Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Long-term comparisons of the durability of 6 months versus 12 months antiviral therapy for hepatitis B after chemotherapy cessation.

BACKGROUND: Prophylaxis antiviral therapy is recommended for patients with hepatitis B receiving chemotherapy but the ideal treatment duration after chemotherapy cessation needs more evidence for clarification. AIMS: This study aimed to compare the relapse rate of short finite intervals of 6 months and 12 months of -nucleos(t)ide analogue (NA) therapy in patients stratified by low hepatitis B virus (HBV)-DNA of < 2000 IU/ml or high HBV DNA of ≥ 2000 IU/ml. METHODS: Patients started tenofovir or entecavir treatment 1 week before chemotherapy and were assigned to different treatment duration groups randomly after stratified by HBV DNA pretreatment: (1) HBV DNA of < 2000 IU/ml at 6-month or 12-month duration; (2)HBV DNA of ≥ 2000 IU/ml at 6-month or 12-month duration. Virological relapse (VR) was defined as HBV DNA of > 2000 IU/ml, and clinical relapse (CR) was defined as HBV DNA of > 2000 IU/ml and alanine aminotransferase of > 80 IU/L during the follow-up period. The primary endpoint was to compare the durability between groups 1 year after antiviral therapy cessation. The secondary endpoint was VR and CR rate at long-term follow-up after antiviral therapy cessation. RESULTS: This study enrolled 61 patients, and 5 patients were lost to follow-up or tumor recurrence. VR and CR rates were 46.4% and 14.3% at 1-year and 55.3% and 16.1%, at long-term follow-up, respectively. VR and CR rates demonstrated no difference between the groups. Pretreatment HBV DNA at ≥ 2000 IU/ml and end-of-treatment hepatitis B surface antigen (HBsAg) at ≥ 500 IU/ml were the predictor of VR (hazard ratio [HR]: 2.98; p = 0.010 and HR: 2.38; p = 0.037). CONCLUSIONS: Prolongation from 6 months to 12 months of NA consolidation after chemotherapy cessation did not affect the VR or CR of HBV. High pretreatment HBV DNA and end-of-treatment HBsAg levels could predict VR after antiviral therapy cessation for chemotherapy.

Well-controlled viremia reduces the progression of hepatocellular carcinoma in chronic viral hepatitis patients treated with lenvatinib.

Lenvatinib has been approved as one of the first-line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non-inferior to sorafenib. Previous studies have shown well-controlled viremia contributes to the prognosis of HCC patients receiving first-line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first-line lenvatinib treatment in our institute were assessed. High-effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct-acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV-related HCC (HBV-HCC) and 44 patients with HCV-related HCC (HCV-HCC), respectively. Progression-free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV-HCC patients and 88.4% of the HCV-HCC patients had well-controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well-controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25-0.68, p = 0.001) after adjusting for albumin-bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was.

Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma.

BACKGROUND: Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. METHODS: We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). RESULTS: In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1-2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. CONCLUSION: The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.

Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation.

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.

The Efficacy and Safety of Ramucirumab in Heavily Pretreated Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: Ramucirumab has been approved for the management of hepatocellular carcinoma (HCC) after progression on sorafenib; however, the data on ramucirumab in heavily pretreated HCC are limited. This study aimed to investigate the real-world efficacy and safety of ramucirumab in patients with heavily pretreated advanced HCC. PATIENTS AND METHODS: Patients with advanced HCC who received intravenous ramucirumab as second-line and later therapy were retrospectively reviewed. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Additionally, prognostic factors were estimated using hazard ratios with 95% confidence intervals. RESULTS: In total, 31 patients with advanced HCC who received ramucirumab were enrolled, including 11 patients with second-line treatment and 20 with third-line and later-line treatment. The objective response rate was 3.2% with a disease control rate (DCR) of 45.2%, and the DCR of ramucirumab between the second-line group and the third-line and later-line groups did not differ. The median PFS and OS were 2.1 months and 6.7 months, respectively, in the whole population. In the multivariate analyses, alpha-fetoprotein <1,000 ng/ml was an independent prognostic factor for better PFS and OS. All adverse events were classified as grade 1-2 without grade 3-4 toxicities or drug-related mortality. Additionally, 51.6% of patients received subsequent therapy after progression on ramucirumab. CONCLUSION: The results of our study show the efficacy and safety of ramucirumab in patients with heavily pretreated HCC in real-world practice.

