Hepatocellular Carcinoma Related Mortality Research Articles

Availability of primary care physicians and hepatocellular carcinoma-related mortality in the United States.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer worldwide and majority cases are diagnosed at an intermediate or advanced stage. Per our analysis, greater availability of primary care physicians correlates with lower HCC-related mortality. Our results underscore the need for efforts to expand access to primary care among all populations, especially African Americans, to improve overall HCC-related outcomes.

S1556 Impact of Availability of Primary Care Physicians and Racial Disparities in Hepatocellular Carcinoma-Related Mortality in the United States

S1556 Impact of Availability of Primary Care Physicians and Racial Disparities in Hepatocellular Carcinoma-Related Mortality in the United States

Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.

African Immigrants in New York City with Hepatitis B-Related Hepatocellular Carcinoma Demonstrate High Morbidity and Mortality.

Guidelines recommend hepatitis B (HBV) testing in individuals from endemic areas, and if positive, screening for hepatocellular carcinoma (HCC). While screening programs are well established in the Asian immigrant population in New York City (NYC), less is known about the characteristics of HBV/HCC among the African immigrant community. A retrospective review was performed of HCC cases from 2005 to 2018 at our institution. Country of origin was not documented in the electronic medical record; therefore, African immigrant status was approximated using self-identified race/ethnicity, positive HBV status, and an online registry to determine country of origin based on last name. Surnames with the greatest prevalence or density in an African country were considered. Among 4400 patients with HCC, 472 identified as non-Hispanic Black; of these, 86 were HBV+. Based on surname, it was estimated that 33 individuals were likely immigrants from Africa. In this group, median age of HCC diagnosis was 48years (IQR 43-55). In patients with an available date of HBV diagnosis (n = 24), 17 (71%) were unaware of their HBV status when they presented with HCC. Zero patients were diagnosed with HCC through routine screening, most patients (66%) were diagnosed upon imaging evaluation of symptoms. Twelve patients (36%) underwent resection or transplantation; the remaining 64% were ineligible for surgical treatment. Of the 26 patients with follow-up data, 18 (69%) died of disease or were critically ill at last encounter, and of these, 14 (77%) died within 1 year of HCC diagnosis. In conclusion,African immigrants in NYC with HBV/HCC are at high risk of HCC related mortality ata young age. Mostwere unaware of their hepatitis statusat the time of HCC diagnosis. No patients were enrolled in routine HCC screening; the majority were diagnosed based on imaging obtained for symptoms. Most individuals presented with inoperable disease, and the majority died within months of diagnosis. Awareness of these findings may help healthcare providers improve patient outcomes.

Cost-Effectiveness Analysis of Antiviral Therapy for Untreated Minimally Active Chronic Hepatitis B to Prevent Liver Disease Progression.

INTRODUCTION:Antiviral therapy (AVT) for chronic hepatitis B (CHB) can prevent liver disease progression. Because of its stringent reimbursement criteria, significant numbers of patients with untreated minimally active (UMA)-CHB exist, although they are still subject to disease progression. We thus performed a cost-effectiveness analysis to assess the rationale for AVT for UMA-CHB.METHODS:We compared cost and effectiveness (quality-adjusted life years, QALYs) in virtual UMA-CHB cohorts of 10,000 50-year-olds receiving AVT (scenario 1) vs no treatment (scenario 2) for 10 years. A Markov model, including 7 health states of CHB-related disease progression, was used. Values for transition probabilities and costs were mostly obtained from recent South Korean data.RESULTS:The simulation of AVT vs no treatment predicted $2,201 incremental costs and 0.175 incremental QALYs per patient for 10 years, with an incremental cost-effectiveness ratio (ICER) of $12,607/QALY, suggesting cost-effectiveness of AVT. In sum, if 10,000 patients received AVT, 720 incident hepatocellular carcinoma and 465 CHB-related more deaths could be averted in 10 years relative to no treatment. When the simulated analysis period was extended to 20 years, AVT was also highly cost-effective with an ICER of $2,036/QALY. Although hepatocellular carcinoma–related mortality was a major factor influencing ICER, its fluctuation can be accepted within willingness to pay of $33,000 in South Korea. According to probabilistic sensitivity analysis with the threshold of willingness to pay, the probability of AVT cost-effectiveness was 83.3%.DISCUSSION:Long-term AVT for patients with UMA-CHB may contribute positively toward individual clinical benefit and national health care budget.

