The effect of chronic viral hepatitis on prognostic value of inflammatory biomarkers in hepatocellular carcinoma.

BACKGROUND: Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. METHODS: Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan-Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). RESULTS: A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low-NLR group (

Direct-Acting Antivirals Improve Overall Survival in Interventional Oncology Patients with Hepatitis C and Hepatocellular Carcinoma.

PURPOSE: To investigate the impact of direct-acting antivirals (DAAs) and 12-week sustained virologic response (SVR12) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) treated by interventional oncology (IO) therapies. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed from 2005 to 2016 with HCC and receiving IO therapies. A total of 478 patients met inclusion criteria. Patients were age 29-90 years (mean 63.6 ± 9.4 years) and 78.9% (n =3 77) male. Two hundred and eighty-five (57%) patients had chronic HCV, 93 (33%) received DAAs, and 63 (68%) achieved SVR12. Liver function, tumor characteristics, and IO therapy including ablation, image-guided transcatheter tumor therapies (ITTT) (eg, chemoembolization and radioembolization), and combination locoregional therapy were assessed in analysis. RESULTS: Median overall survival (OS) of the cohort was 26.7 months (95% confidence interval [CI] 21.9-29.9). OS for ablation, combination locoregional therapy and ITTT, was 37.3 (CI 30.7-49.9), 29.3 (CI 24.2-38.0), and 19.7 months (CI 16.5-22.8), respectively (P < .0001). OS in patients with HCV was 30.7 months (CI 24.2-35.2) versus 22.2 months in non-HCV patients (CI 17.8-27.8, P = .03). Patients with HCV who received DAA had higher survival, 49.2 months (CI 36.5-not reached) versus those not receiving DAA, 18.5 months (CI 14.1-25.3, P < .0001). OS was 71.8 months (CI 42.3-not reached) for patients who achieved SVR12 after DAA versus 26.7 months in the non-SVR12 group (CI 15.9-31.1, P < .0001). Multivariable analysis revealed independent factors for OS including IO treatment type, DAA use and achieving SVR12 (P < .05). CONCLUSIONS: DAA use and SVR12 is associated with higher OS in patients with HCV-related HCC treated by IO therapies.

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma.

With the increasing use of direct-acting antivirals (DAA) for treatment of chronic hepatitis C virus (HCV) infection, we looked at the impact of DAA use and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and HCV. This is a retrospective analysis of 969 HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Median overall survival of the cohort was 24.2 months. 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (67.4%). HCV-positive and HCV-negative patients had similar survival, 20.7 months vs 17.4 months (p = 0.22). Patients receiving DAA therapy had an overall survival of 71.8 months vs 11.6 months for patients without (p < 0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months vs. 26.7 months in the non SVR12 group (p < 0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location, cancer treatment type, receiving DAA treatment and achieving SVR12 had independent influence on survival (p < 0.05). This suggests DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.

Hepatocellular carcinoma: Impact of academic setting and hospital volume on patient survival.

BACKGROUND AND OBJECTIVES: To assess the impact of academic setting and hospital on overall survival in patient with hepatocellular carcinoma (HCC). METHODS: The 2004-2015 NCDB was queried for HCC. First line treatment was stratified as liver transplant, surgical resection, interventional oncology (IO) and chemotherapy. Hospital volume was stratified as high (ranking among top 10% in case numbers) and low volume. Overall survival was assessed via multivariable Cox regressions. RESULTS: 63,877 patients treated at 1261 hospital systems were included (transplant n = 10,596, surgical resection n = 11,132, IO n = 12,286, chemotherapy n = 29,863; academic centers n = 226, non-academic n = 1035). Younger African American patients with private insurance, high income and education were more likely treated at academic centers. US geographical discrepancies were evident, with highest academic center treatment rates in New England states (83.6%) and lowest in South Atlantic states (48.6%). Overall survival was superior for academic versus non-academic centers (HR = 0.89, 95% CI: 0.87-0.91, p < 0.001) and high versus low volume centers (HR = 0.79, 95% CI: 0.77-0.81, p < 0.001), after multivariable adjustment for potential confounders. These effects were evident among all HCC treatment modalities. CONCLUSIONS: HCC treatment in academic centers shows distinct patterns according to patient demographics and US geography. Longest patient survival is observed in high-volume academic centers.

Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease.

BACKGROUND: To investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. METHODS: In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan-Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). RESULTS: About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child-Pugh A patients (P < 0.01). In Child-Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child-Pugh class A (n = 94), low-NLR had higher OS vs high-NLR (25.4 vs 12.2 months, P < 0.01). In Child-Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low- vs high-NLR: 6.7 vs 2.9 months, P = 0.2). Child-Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124). CONCLUSIONS: The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.

