Mortality In Hepatocellular Carcinoma Patients Research Articles

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review.

Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Analysis of competing risks of cardiovascular death in patients with hepatocellular carcinoma: A population-based study.

Clinical data has shown that cardiovascular diseases (CVDs) have emerged as a prominent cause of mortality in individuals with hepatocellular carcinoma (HCC). This research aimed to reveal the comorbid effects of CVDs in patients with HCC. The cardiovascular mortality of patients diagnosed with HCC between 2000 and 2014 was compared to that of the general US population. Standardized mortality ratios were calculated to quantify the relative risk of cardiovascular mortality in HCC patients. The cumulative incidence of cardiovascular death (CVD) was estimated using Fine-Gray testing, and independent risk factors for CVD were determined using competing risk models. The results were analyzed using the Kaplan-Meier analysis. The overall SMR for CVD in HCC patients was 11.15 (95% CI: 10.99-11.32). The risk of CVD was significantly higher in patients aged < 55 years (SMR: 56.19 [95% CI: 54.97-57.44]) compared to those aged ≥ 75 years (SMR: 1.86 [95% CI: 1.75-1.97]). This study suggests that patients with HCC are at significant risk of developing CVD. Competing risk analyses indicated that age, grade, tumor size, surveillance, epidemiology, and end results stage, and surgical status were independent risk factors for CVD in patients with HCC. Therefore, patients with HCC require enhanced preventive screening and management of CVDs during and after treatment to improve patient survival.

Combining a deep learning model with clinical data better predicts hepatocellular carcinoma behavior following surgery

Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently.

Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma

Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effects, including malignancy. The effects of tacrolimus IPV in liver transplant recipients with and without hepatocellular carcinoma (HCC) are unknown. We investigated the association between tacrolimus IPV and transplant outcomes in 636 liver transplant patients. Tacrolimus IPV was determined by calculating the coefficient of variance (CV) of outpatient tacrolimus trough levels from 3 to 12 months after transplantation. High tacrolimus IPV was defined as CV > 30%. Patients were grouped according to tacrolimus IPV and HCC status. Among 636 liver transplant patients, 349 had HCC and 287 had no HCC. Overall survival in HCC patients was significantly reduced with high tacrolimus IPV (P < 0.001), whereas survival of non-HCC patients was not associated with tacrolimus IPV. Multivariable analysis confirmed the independent association between high tacrolimus IPV and overall mortality in HCC patients (HR, 3.010; 95% CI, 1.084–4.918). HCC recurred in 59 patients (16.9%) post-transplantation. After adjusting for donor/recipient factors, immunosuppression, and tumor characteristics, high tacrolimus IPV was independently associated with an increased risk of HCC recurrence (HR, 2.196; 95% CI, 1.272–3.791). High tacrolimus IPV was associated with significantly increased risks of overall mortality and HCC recurrence in liver transplant recipients with HCC.

Liver transplantation with simultaneous splenectomy increases risk of cancer development and mortality in hepatocellular carcinoma patients.

BACKGROUNDSplenectomy has previously been found to increase the risk of cancer development, including lung, non-melanoma skin cancer, leukemia, lymphoma, Hodgkin’s lymphoma, and ovarian cancer. The risk of cancer development in liver transplantation (LT) with simultaneous splenectomy remains unclear. AIMTo compare hepatocellular carcinoma (HCC) recurrence and de novo malignancy between patients undergoing LT with and without simultaneous splenectomy.METHODSWe retrospectively analyzed the outcomes of 120 patients with HCC within the University of California San Francisco criteria who received LT with (n = 35) and without (n = 85) simultaneous splenectomy in the Tri-Service General Hospital. Univariate and multivariate Cox regression analyses for cancer-free survival and mortality were established. The comparison of the group survival status and group cancer-free status was done by generating Kaplan–Meier survival curves and log-rank tests. RESULTSThe splenectomy group had more hepatitis C virus infection, lower platelet count, higher -fetoprotein level, and longer operating time. Splenectomy and age were both positive independent factors for prediction of cancer development [hazard ratio (HR): 2.560 and 1.057, respectively, P < 0.05]. Splenectomy and hypertension were positive independent factors for prediction of mortality. (HR: 2.791 and 2.813 respectively, P < 0.05). The splenectomy group had a significantly worse cancer-free survival (CFS) and overall survival (OS) curve compared to the non-splenectomy group (5-year CFS rates: 53.4% vs 76.5%, P = 0.003; 5-year OS rate: 68.1 vs 89.3, P = 0.002). CONCLUSIONOur study suggests that simultaneous splenectomy should be avoided as much as possible in HCC patients who have undergone LT.