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B

Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.

Screening for hepatocellular carcinoma in chronic liver disease: a systematic review and meta-analysis of randomized controlled trials comparing screening methodologies

Background Globally, hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second most common cause of cancer-related mortality. HCC is often asymptomatic until an advanced stage. Current guidelines recommend ultrasound surveillance with or without measurement of serum alpha-fetoprotein. Our objective was to determine if screening for HCC is beneficial or harmful in patients with chronic liver disease. Primary outcomes were all-cause mortality and quality of life. Secondary outcomes were mortality due to HCC, the number of cases of HCC detected, and adverse events. Methods This is a systematic review and meta-analysis of data from randomized controlled trials. To be included trials had to randomize patients to either an HCC screening group or non-screening group, randomize patients to different screening frequencies or randomize patients to different screening methods. All published reports of randomized trials on screening for HCC were eligible for inclusion, irrespective of the language of publication. Studies had to include patients with chronic liver disease. Data extraction were performed independently by two reviewers. Results When screening with six-monthly alpha-fetoprotein and ultrasound abdomen was compared to no screening there was no evidence of difference in HCC related mortality when adjusted for clustering across a range of intracluster correlation coefficients (Intracluster coefficient (ICC) 0.02, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.31-1.15). Screening with six-monthly alpha-fetoprotein when compared to a single alpha-fetoprotein check did not result in a statistically significant difference in all-cause mortality (OR 1.02, 95% confidence interval (CI) 0.65-1.60), mortality due to HCC (OR 1.01, 95% CI 0.57-1.78) or the number of HCC detected (OR 1.11 95% CI 0.64-1.92). There was no evidence of difference in all-cause mortality (OR 0.81, 95% CI 0.26-2.53), mortality due to hepatocellular carcinoma (OR 0.81, 95% CI 0.26-2.53) or the number of patients with HCC detected (OR 1.09 95% CI 0.40-2.99) when twice-a-year ultrasound was compared with annual CT. There was no statistically significant difference when screening more frequently was compared to less frequently in terms of all-cause mortality (OR 0.86, 95% CI 0.56-1.32), mortality due to hepatocellular carcinoma (OR 1.42, 95% CI 0.55-3.64) and the number of cases of hepatocellular carcinoma detected (OR 0.90 95% CI 0.47-1.71). Conclusion There is currently insufficient evidence from randomized controlled trials to support routine screening for HCC in patients with chronic liver disease.

Concomitant Inhibition of Cytoprotective Autophagy Augments the Efficacy of Withaferin A in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality, and despite recent advances in early diagnosis and therapeutics, HCC related morbidity and mortality rate continue to rise. Clearly, it is imperative to develop novel effective therapies for HCC to improve long-term survival of HCC patients. We found that Withaferin A (WFA), a bioactive compound derived from Withania somnifera, is an effective agent for HCC inhibition. Interestingly, we observed that in addition to inducing apoptotic cell death, WFA also induces autophagy in HCC cells. Utilizing mRFP-EGFP-LC3B, LC3B-GFP/Lysotracker and LC3B-GFP/Rab7-RFP, we show that WFA induces autophagosomes-lysosomes fusion. WFA-induced autolysosomes exhibit intact protein degradation activity as evident with cathepsin-D activation and DQ-BSA assays. Importantly, we present that inhibiting WFA-induced autophagy either by blocking autophagosome-formation or by elevating lysosomal pH (Chloroquine and Bafilomycin) enhances WFA-induced growth-inhibition and apoptosis, indicating the presence of cytoprotective autophagy. Indeed, WFA and CQ combination shows synergism and higher efficacy in comparison to either monotherapy. Collectively, we reveal that the efficacy of WFA is somewhat diminished by the concomitant induction of cytoprotective autophagy which can be successfully conquered by cotreatment with CQ, and we pave the way for development of a novel combination therapeutic strategy for HCC.

Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations

Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to2016. We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change. Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans. We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

The Acute Blood Loss Anemia Mystery

Presentation and outcomes related to hepatocellular carcinoma (HCC) tumor rupture vary greatly. We present a unique case of spontaneous rupture of HCC. A 64 year-old male with history of HCV cirrhosis, ascites, portosystemic encephalopathy, esophageal varices, presented with worsening weakness, lethargy, and gait instability. On presentation, he was alert and oriented with dry mucous membranes, scleral icterus, a mildly distended non-tender abdomen, trace bilateral lower extremity edema, without asterixis. The patient was hemodynamically stable and labs showed hemoglobin (hb) 12.0 g/dL, platelet 47 k/uL, INR 1.6, and ammonia 148 umol/L. Treatment was initiated with fluids and lactulose for volume depletion and grade I hepatic encephalopathy (HE). An IR-guided diagnostic paracentesis was negative for SBP. Few days later, the patient developed hypotension with a drop in Hb to 6.5 g/dL without overt GI bleeding. After transfusion, an EGD showed portal hypertensive gastropathy, and three columns of non-bleeding grade II varices that were prophylactically banded. Five days later, patient again became hypotensive with worsening HE, hyperkalemia, elevated creatinine and severe anemia (hb 4.7 g/dL), still without overt evidence of GI bleeding. Urgent diagnostic ultrasound guided paracentesis was consistent with hemoperitoneum. Emergent CTA (Figures 2, 3) revealed a 3.1 x 3.7cm exophytic lesion in the right hepatic lobe, with high density within, suggesting spontaneous rupture of HCC with active extravasation and intra-peritoneal hemorrhage. IR obtained hemostasis with gelfoam embolization of the right hepatic branches. Transplant hepatology service deemed the patient not to be a candidate due to risk of HCC seeding from ruptured tumor. HCC related mortality is commonly due to tumor progression and liver failure. The overall risk of spontaneous HCC tumor rupture is relatively low (3-30%), but with very high mortality risk (20-70%). Risk factors for rupture include hypertension, cirrhosis, portal hypertension, portal vein thrombosis and tumor location, size, and degree of extra-hepatic protrusion. Improved survival rates can be seen after embolization and radical resection. The patient's history, presentation, and recurrent acute unexplained anemia with overt GI bleed put him at high risk of tumor rupture. This case highlights the progression of HCC leading to hemorrhagic shock from a ruptured exophytic lesion in the setting of decompensated cirrhosis.2291_B Figure 2. CTA, arterial phase, with arrow pointing to exophytic liver lesion now measuring 3.1 x 3.7 cm compared to prior CT. There is high density within it equaled to the density within the hepatic vessels suggesting spontaneous rupture of hepatocellular carcinoma with active extravasation.2291_C Figure 3. CTA, Portovenous phase, arrow points to liver lesion.2291_A Figure 1. CT imaging 2-months prior to presentation with cirrhotic and shrunken liver. Arrow points to stable 2.3 cm exophytic mass arising from the lateral right hepatic lobe. There are small hypodense foci throughout the liver, too small to access.

Identification of a co-target for enhancing efficacy of sorafenib in HCC through a quantitative modeling approach.

