in the burden of HCC over the next two decades,will be determined to a large extent by progress in achieving early diagnosis and appropriate linkage to care for high-risk chronic HBV infected persons.

sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

BACKGROUND：The current methods used for diagnosing hepatocellular carcinoma（HCC）are unsatisfactory.Here,we assessed the serum levels of secreted frizzled related protein 4（s FRP-4）for diagnosing HCC in patients infected with chronic hepatitis B（CHB）.METHODS：In 272 patients with CHB enrolled,142 were pa tients with HCC.Thirty-three healthy subjects were recruited as healthy controls.The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients （8 CHB-related HCC patients, 7 CHB patients） for serum mark- ers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS： Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients （P〈0,05）. Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group （79.7 vs 41.3 ng/mL; P〈0.001） and validation group （89.0 vs 39.0 ng/mL; P〈0.001）. Areas under the Receiver Operating Charac- teristic curves （AUCs） for alpha-fetoprotein （AFP） and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 （a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL） and AFP （a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL） showed better performance for diagnosing HCC （a sensitivity of 79.2% and a specificity of 95.3%）. The AUC for combined sFRP-4 and AFP increased to 0.941 （95% CI： 0.908-0.975）, and similar results were seen in the validation group. CONCLUSION： sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.

Clinical significance of serum sB7-H3 and IL-1 in patients with hepatitis B related hepatocellular carcinoma

Objective: To explore the clinical significance of serum sB7-H3 and IL-1 in patients with hepatitis B associated hepatocellular carcinoma. Methods: 122 cases of patients with hepatitis B related liver diseases admitted to our hospital from January 2015 to June 2018 were selected, including 47 cases of patients with hepatitis B related hepatocellular carcinoma, 41 cases of patients with hepatitis B related cirrhosis and 34 cases of patients with hepatitis B virus, and 45 cases of healthy persons in the same period as normal control group. The serum sB7-H3, IL-1α, IL-1β levels were compared among the four groups. The relationship between serum sB7-H3, IL-1α, IL-1β and clinicopathological characteristics was analyzed, and the correlation of sB7-H3, IL-1α and IL-1β was analyzed by Pearson method. The efficacy of serum sB7-H3, IL-1α, IL-1β in early diagnosis and prognostic evaluation for hepatitis B associated hepatocellular carcinoma were analyzed by ROC and Logistic regression analysis. Results: The serum sB7-H3, IL-1α, IL-1β levels in the four groups were in order from high to low: hepatitis B related hepatocellular carcinoma>hepatitis B related cirrhosis>hepatitis B virus>normal control group, all above had statistical difference (P<0.05). The high levels of serum sB7-H3, IL-1α, IL-1β were significantly correlated with TNM stage, alpha fetoprotein level and lymph node metastasis (P<0.05). Spearman correlation analysis results showed that the serum level of sB7-H3 was positively correlated with IL-1α and IL-1β(r=0.837, 0.756;P<0.05), the serum level of IL-1α was positively correlated with IL-1β(r=0.734, P<0.05). The ROC curve and Logistic regression analysis showed that the AUC of sB7-H3, IL-1α, IL-1β and combined detection for the diagnosis of hepatitis B associated hepatocellular carcinoma was 0.893, 0.887, 0.881, 0.961 (P<0.05), respectively;the AUC of sB7-H3, IL-1α, IL-1β and combined detection for the prognostic evaluation for hepatitis B associated hepatocellular carcinoma was 0.843, 0.837, 0.834, 0.917, respectively. Conclusion:Serum sB7-H3, IL-1α, IL-1β levels could all be used for the early diagnosis and prognostic evaluation of hepatitis B associated hepatocellular carcinoma, and the combined detection is more effective, which has important clinical significance.

Liver Transplantation Outcomes of HBV-,HCV-,and Alcohol-induced Hepatocellular Carcinoma in the United States:Analysis of National Inpatient Samples

Objective Liver transplantation is a current treatment option for hepatocellular carcinoma(HCC).The United States National Inpatient Sample database was utilized to identify risk factors that influence the outcome of liver transplantation,including locoregional recurrence,distant metastasis,and in-hospital mortality,in HCC patients with concurrent hepatitis B infection,hepatitis C infection,or alcoholic cirrhosis.Methods This retrospective cohort study included HCC patients(n=2391)from the National Inpatient Sample database who underwent liver transplantation and were diagnosed with hepatitis B or C virus infection,co-infection with hepatitis B and C,or alcoholic cirrhosis of the liver between 2005 and 2014.Associations between HCC etiology and post-transplant outcomes were examined with multivariate analysis models.Results Liver cirrhosis was due to alcohol in 10.5%of patients,hepatitis B in 6.6%,hepatitis C in 10.8%,and combined hepatitis B and C infection in 24.3%.Distant metastasis was found in 16.7%of patients infected with hepatitis B and 9%of hepatitis C patients.Local recurrence of HCC was significantly more likely to occur in patients with hepatitis B than in those with alcohol-induced disease.Conclusion After liver transplantation,patients with hepatitis B infection have a higher risk of local recurrence and distant metastasis.Postoperative care and patient tracking are essential for liver transplant patients with hepatitis B infection.

Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples.Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P<0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3%,AP=0.80)and miR-16(AUC=0.83,79.0%,AP=0.83)than for AFP(AUC=0.74,61.7%,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9%)and the AP to 0.85 and was significantly superior to the other markers in this study(P<0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

Prognostic value of glypican-3 in patients with HBV-associated hepatocellular carcinoma after liver transplantation

BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.

Hepatic Resection Combined with Radiofrequency Ablation versus Hepatic Resection Alone for Multifocal Hepatocellular Carcinomas:A Meta-analysis

This meta-analysis aimed to comprehensively assess the efficacy and safety of hepatic resection combined with radiofrequency ablation versus hepatic resection（HR） alone for the treatment of multifocal hepatocellular carcinomas（HCC）. A literature search was conducted from the database including MEDLINE, Embase, Cochrane Central Register of Controlled Trials（CENTRAL） and China Biology Medicine（CBM） disc. The primary outcomes included the 1-, 3-, 5-year overall survival（OS） and disease-free survival（DFS） rate. The secondary outcomes contained the intraoperative parameters and postoperative adverse events（AEs）. These parameters were all analyzed by Rev Man 5.3 software. After carefully screening relevant studies, four retrospective studies of high quality involving 466 patients（197 in the combined group and 269 in the HR group） were included in this study. The pooled results showed that the 1-, 3-, 5-year OS rate in the combined group were comparable with those in the HR group（OR=0.77, 0.96, 0.88; P=0.33, 0.88, 0.70, respectively）. Similarly, there was no significant difference in 1-, 3-, 5-year DFS rate between the combined group and the HR alone group（OR=0.57, 0.83, 0.72; P=0.17, 0.37, 0.32, respectively）. And the intraoperative parameters and postoperative AEs were also comparable between the above two cohorts. However, two included studies reported that tumor often recurred in the ablation site in the combined group. The present meta-analysis indicated that the HR combined with RFA could reach a long-term survival outcome similar to curative HR for multifocal HCC patients. And this therapy may be a promising alternative for these patients with marginal liver function or complicated tumor distribution. Furthermore, high quality randomized controlled trials（RCTs） are imperative to verify this conclusion.

Hepatic Angiomyolipoma Demonstrating Similar Imaging Characteristics as Hepatocellular Carcinoma: One Case Report

Angiomyolipoma （AML） is a benign mesenchymal tumor that has been frequently reported in the kidney but rarely in the liver. AML is composed of fat, vascular, and smooth muscle elements. Because the proportion of the constituents composed of AML are varied, hepatic AML may be clinically, radiologically and morphologically difficult to distinguish from hepatocellular carcinoma （HCC） or other hepatic lesions. Here we report a case with pathologically confirmed hepatic AML who was previously diagnosed as HCC based on imaging examinations.

A Decade-old Change in the Screening Rate for Hepatocellular Carcinoma Among a Hepatitis B Virus-infected Population in Korea

Background： Evaluating a change in the screening rate for hepatocellular carcinoma （HCC） is critical for understanding screening implementation, and whether targeted population groups are receiving proper screening. This study examined recent nationwide changes in HCC screening use among hepatitis B virus （HBV）-infected populations after the introduction of the Korean National Cancer Screening Program and predictors of screening adherence. Methods： We analyzed 165 and 276 participants 〉40 years of age who were hepatitis B surface antigen-positive fiom 2001 （14,936 participants） to 2010-2011 （9159 participants） Korea National Health and Nutrition Examination Surveys, respectively. Demographic data, socioeconomic factors, and HCC screening use were collected by means of self-reported questionnaires. Results： The rate of HCC screening within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 2010- 20I 1 （P〈 0.0001 ）. The rate of HCC screening use increased from 2001 to 2010-2011 in all study populations. Subjects who had a higher income staius and were aware of their infection were more likely to have undergone recent HCC screening. Conclusions： This study showed a substantial increase in HCC screening in high-risk HBV-infected subjects from 2001 to 2010-2011. However, the HCC screening participation rate remained suboptimal despite the introduction of the nationwide screening program. Efforts should be made to identiry high-risk individuals and increase attendance at HCC screening events among high-risk groups.

Genotyping of Hepatitis C Virus in Patients with Hepatocellular Carcinoma.

Forty-two patients with hepatocellular carcinoma（HCC）were examined for hepatitis C virus（HCV）RNA in liver tissues by reverse transcription-polymerase chain reaction（RT PCR）.Typing of HCV liver samples of 18 patientswas dependent on the amplication of NSregion gy PCR using type-specific primers.