Combined CRAFITY score and α-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving anti-programmed death-1 blockade-based immunotherapy.

Biomarkers for predicting the treatment efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with unresectable hepatocellular carcinoma (uHCC) are crucial. Previous studies demonstrated that C-reactive protein and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score at baseline predicted treatment outcomes and that patients with uHCC with AFP response, defined as > 15% decline in AFP level within the initial 3 months of ICI-based therapy, had favorable outcomes when receiving ICI-based therapy. However, whether the combination of CRAFITY score and AFP response could be used to predict treatment efficacy of programmed death-1 (PD-1) blockade-based therapy in uHCC patients remains unclear. We retrospectively enrolled 110 consecutive uHCC patients from May 2017 to March 2022. The median ICI treatment duration was 2.85 (1.67-6.63) months, and 87 patients received combination therapies. The objective response and disease control rates were 21.8% and 46.4%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 2.87 (2.16-3.58) months and 8.20 (4.23-12.17) months, respectively. We categorized patients into three groups based on CRAFITY score (2 vs 0/1) and AFP response: patients with a CRAFITY score of 0/1 and AFP response (Group 1), those with a CRAFITY score of 2 and no AFP response (group 3), and those who did not belong to Group 1 and 3 (i.e., Group 2). The combination of CRAFITY score and AFP response could predict disease control and could predict PFS compared with CRAFITY score or AFP response alone. The combination of CRAFITY score and AFP response was an independent predictor of OS (Group 2 vs Group 1, HR: 4.513, 95% CI 1.990-10.234; Group 3 vs Group 1, HR: 3.551, 95% CI 1.544-8.168). Our findings indicated that the combination of CRAFITY score and AFP response could predict disease control, PFS, and OS in uHCC patients receiving PD-1 blockade-based immunotherapy.

Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies.

Combined immune checkpoint inhibitors (ICIs) along with tyrosine kinase inhibitors (TKIs) and locoregional therapies have been used increasingly to treat hepatocellular carcinoma (HCC). Biomarkers are required to predict the treatment efficacy of ICIs with or without combination therapies in patients with unresectable HCC. This study enrolled 95 consecutive patients with unresectable HCC from May 2017 to June 2021 from two hospitals retrospectively. Of the 95 patients, 15 and 80 had Barcelona Clinic Liver Cancer stages B and C, respectively. The median ICI treatment duration was 3.43 (1.87-7.87) months, and 77 patients received combination therapies. Radiological imaging was not performed in 13 patients. Objective response and disease control rates were 27.4% and 53.7%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 4.07 (1.59-6.54) months and 14.53 (6.93-22.14) months, respectively. Alpha-fetoprotein (AFP) response was defined as a decline of >15% in the serum AFP level within the initial 3 months of ICI therapy according to Youden's index. AFP response was determined to be a predictor of disease control (odds ratio: 11.657, 95% confidence interval [CI]: 2.834-47.941, P=.001). Macrovascular invasion (MVI), AFP response (hazard ratio [HR]: 0.488, 95% CI: 0.255-0.934, P=.030), combination therapy, and disease control were predictors of PFS, and MVI, AFP response (HR: 0.344, 95% CI: 0.160-0.737, P=.006), and disease control were predictors of OS. AFP response was a predictor of disease control, PFS, and OS. These findings indicate that AFP response can serve as a biomarker to predict treatment outcomes in patients with unresectable HCC receiving ICIs with or without TKIs or locoregional therapies.

Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience.

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.

Evaluation of cost-effectiveness of peginterferon plus ribavirin for chronic hepatitis C treatment and direct-acting antiviral agents among HIV-infected patients in the prison and community settings.

BACKGROUND: In Taiwan, the majority of chronic hepatitis C carriers with HIV co-infection are intravenous drug users and inmates in correctional facilities. Peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (HCV) infection more than decades. We evaluated the estimated cost-effectiveness of PegIFN/RBV from the National Health Insurance Research Database, covering the population of Taiwan from 1998 to 2013. MATERIALS AND METHODS: This is an observational study, and study during was 2010-2016 and a total of 239 patients were treated with PegIFN/RBV. Of them, 156 patients were treated in the correctional facilities of Taipei, Taoyuan, Taichung and Taitung prisons, and 83 patients were treated in communities. The cost-effectiveness was analyzed in regimens of PegIFN/RBV and direct-acting antiviral agents. RESULTS: By multivariate analysis, the patients completed PegIFN/RBV in prison (adjusted odds ratio [aOR]: 4.56, 95% confidence interval [CI]: 1.58-13.12, p = 0.005), HCV RNA level <800,000 IU/mL (aOR: 4.0, 95% CI: 1.27-12.66, p = 0.02) at baseline, and the presence of early virologic response (EVR) (aOR: 7.67, 95% CI: 1.89-31.06, p = 0.004) were independent predictors for sustained virologic response (SVR). For the subgroups of prisoners, HIV-infected prisoners and HIV-infected patients in communities, the SVR rate was 73.8%, 72.0% and 36.8%, and the average medical-care cost was US$7,701, $7,893, and $15,443 per SVR achieved, respectively. Also, the estimated medical-care cost for genotype 6 was US$9211. CONCLUSIONS: Chronic HCV/HIV co-infected patients with genotype 1 and 6 in the community setting could benefit from DAAs in Taiwan.

Increased risk of chronic obstructive pulmonary disease among patients with Helicobacter pylori infection: a population-based cohort study.

BACKGROUND: Increasing evidence suggests that Helicobacter pylori infection (HPI) may have extragastric manifestations, including the respiratory system. This study investigated the role of HPI in increasing the subsequent risk of chronic obstructive pulmonary disease (COPD) in a nationwide population. METHODS: We conducted this retrospective cohort study using data from the Longitudinal Health Insurance Database, which is derived from the Taiwanese National Health Insurance Research Database. A total of 5941 adults who were newly diagnosed with HPI between 2005 and 2006 were selected. Healthy patients without HPI were selected from the general population and frequency matched as a ratio of 4:1, according to age, sex, and index years. Both cohorts were followed up from the index date to the end of 2011 to measure the incidence of COPD. Cox proportional hazard regression analysis was used to assess the hazard ratio (HR) of COPD between the HPI cohort and non-HPI cohorts. RESULTS: The overall HR of COPD was 1.84 (95% confidence intervals = 1.57-2.17) for the HPI cohort, compared with the non-HPI cohort, after adjusting for age, sex, and comorbidities. Although the incidence of COPD was substantially higher in the elderly participants (age, ≥ 65 years) than that in younger participants, the highest HR (4.05, 95% confidence intervals = 1.39-11.8) of COPD was observed in the youngest (age, 20-49 years) participants. CONCLUSION: In this study, the patients with HPI exhibited a significantly higher risk of COPD than those without HPI did.