Sorafenib (SFB), a multi-kinase inhibitor, is the only approved drug for treating hepatocellular carcinoma (HCC). However, SFB shows low efficacy in many cases. HCC related mortality therefore remains to be high worldwide. SFB, a multi-kinase inhibitor is also known to modulate the redox homeostasis in cancer cells. To understand the effect of SFB on the redox status, a quantitative understanding of the system is necessary. Kinetic modeling of the relevant pathways is a useful approach for obtaining a quantitative understanding of the pathway dynamics and to rank the individual factors based on the extent of influence they wield on the pathway. Here, we report a comprehensive model of the glutathione reaction network (GSHnet ), consisting of four modules and includes SFB-induced redox stress. We compared GSHnet simulations for HCC of six different etiologies with healthy liver, and correctly identified the expected variations in cancer. Next, we studied alterations induced in the system upon SFB treatment and observed differential H2 O2 dynamics in all the conditions. Using metabolic control analysis, we identified glutathione S-transferase (GST) as the enzyme with the highest selective control coefficient, making it an attractive co-target for potentiating the action of SFB across all six etiologies. As a proof-of-concept, we selected ethacrynic acid (EA), a known inhibitor of GST, and verified exvivo that EA synergistically potentiates the cytotoxic effect of SFB. Being an FDA approved drug, EA is a promising candidate for repurposing as a combination therapy with SFB for HCC treatment.

Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

ObjectiveTo describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region.DesignObservational cohort study.SettingDeath certificate data from the...

Le dépistage du carcinome hépatocellulaire

Hepatocellular carcinoma related mortality is one of the highest among all cancers. Ninety percent of all hepatocellular carcinoma develop in the context of liver cirrhosis. Liver cirrhosis is not recognized prior to the diagnosis of hepatocellular carcinoma in 25% of the cases, despite the existence of risk factors. Hepatocellular carcinoma is diagnosed within a surveillance program in less than 25% of the cases. Ultrasound screening for hepatocellular carcinoma every 6months increases chances to diagnose HCC at an early stage amenable to curative treatment, and increases survival. Interval greater than 7months between ultrasound imaging has a significant negative impact on survival. All patients diagnosed with cirrhosis have to perform an ultrasound screening for hepatocellular carcinoma and comply with the six months rule.

The Number and Response to Locoregional Therapy as a Bridge to Transplant Improves Overall Survival in Hepatocellular Carcinoma Patients After Liver Transplantation: An Observational Study

Introduction: With continual organ shortage, liver transplant (LT) wait list (WL) times are prolonging. For Hepatocellular carcinoma (HCC), WL of over 6-12 months is a risk factor for tumor progression beyond Milan's criteria. Locoregional therapies (LRT) are used as bridge to LT and decrease dropout rates. The data on the number of LRTs, and the response to LRT as assessed by mRECIST with their impact on survival is scarce. We aim to study the impact of the number and radiologic response to LRT, on overall survival in WL patients who undergo LT. Methods: 77 consecutive patients with liver cirrhosis (Mean age 60 ± 6.5 years, M/F=61:16) from our prospectively compiled database listed for LT from January 2009 to August 2014 for HCC were included. Tumor response by mRECIST was classified as favorable response (FR) including complete necrosis or partial response and unfavorable response (UR) including stable disease or progression. Survival was estimated using Kaplan-Meyer analysis and p-value of < 0.05 was considered significant. Results: Of 77 enrolled patients 54 had atleast one LRT performed. Among 13 who did not recieve LRT but underwent LT; 4 had HCC diagnosed on explant and 9 were transplanted within 6 weeks of HCC diagnosis and their lab MELD was higher than patients who received LRT(p< 0.001). From the 54 patients who recieved LRT while on WL, 14 were delisted: 8 due to HCC progression and 6 due to multiple comorbidities. 40 patients who had atleast 1 LRT underwent LT, mRECIST data was not available on only 1 patient.The 5 year survival (Figure 1) among LT recipients who received > 2 LRTs and had FR was 100% (4/4) and who had unfavorable response was 86% (1/7 deaths). The 5 year survival in LT recipients who received 2 LRTs and had favorable response had the best post-LT survivals. The median OS of 77 patients listed for LT was 5.3 years. HCC related mortality in patients who had LRT before LT was 5% (2/40). This was lower than in non-LRT transplanted patients who showed HCC related mortality of 15.4% (2/13). This difference was not statistically significant.Figure 1Conclusion: In our patient cohort, more than 2 LRTs and a favorable response to LRT improved posttransplant survivals in LT recipients. Prospective randomized trials are warranted