Machine learning models in the prediction of 1-year mortality in patients with advanced hepatocellular cancer on immunotherapy: a proof-of-concept study.

Immunotherapy is a new promising treatment for patients with advanced hepatocellular carcinoma (HCC), but is costly and potentially associated with considerable side effects. This study aimed to evaluate the role of machine learning (ML) models in predicting the 1-year cancer-related mortality in advanced HCC patients treated with immunotherapy. 395 HCC patients who had received immunotherapy (including nivolumab, pembrolizumab or ipilimumab) between 2014 and 2019 in Hong Kong were included. The whole data sets were randomly divided into training (n = 316) and internal validation (n = 79) set. The data set, including 47 clinical variables, was used to construct six different ML models in predicting the risk of 1-year mortality. The performances of ML models were measured by the area under receiver operating characteristic curve (AUC) and their performances were compared with C-Reactive protein and Alpha Fetoprotein in ImmunoTherapY score (CRAFITY) and albumin-bilirubin (ALBI) score. The ML models were further validated with an external cohort between 2020 and 2021. The 1-year cancer-related mortality was 51.1%. Of the six ML models, the random forest (RF) has the highest AUC of 0.92 (95% CI 0.87-0.98), which was better than logistic regression (0.82, p = 0.01) as well as the CRAFITY (0.68, p < 0.01) and ALBI score (0.84, p = 0.04). RF had the lowest false positive (2.0%) and false negative rate (5.2%), and performed better than CRAFITY score in the external validation cohort (0.91 vs 0.66, p < 0.01). High baseline AFP, bilirubin and alkaline phosphatase were three common risk factors identified by all ML models. ML models could predict 1-year cancer-related mortality in HCC patients treated with immunotherapy, which may help to select patients who would benefit from this treatment.

The Impact of Socioeconomic Status on Mortality in Patients with Hepatocellular Carcinoma: A Korean National Cohort Study.

We studied the impact of socioeconomic status (SES) on mortality in hepatocellular carcinoma patients and analyzed the effect of SES on initial treatment allocation. A cohort study was conducted using data from the National Health Insurance Service- National Sample Cohort of Korea. A total of 3,032 hepatocellular carcinoma patients who were newly diagnosed between January 2003 and December 2013 were included. Income level was categorized as Medical Aid and ≤30th, 31st-70th, or >70th percentile as an SES indicator. The proportion of Medical Aid was 4.3%. The highest risks of all-cause mortality associated with Medical Aid were evident in the transcatheter arterial chemoembolization group (fully adjusted hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.25 to 4.58), the other treatments group (fully adjusted HR, 2.86; 95% CI, 1.85 to 4.41), and the no treatment group (fully adjusted HR, 2.69; 95% CI, 1.79 to 4.04) but not in the curative treatment group. An association between the lower-income percentile and higher liver cancer-specific mortality was also observed, except in the curative treatment group. The association between income percentile and all-cause mortality was nonlinear, with a stronger association in the lower-income percentiles than in the higher income percentiles (p-value for nonlinear spline terms <0.05). Patients in the lower SES group, especially patients not eligible for curative treatment, had an increased risk of mortality. In addition, the association between SES and the risk for mortality was stronger in the lower-income percentile than in the moderate to higher income percentiles.

Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma

BackgroundHepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade.MethodsWe derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors.ResultsA total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities.ConclusionsIn this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.

Antiviral Therapy Reduces Mortality in Hepatocellular Carcinoma Patients with Low-Level Hepatitis B Viremia.

Background and AimsAlthough antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels.MethodsA retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan–Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC.ResultsAfter propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530–0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia.ConclusionAntiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.

Does low income effects 5-year mortality of hepatocellular carcinoma patients?

BackgroundIn Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality.MethodsThe Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated with the survival probability of HCC patients.ResultsFrom 2004 to 2008, there were 4658 new HCC cases among males and 2667 new cases among females. The 5-year survival proportion of males was 68%, and the incidence per person-year was 0.768; the female survival proportion was 78%, and the incidence per person-year was 0.819. Lower income was associated with higher hazard ratio (HR), and HCC patients with hepatitis B (HBV), alcoholic liver cirrhosis, and other types of liver cirrhosis had higher HRs than those without these conditions. Subgroup analyses showed that middle-aged men were most vulnerable to the effects of low income on 5-year mortality, and community-level characteristics were associated with survival of HCC patients.ConclusionHaving a low income significantly affected the overall 5-year mortality of Korean adults who were newly diagnosed with HCC from 2004 to 2008. Middle-aged men were the most vulnerable. We believe our findings will be useful to healthcare policymakers in Korea as well as to healthcare leaders in countries with NHI programs who need to make important decisions about allocation of limited healthcare resources according to a consensually accepted and rational framework.

