Yang, Ju Dong

AbstractBackground & AimsAlthough hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC.MethodsWe conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878).ResultsCirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV‐related HCC (HBV‐HCC) (P = .001) and 85.9% of HCV‐HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five‐year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV‐HCC patients and 27.7% among HCV‐HCC patients (P < .001 for both by the log‐rank test). HCC aetiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were.ConclusionsCompared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumours at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease.

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109/L were matched with 97 of 119 patients who had preoperative PLT >75 × 109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow‐up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] = 3.09; 95% confidence interval [CI], 1.86‐5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23‐3.60; P = 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36‐4.01; P = 0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02‐3.54; P = 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha‐fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation‐based scores including neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and the inflammation‐based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation. Liver Transplantation 24 44–55 2018 AASLD.

Abstract Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways. The protein kinase A/cyclic AMP signaling pathway was altered frequently in mouse and human steatosis-associated HCC. We found that activated PKA expression drove steatosis-specific liver tumorigenesis in a mouse model. Another candidate HCC driver, the N-acetyltransferase NAT10, which we found to be overexpressed in human steatosis–associated HCC and associated with decreased survival in human HCC, also drove liver tumorigenesis in a steatotic mouse model. This study identifies genes and pathways promoting HCC that may represent novel targets for prevention and treatment in the context of hepatic steatosis, an area of rapidly growing clinical significance. Cancer Res; 77(23); 6576–88. ©2017 AACR.

Gallbladder cancer is a rare malignancy in most countries. The racial and sociodemographic factors associated with its incidence and survival are poorly defined. We aimed to investigate population-based gallbladder cancer incidence and survival trends on the basis of clinical characteristics and sociodemographic factors in the USA. Gallbladder cancer incidence and survival data from 2001 to 2012 were obtained from 18 registries of the Surveillance, Epidemiology, and End Results database. Incidence rates and Joinpoint trends were calculated by demographic subgroup. Survival trends were assessed using Cox proportional hazard models. A total of 7769 patients were identified. The overall gallbladder cancer incidence rates did not significantly change during the 2001–2012 period. Incidence rates were three times higher in Hispanics and 1.6 times higher in Blacks compared with Whites. Over the time period, incidence rates significantly increased among Blacks and decreased among Hispanics. Male sex [hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.03–1.17], older age (HR: 1.73, 95% CI: 1.53–1.96), and single and divorced statuses (HR: 1.19, 95% CI: 1.09–1.30 and 1.12, 95% CI: 1.01–1.24) were independently associated with shorter overall survival, whereas higher education (HR: 0.89, 95% CI: 0.82–0.97) and higher income (HR: 0.89, 95% CI: 0.82–0.96) were associated with longer survival. Furthermore, overall survival has improved in all races/ethnicities except for Hispanics and Blacks. The overall incidence rates for gallbladder cancer were stable during 2001–2012. Hispanics have the highest incidence rates, but the incidence rates in Blacks are on the rise.

AbstractBackground & AimsHepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America.MethodsWe evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations.ResultsSixty‐eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV‐related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01).ConclusionsOur study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients.

Objective: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. Background: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. Methods: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. Results: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. Conclusions: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Summary Hepatitis B virus ( HBV ) infection in the United States is the most common among Asians followed by non‐Hispanic blacks. However, there have been few studies that describe HBV infection and immunity by racial group. Our study aimed to assess racial/ethnic disparities in the prevalence and awareness of HBV infection and immunity using nationally representative data. In the National Health and Nutrition Examination Survey 2011‐2014, 14 722 persons had HBV serology testing. We estimated the prevalence of HBV infection, past exposure, and immunity by selected characteristics and calculated adjusted odds ratios using survey‐weighted generalized logistic regression. Awareness of infection and vaccination history was also investigated. The overall prevalence of chronic HBV infection, past exposure and vaccine‐induced immunity was 0.34% [95% CI 0.24‐0.43], 4.30% [95% CI 3.80‐4.81], and 24.4% [95% CI 23.4‐25.4], respectively. The prevalence of chronic infection was 2.74% [95% CI 1.72‐3.76] in Asians, 0.64% [95% CI 0.35‐0.92] in non‐Hispanic blacks, and 0.15% [95% CI 0.06‐0.24] in non‐Asian, non‐blacks. Only 26.2% of those with chronic infection were aware of their infection. The prevalence of the past exposure was 21.5% [95% CI 19.3‐23.7] in Asians, 8.92% [95% CI 7.84‐9.99] in non‐Hispanic blacks, 2.05% [95% CI 1.49‐2.63] in non‐Hispanic whites and 4.47% [95% CI 3.25‐5.70] in Hispanics. Prevalence of vaccine‐induced immunity by each race was 34.1% [95% CI : 32.0‐36.2] in Asians, 25.5% [95% CI : 24.0‐27.0] in non‐Hispanic blacks, 24.0% [95% CI : 22.6‐25.4] in non‐Hispanic whites and 22.2% [95% CI : 21.3‐23.3] in Hispanics. There are considerable racial/ethnic disparities in HBV infection, exposure and immunity. More active and sophisticated healthcare policies on HBV management may be warranted.

Background/Aim: The epidemiology of hepatocellular carcinoma (HCC) has changed in the United States recently. The aim of this study is to evaluate the recent trends of HCC epidemiology in Olmsted County, MN. Methods: Residents aged over 20 with newly diagnosed HCC were identified using the Rochester Epidemiology Project database. Clinical information was compared among patients diagnosed between 2000 and 2009 (era 1) and 2010 to 2014 (era 2). Results: Over 1.6 million person years of follow-up, 93 residents were diagnosed with HCC. The mean age was 67 and 71% were male. The age-adjusted and sex-adjusted incidence rates were 6.3 and 7.0 per 100,000 person years in the first and second eras (P=0.64). The proportion with hepatitis B virus etiology increased from 4% to 21% between the 2 eras (P<0.01), whereas there was a trend toward a decreasing proportion of hepatitis C virus etiology from 42% to 29% (P=0.20). Only 39% of HCC surveillance candidates had HCCs detected under surveillance and 41% of cirrhotic patients had unrecognized cirrhosis at the time of HCC diagnosis. Nonalcoholic fatty liver disease was associated with unrecognized cirrhosis and absence of cirrhosis at HCC diagnosis. More than half (56%) of patients presented at Barcelona Clinic Liver Cancer stage C or D and the median survival was 9.7 months. The overall survival had not changed over time. Conclusions: The incidence of HCC remained stable after 2010 in Olmsted County. The proportion of hepatitis B virus-induced HCC increased, whereas there was a trend of decreasing proportion of hepatitis C virus-induced HCC. The overall survival in community residents with HCC remains poor.