National Antiviral Treatment Program and the Incidence of Hepatocellular Carcinoma and Associated Mortality in Taiwan

Taiwan's Bureau of National Health Insurance launched the National Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral drugs and interferons for chronic hepatitis B and C. The objective was to examine the impact of the NATP on the incidence and mortality due to hepatocellular carcinoma (HCC). The cumulative numbers of NATP participants were retrieved from the National Health Insurance claims database. The national incidence and mortality rates of HCC were obtained from the Taiwan Cancer Registry in each quarter from 1979 to 2009. An interrupted time-series analysis was applied to test the temporal trend change before and after NATP. From 1979 to 1995, the HCC incidence increased in men and women of all age groups. From 2003 to 2009, 31,155 men and 10,769 women received anti-hepatitis B virus therapy, whereas 13,939 men and 10,721 women received anti-hepatitis C virus therapy. The incidence of HCC reached a plateau and then started to decline in men aged 30-39 (slope change P=0.003), 50-59 (P=0.051), and 60-69 years (P<0.001). A similar trend was noted in women aged 50-59 (P=0.035), 60-69 (P=0.006), and 70-79 years (P=0.052). The HCC mortality rate had been decreasing since 1996 and a further decline was observed after 2004 in men aged 60-69 years and women aged 60-79 years. There is a strong temporal relationship between NATP and the stabilization of the HCC incidence and related mortality. The cost-effectiveness of the NATP needs further evaluation.

Abstract C29: Free fatty acid induced epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma cells

Abstract Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) have steadily increased in the United States over the past few decades. From an epidemiological perspective, it has been observed that HCC related mortality rates are significantly higher in obese patients indicating a possible correlation between obesity and metastatic progression of HCC. At the physiological level, obesity manifests an elevation in free fatty acid levels (FFA) levels which is thought to be detrimental for liver cells. While most previous studies have focused on cytotoxic effects of elevated FFA, very few studies have investigated their potential role in progression of liver cancer. In a previous study, we found reduced expression of desmoplakin (DSP) in FFA treated HepG2 cells, suggesting a loss of cell adhesion – one of the features of cells undergoing metastatic progression via EMT. Hence, we hypothesized that elevated FFA levels possess the ability to induce EMT in HCC cells. Methodology and Results: We studied the in vitro effects of FFA on HepG2 and Hep3B cells – two human HCC cell lines of different etiologies. We performed all experiments using FFA conjugated to BSA (bovine serum albumin), and used BSA as treatment control. We first evaluated the overall impact of FFA treatment on cell adhesion. We performed a dispase-based dissociation assay and found significant loss of cell adhesion in FFA treated cells. Next, using scratch wound-healing assay and modified Boyden's chamber assay, we found that FFA significantly enhanced the migration and invasiveness of HCC cells. We further confirmed the occurrence of EMT by measuring the change in expression levels of various markers (Keratin 8/18, Vimentin, E-cadherin) in FFA treated cells using Western blots. Additionally, we screened the change in expression levels of several transcription factors that have been described as inducers of EMT using qRT-PCR. Our studies indicated enhanced expression of a number of EMT-related transcription factors including SNAIL, TWIST, ZEB1 and FOXC2, suggesting a potential transcriptional regulatory mechanism by which elevated FFA could induce EMT. Furthermore, we evaluated the possibility of a direct role of DSP loss in inducing EMT. Using siRNA mediated DSP knock-down we found enhanced expression of EMT markers in both HepG2 and Hep3B cells. Conclusions and future perspectives: Our studies provide evidence that elevated FFA levels may be involved in metastatic progression of HCC cells through transcriptional activation of EMT pathways. Future in vivo studies based on mouse xenograft model will provide additional support to confirm the effects of elevated FFA and DSP loss on enhancing aggressiveness and metastatic potential of HCC. These results may impact HCC therapeutic intervention and drug development, as well as future studies on obesity as a risk factor for cancer tumorigenesis and progression. Citation Format: Aritro Nath, Christina Chan. Free fatty acid induced epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C29.