Increased morbidity and mortality of hepatocellular carcinoma patients in lower cost of living areas.

BACKGROUNDThe incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in the United States. However, the increases in different racial and socioeconomic groups have not been homogeneous. Access to healthcare based on socioeconomic status and cost of living index (COLI), especially in HCC management, is under characterized.AIMThe aim was to investigate the relationship between the COLI and tumor characteristics, treatment modalities, and survival of HCC patients in the United States.METHODSA retrospective study of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HCC between 2007 and 2015 using site code C22.0 and the International Classification of Disease for Oncology, 3rd edition (ICD-O-3) codes 8170-8173, and 8175. Cases of fibrolamellar HCC were excluded. Variables collected included demographics, COLI, insurance status, marital status, stage, treatment, tumor size, and survival data. Interquartile ranges for COLI were obtained. Based on the COLI, the study population was separated into four groups: COLI ≤ 901, 902-1044, 1045-1169, ≥ 1070. The χ2 test was used to compare categorical variables, and the Kruskal-Wallis test was used to compare continuous variables without normal distributions. Survival was estimated by the Kaplan-Meier method. We defined P < 0.05 as statistically significant.RESULTSWe identified 47,894 patients with HCC. Patients from the highest COLI areas were older (63 vs 61 years of age), more likely to be married (52.8% vs 48.0%), female (23.7% vs 21.1%), and of Asian and Pacific Islander descent (32.7% vs 4.8%). The patients were more likely to have stage I disease (34.2% vs 32.6%), tumor size ≤ 30 mm (27.1% vs 23.1%), received locoregional therapy (11.5% vs 6.1%), and undergone surgical resection (10.7% vs 7.0%) when compared with the lowest quartile. The majority of patients with higher COLIs resided in California, Connecticut, Hawaii, and New Jersey. Patients with lower COLIs were more likely to be uninsured (5.7% vs 3.4%), have stage IV disease (15.2% vs 13%), and have received a liver transplant (6.6% vs 4.4%) compared with patients from with the highest COLI. Median survival increased with COLI from 8 (95%CI: 7-8), to 10 (10-11), 11 (11-12), and 14 (14-15) mo (P < 0.001) among patients with COLIs of ≤ 901, 902-1044, 1045-1169, ≥ 1070, respectively. After stratifying by year, a survival trend was present: 2007-2009, 2010-2012, and 2013-2015.CONCLUSIONOur study suggested that there were racial and socioeconomic disparities in HCC. Patients from lower COLI groups presented with more advanced disease, and increasing COLI was associated with improved median survival. Future studies should examine this further and explore ways to mitigate the differences.

MRI-Derived Sarcopenia Associated with Increased Mortality Following Yttrium-90 Radioembolization of Hepatocellular Carcinoma.

To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated with 90Y radioembolization. This single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65years, range 31-83years) with HCC treated with 90Y radioembolization between December 2013 and December 2017. Sarcopenia was assessed on pre-procedure MRI performed within 100days prior to 90Y radioembolization by segmenting the paraspinal musculature at the level of the superior mesenteric artery origin and subtracting fat-intensity pixels to yield fat-free muscle area (FFMA). Sarcopenia was defined as FFMA ≤31.97 cm2 for men and ≤28.95 cm2 for women. Survival at 90days, 180days, 1year, and 3years following initial treatment was assessed using medical and public obituary records. Sarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6months, range 21days-58months). Patients with sarcopenia were found to have increased mortality at 180days (31.8% vs. 8.9%) and 1year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease. Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing 90Y radioembolization. Sarcopenia was an independent predictor of survival adjusted for BCLC stage with significant deviation in the survival curves of BCLC stage B patients with and without sarcopenia.