The impact of socioeconomic status on outcomes in hepatocellular carcinoma: Inferences from primary insurance.

BACKGROUND: To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan-Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses. RESULTS: Seven hundred and sixty-nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child-Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P < 0.0001) and higher MELD scores (median 11.0) vs Medicare (9.0) and private insurance (9.0, P = 0.0266). Across insurance groups, patients had similar distribution of American Joint Committee on Cancer stage, tumor size, and multifocal tumor burden. Patients with private insurance had the highest survival (median OS 21.9 months) vs Medicare (17.7 months) and Medicaid (13.0 months, overall P = 0.0061). On univariate analysis, Medicaid patients demonstrated decreased survival vs private insurance (HR 1.40, 95% CI: 1.146-1.715, P = 0.0011). After adjustment for liver disease factors, this survival difference lost statistical significance (Medicaid vs private insurance, HR 1.02, 95% CI: 0.819-1.266, P = 0.8596). CONCLUSION: Medicaid was associated with advanced liver disease at HCC diagnosis; however, insurance status is not an independent predictor of HCC survival.

Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database.

OBJECTIVE: The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC). METHODS: The 2004-2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models. RESULTS: Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16-1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01-1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04-1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65-0.82, p < 0.001). CONCLUSIONS: ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.

Transjugular intrahepatic portosystemic shunt as a bridge to liver transplant: Current state and future directions.

Liver transplantation is one of the mainstays of treatment for liver failure due to severe chronic liver disease. Bridging therapies, such as placement of a transjugular intrahepatic portosystemic shunt (TIPS), are frequently employed to control complications of portal hypertension such as ascites, hydrothorax, and variceal bleeding, and thereby reduce morbidity in patients awaiting transplant. There is no significant difference seen in either graft survival or patient survival between those receiving TIPS pre-transplant and those who do not, although those receiving TIPS placement on average have a longer waiting time on the transplant waitlist. Locoregional therapies, such as thermal ablation or chemoembolization, can be efficacious in patients with HCC and pre-existing TIPS; however there is a risk for increased adverse events in patients receiving these therapies who have TIPS compared to those who do not. In summary, TIPS is a safe, effective treatment that can be used to ameliorate the complications that are sequelae of portal hypertension. While it does not appear to improve survival post-transplant, TIPS placement pre-transplant may increase survival time to transplant, thus improving overall survival as well as quality of life.

Radiofrequency ablation versus surgical resection of hepatocellular carcinoma: contemporary treatment trends and outcomes from the United States National Cancer Database.

PURPOSE: To compare utilization and effectiveness of radiofrequency ablation (RFA) and surgical resection for hepatocellular carcinoma (HCC). METHODS: The 2004-2015 United States National Cancer Database was queried for HCC patients treated by RFA and surgical resection. Patients were 1:1 propensity score matched. Duration of hospital stay, unplanned readmission rates, and overall survival (OS) were compared in the matched cohort via multivariable regression models. RESULTS: Eighteen thousand two hundred ninety-six patients were included (RFA, n = 8211; surgical resection, n = 10,085). RFA was more likely in young male whites with high degree of hepatic fibrosis, high bilirubin levels, high INR, and multifocal HCC; resection was more likely in those with private insurance, high income, high cancer grade and stage, and larger HCC. RFA rates varied between 32.3% (East South Central) and 58.5% (New England). Post-treatment outcomes were superior for RFA versus resection regarding duration of hospital stay (median 1 vs. 5d, p < 0.001), 30-day unplanned hospital readmission rates (3.1% vs. 4.5%, p < 0.001), and 30-/90-day mortality (0% vs. 4.6%/8%, p < 0.001). Overall survival was comparable for RFA and resection for severe hepatic fibrosis/cirrhosis (5-year OS 37.3% vs. 39.4%, p = 0.07), for patients > 65 years old (5-year OS 21.9% vs. 26.5%, p = 0.47), and for HCC < 15 mm (5-year OS 49.7% vs. 52.3%, p = 0.78). OS in the full cohort was superior for surgical resection (5-year OS 29.9% vs. 45.7%, p < 0.01). CONCLUSION: RFA for HCC shows substantial variation by geography, socioeconomic factors, liver function, and tumor extent. RFA offers superior post-treatment outcomes versus surgical resection and may be an alternative for older patients with cirrhosis and/or small HCC. KEY POINTS: • Duration of hospital stay, unplanned readmissions, and 30-/90-day mortality are lower for RFA versus surgical resection. • RFA and surgical resection show similar survival in severe hepatic fibrosis. • In HCC < 15 mm, RFA and surgical resection yield similar survival.