Comparative analysis of treatments, utilization, and survival benefit in HCC patients: A real-world analysis of SEER Medicare.

214 Background: We explore various treatments at all stages of Hepatocellular Carcinoma (HCC), in a SEER (Surveillance, Epidemiology and End-Results Program) Medicare population and assess their impact on HCC-specific and overall survival. Methods: Medicare enrollees, older than 65, with an initial diagnosis of a primary HCC between 2000-07 were followed up through end of 2009. Data are from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Using multivariate Cox-proportional hazards models, we assessed overall and HCC-related mortality in relation to receipt of treatment/no treatment, adjusting for demographics, general health status (CCI), cancer stage and liver conditions. Results: Out of the 9054 HCC patients, older than 65, who did not get a liver transplant, 76% were Caucasian, 8% African American (AA), 63% male, and 37% got treatment [12% transarterial chemoembolization (TACE), 12% systemic chemotherapy, 1.5% selective internal radiation therapy (SIRT), 9% external beam radiation therapy (EBRT), 8% surgical resection and 9% ablative therapy]. Treatment was associated with a reduction of overall (HR=0.35, P= &lt;0.001) and HCC-related (0.33, &lt;0.001) mortality. HCC-related mortality was significantly reduced in those getting resection (0.38, &lt;0.001), ablation (0.59, &lt;0.001), TACE (0.76, &lt;0.001), EBRT (0.85, 0.017), or chemotherapy (0.85, 0.013). Significant reduction in overall mortality was seen with resection, ablation and TACE but not with chemotherapy, EBRT or SIRT. No particular treatment was associated with greater mortality reduction in early vs advanced stages. Patients with poor underlying health status (CCI&gt;1) had higher mortality (1.27, &lt;0.001). Alcohol related disease, Hep C, and moderate/severe liver dysfunction were not significantly associated with overall or HCC related mortality. Caucasians and non-African Americans had lower overall mortality (0.87, &lt;0.001). Conclusions: In HCC SEER Medicare patients, all treatments except SIRT were associated with a significant reduction in HCC related mortality. A limitation of this study is that, through the data, we cannot accurately depict the severity of the disease.

Population-based study of hepatitis C virus infection and hepatocellular carcinoma in western Japan

Hepatitis C virus (HCV) infection is a major health problem in Japan. This infection is highly prevalent in subjects with chronic liver disease and is strongly associated with hepatocellular carcinoma. Epidemiological studies conducted by the Japanese Ministry of Health and Welfare showed that the mortality rate associated with hepatocellular carcinoma (HCC) was high in several prefectures in western Japan. In 1990, Saga Prefecture on the island of Kyushu in western Japan reported the highest HCC related mortality rate. Here, we report the results of a population-based survey in Saga Prefecture, where prevalence of HCV infection and mortality rate of HCC was assessed in the general population. From 1992 to 1997, the prevalence of HCV infection was assessed in the general population of 47 districts in Saga Prefecture. Among the 161 307 subjects (52 590 men, 108 357 women, older than 30 years) examined, 13 129 (8.1%) reacted positively to HCV antibody (anti-HCV). The prevalence of HCV-Ab reactivity was highest in subjects over 60 years of age. Reactivity increased from 3.6% in subjects 30–49 years old to 11% in those >50 years old. Highly significant differences were observed among the 45 districts in seropositive rates for anti-HCV, with the range being from 0.8 to 20.0%. We evaluated the association between the prevalence of anti-HCV reactivity and age-adjusted death rate from HCC in the general population of these districts, and detected a significant association (Pearson’ s correlation coefficient=0.721, P<0.0001, Y=1.86 X+16.1). In conclusion, these observations indicated that the outbreak of HCV in this area was a major cause of HCC in the population.