Effect of oral administration of branched-chain amino acids supplementation on the mortality of patients with hepatocellular carcinoma: a meta-analysis

Objective: To investigate the effect of oral administration of branched-chain amino acids (BCAA) supplementation on the mortality of patients with hepatocellular carcinoma (HCC) after treatment. Methods: Computer searching of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database was conducted to search for clinical controlled trials and randomized controlled trials (RCTs) on the effect of oral administration of BCAA on the mortality of patients with HCC. The retrieval time limit was from the time of the establishment of each database to December 30, 2019. Two researchers independently screened the literature and extracted the data. Another researcher assessed the risk of bias in the included studies and then used RevMan 5.3 software for meta-analysis. Results: A total of 14 studies were included with 1 179 patients. The overall results showed that oral administration of BCAA had no significant effect on the mortality of HCC patients at 1 year after treatment (RR=0.85, 95%CI:0.68-1.06, P=0.16), while the mortalities of patients at 3 years (RR=0.73, 95%CI: 0.61-0.88, P=0.000 7) and 5 years (RR=0.57, 95%CI:0.34-0.96, P=0.03) after treatment were significantly lower than those of the control group. The subgroup analysis showed that for radiofrequency ablation (RFA) patients, there was no significant difference in 1-year mortality between the BCAA group and the control group (RR=0.96, 95%CI:0.14-6.5, P=0.97), while 3-year mortality was significantly reduced (RR=0.59, 95%CI:0.43-0.81, P=0.001); for hepatectomy patients, there was no significant differences in 1 -and 3-year mortality between the two groups (RR=0.90, 95%CI:0.44-1.88, P=0.79; RR=0.97, 95%CI:0.71-1.33, P=0.85, respectively). In addition, as for albumin levels, BCAA supplementation significantly increased albumin levels without considering the treatment of HCC (SD=0.45, 95%CI: 0.29-0.90; P=0.000 1), but had no significant effect on hepatectomy patients (SD=0, 95%CI: -0.41-0.41, P=0.99). Conclusion: BCAA supplementation might improve liver reserve function and long-term prognosis of HCC patients, which was related to the surgical method. Supplementing BCAA reduced the long-term mortality of RFA patients, but had no significant effect on hepatectomy patients.

Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

Objective:hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. Methods:we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. Results:patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p<0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). Conclusion:Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.

Sarcopenia is associated with lack of therapeutic response and higher mortality in hepatocellular carcinoma patients

Sarcopenia is associated with lack of therapeutic response and higher mortality in hepatocellular carcinoma patients

Demographic trends and in-hospital mortality data in patients with hepatocellular carcinoma.

e16648 Background: Hepatocellular carcinoma (HCC) remains the 4th leading cause of cancer related mortality in the US. The incidence of HCC in the US appears to be increasing in specific demographic subgroups (Caucasian males, Hispanics and in the Southern US). Older studies identified substantial racial and ethnic differences in treatment and survival in HCC. There is a lack of large scale studies exploring the mortality patterns in patients hospitalized with HCC. Methods: The National Inpatient Sample was used to extract admissions for HCC using the ICD-9 code 155.0 from the years 2010 to 2014. The sample was weighted to approximate the full inpatient population of the U.S. over the 5-year interval. Univariate analysis was performed to determine the frequency distribution and bivariate analysis was performed using Chi Square test to determine the in-hospital mortality percentage. Results: A total of 52,868 (weighted = 262845) admissions were extracted from the years 2010 to 2014. While the number of patients admitted with HCC steadily increased over the 5-year study period, the overall in-hospital mortality decreased significantly from 9.35% to 7.68% (p &lt; 0.0001). The mortality was highest for patients with African American ethnicity at 11.2% and for uninsured patients at 13%. The mortality rate among patients in the low income group (0-25th percentile) was 10.2 %, significantly higher (p = 0.0005) than other income groups. Conclusions: Even though the incidence of in-hospital mortality in HCC patients is decreasing, there appears to be a disparity in mortality data among patients of low socioeconomic status, self-pay or uninsured status and among African Americans. Our study further confirms the persistence of racial,economic and social disparities and highlights the need for additional equity research to understand the reasons for these differences and to improve outcomes for these subgroups of patients.

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis.

Background: Association between statin use and prognosis in patients with hepatocellular carcinoma (HCC) remains unknown. We performed a meta-analysis of follow-up studies to systematically evaluate the influence of statin use on clinical outcome in HCC patients.Methods: Studies were obtained via systematic search of PubMed, Cochrane’s Library, and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influence of study characteristics on the association.Results: Nine retrospective cohort studies were included. Overall, statin use was associated with a reduced all-cause mortality in HCC patients (risk ratio [RR]: 0.81, 95% CI: 0.74–0.88, P < 0.001; I2 = 63%). Subgroup analyses showed similar results for patients with stage I-III HCC (RR: 0.83, 0.79, and 0.90 respectively, P all < 0.01) and patients after palliative therapy for HCC (RR: 0.80, P < 0.001), but not for patents with stage IV HCC (RR: 0.91, P = 0.28) or those after curative therapy (RR: 0.92, P = 0.20). However, the different between subgroups were not significant (both P > 0.05). Moreover, statin use was associated with reduced HCC-related mortality (RR: 0.78, P = 0.001) in overall patient population and HCC recurrence in patients after curative therapies (RR: 0.55, P < 0.001).Conclusions: Satin use is associated with reduced mortality and recurrence of HCC. These results should be validated in prospective cohort studies and randomized controlled trials.

Thirty-Day Unplanned Readmission and Its Effect on 90-Day Mortality in Hepatocellular Carcinoma Patients Undergoing Partial Hepatectomy

Background : Despite advances of surgical techniques, hepatectomy continues to be potentially dangerous and is associated with postoperative mortality, morbidity and readmission. The objective of this study was to determine the effect of 30-day unplanned readmission on ‘conditional’ 90-day mortality among hepatocellular carcinoma (HCC) patients that underwent partial hepatectomy. Methods : National Cancer Database (NCDB) was queried from 2004 to 2012 for patients with hepatocellular carcinoma (HCC) who underwent partial hepatectomy. Thirty-day unplanned readmission rate, and associated risk factors, was determined for 7,696 patients. The association between 30-day unplanned readmission and conditional 90-day mortality was further addressed. Results : The 30-day unplanned readmission rate for patients with HCC that underwent partial hepatectomy was 5.2%. Risk factors associated with 30-day unplanned readmission were sex, race/ethnicity, Charlson-Deyo score, and annual hospital hepatectomy volume. An overall adjusted odds ratio of having conditional 90-day mortality was 2.325 times higher (95% CI 1.643 - 3.219) among patients with a history of 30-day unplanned readmission than those without. This association was dependent on age, sex, race/ethnicity, insurance status, alpha-fetoprotein (AFP), liver fibrosis, Charlson-Deyo comorbidity score and annual hospital hepatectomy volume. Conclusion : Efforts in patient care should be taken to reduce 30-day unplanned readmission after partial hepatectomy for patients with HCC to reduce conditional 90-day mortality.

Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model.

Background:Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy.Methods:In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse.Results:Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response.Conclusion:Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.

High interleukin-8 and/or extracellular signal-regulated kinase 2 expression predicts poor prognosis in patients with hepatocellular carcinoma.

Interleukin (IL)-8 and extracellular signal-regulated kinase (ERK) 2 play key roles in tumor progression, but the relationship between IL-8 and/or ERK2 expression in hepatocellular carcinoma (HCC) tissues and postoperative recurrence or survival is unclear. The expression levels of IL-8 and ERK2 in both HCC tissues and non-tumor liver tissues were analyzed using the Oncomine™ database and immunohistochemistry assay. Reverse transcription-quantitative PCR was then used to evaluate the expression levels of IL-8 and ERK2 in the tumor tissues of 67 patients with HCC undergoing radical hepatectomy. Pearson's correlation, Kaplan-Meier, Cox univariate and multivariate survival analyses were utilized to determine the correlation between IL-8 and ERK2 expression in HCC tissues, and their potential prognostic significance. As indicated by the data from the Oncomine™ database, and the patient samples, IL-8 and ERK2 were expressed at significantly higher levels in HCC tissues than in non-tumor liver tissues (P<0.05). The rates of high IL-8 and ERK2 expression in HCC tissues were 43.28 (29/67) and 34.33% (23/67), respectively, and the IL-8 and ERK2 expression levels were positively correlated (r=0.764; P<0.001). Both ERK2 expression and IL-8/ERK2 co-expression were significantly associated with tumor size and differentiation (P<0.05). Additionally, high expression levels of IL-8, ERK2 and IL-8/ERK2 co-expression were all significantly associated with poor overall survival (OS; P<0.05) and disease-free survival (DFS; P<0.05). Multivariate Cox regression analysis also showed that high expression levels of IL-8, ERK2, and IL-8 and ERK2 were independent prognostic factors for OS and DFS (P<0.05). The results of the present study indicate a significant increase in the risk of recurrence and mortality in HCC patients with high expression levels of IL-8 and/or ERK2, compared with patients with low expression. Therefore, IL-8 and ERK2 may be predictors of postoperative prognosis in patients with HCC.