Causes of Death among Patients with Hepatocellular Carcinoma According to Chronic Liver Disease Etiology.

This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality.

Short Half-Life of Des-γ-Carboxy Prothrombin Is a Superior Factor for Early Prediction of Outcomes of Hepatocellular Carcinoma Treated with Radiofrequency Ablation.

BACKGROUND: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. MATERIALS AND METHODS: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. RESULTS: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). CONCLUSIONS: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.

Low-dose nivolumab in advanced hepatocellular carcinoma.

BACKGROUND: The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan-Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child-Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1-2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment. CONCLUSION: Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice.

Well-Controlled Viremia Predicts the Outcome of Hepatocellular Carcinoma in Chronic Viral Hepatitis Patients Treated with Sorafenib.

Without analyzing the status of viremia, hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) patients are proposed to have better prognosis than hepatitis B virus-related HCC (HBV-HCC) patients using sorafenib. We aimed to elucidate the efficacy of concurrent sorafenib and anti-viral treatment for HCC patients with HBV or HCV infection in real world. Between January 2018 and January 2021, 256 unresectable HCC patients receiving first-line sorafenib were evaluated. High-potency nucleoside analogs were used for HBV control, whereas direct-acting antivirals were administered for HCV eradication. Well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before sorafenib. We recruited 116 (65.2%) HBV-HCC patients and 62 (34.8%) HCV-HCC patients. Using sorafenib, progression-free survival and overall survival (OS) rates between these two groups were not different. Before sorafenib, 56% of HBV-HCC patients and 54.8% of HCV-HCC patients had well-controlled viremia and their OS was superior to those who had uncontrolled viremia (15.5 vs. 11.1 months, p = 0.001). Dividing our patients into four subgroups as well-controlled HCV viremia, well-controlled HBV viremia, uncontrolled HCV viremia, and uncontrolled HBV viremia, their OS rates were distributed with a significantly decreasing trend as 21.9 months, 15.0 months, 14.2 months, and 5.7 months (p = 0.009). Furthermore, well-controlled viremia was associated with mortality in multivariate analysis (Hazard ratio: 0.63, 95% confidence interval: 0.42-0.93, p = 0.022). In real-life, HBV or HCV infection did not contribute to the prognosis of HCC patients receiving sorafenib; however, whether viremia was controlled or not did contribute.

Comparison of portal and capsular microscopic vascular invasion in the outcomes of early HCC after curative resection.

Microscopic vascular invasion (MVI) is a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. Two types of MVI are identified: portal vein and capsular vein invasion. However, little is known about the impact of different types of MVI on HCC recurrence. The present study aimed to compare HCC recurrence and OS between the portal vein and capsule vein MVI. Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 were consecutively recruited. Factors that influenced OS and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Of the 857 eligible patients, 327 (38.2%) had MVI, and 530 (61.8%) were without MVI. Of the 327 patients with MVI, 85 (26.0%) were with portal vein, 178 (54.4%) with capsular vein, and 64 (19.6%) with both-MVI type. Patients with both-MVI type suffered from a higher proportion of BCLC stage A (P < 0.001), capsular invasion (P = 0.002), and satellite nodules (P < 0.001). Both-MVI type is an independent risk factor for HCC recurrence (hazard ratio [HR]: 1.69; 95% CI, 1.22-2.36, P = 0.002) and mortality (HR: 2.29; 95% CI, 1.59-3.29, P < 0.001) compared with non-MVI. We further found that both-MVI type was significantly associated with a higher risk of extrahepatic recurrence (EHR) (HR: 8.74; 95% CI, 2.38-32.03, P = 0.001). Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence, especially for EHR, in comparison with non-MVI or only portal or capsular MVI alone.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab.

Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1-2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.

Incorporating albumin-bilirubin grade and up-to-seven criteria to predict outcomes of patients with intermediate stage hepatocellular carcinoma after transarterial (chemo)embolization.

BACKGROUND/PURPOSE: This study is to use albumin-bilirubin (ALBI) grade and up-to-7 (UT7) criteria to assess outcomes of patients with intermediate stage hepatocellular carcinoma (HCC) after transarterial (chemo)embolization (TA(C)E). METHODS: Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TA(C)E were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. RESULTS: A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria (UT7 (-)). There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 (UT7 (+)) and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 -/+, patients were classified into six groups as ALBI grade I plus UT7 (-), II plus UT7 (-), III plus UT7 (-), I plus UT7 (+), II plus UT7 (+), and III plus UT7(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7 (-) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7 (-) and I plus UT7 (+) were ALBI-U class II, and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p < 0.01). CONCLUSION: ALBI-U classification was useful in predicting outcomes of patient with intermediate stage HCC after TA(C)E.

Liver stiffness-based score at sustained virologic response predicts liver-related complications after eradication of hepatitis C virus.

To determine whether liver stiffness (LS) and fibrosis-4 (Fib-4) index were useful in assessing the occurrence of liver-related complications (LRC) in chronic hepatitis C (CHC) patients after direct-acting antivirals (DAAs) had been administered. This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. A total of 697 (male/female: 294/403, mean age: 63.8 year) patients with measured LS and complete lab data at SVR were enrolled, followed, and analyzed. In a median follow-up of 21.4 months after SVR, 39 patients developed LRC including 28 with hepatocellular carcinoma (HCC), with the 30-month cumulative incidence of LRC and HCC being 7.7% and 5.1%, respectively. Predictions of occurrence of LRC and HCC were 0.820 and 0.774 for LS, and 0.775 and 0.737 for Fib-4, with optimal cutoffs of LS and Fib-4 being 14.5 kPa and 2.9 for LRC prediction. In multivariate analysis, LS was associated with the occurrence of LRC (hazard ratio: 3.97, 95% confidence interval [1.866, 8.446], p < 0.001) after adjustment for Fib-4 and diabetes. A risk-score system combining LS, Fib-4, and diabetes was developed for LRC risk assessment. Patients were stratified into low- (score 0-1), intermediate- (score 2-3), and high-risk (score 4) groups with LRC cumulative incidences of 1.7%, 14.9%, and 36.4%, respectively (p < 0.001). For patients with CHC after DAA, the risk scoring system based on LS, Fib-4, and diabetes was useful to assess the risk of LRC development during follow-up; accordingly, it would be advantageous for clinicians to set up more personalized and cost-effective strategies of surveillance.

Corrigendum: Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

[This corrects the article DOI: 10.3389/fonc.2021.737767.].

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BACKGROUND: Lenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world. METHODS: We retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups. RESULTS: A total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3-0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively. CONCLUSIONS: In clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

Hepatic Clostridium Perfringens Abscess Formation after Radiofrequency Ablation Therapy for Hepatocellular Carcinoma: Report of a Rare Case.

Liver abscess formation is one of the major complications following radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). Clostridium perfringens is a rare but fatal (mortality rate: 70-100%) organism that could lead to severe sepsis. We presented a case where a 63-year-old woman with diabetes mellitus, hypertension, chronic hepatitis B-related cirrhosis in Child-Pugh class A and HCC with initial TNM stage II who had undergone 2 sessions of transarterial chemoembolization. RFA was performed for 4 small HCC due to poor effect of previous transarterial chemoembolization. However, all 4 treated tumors developed liver abscesses presenting with septic shock within 1 day. Aspirated abscesses and blood culture both yielded C. perfringens infection. After intensive care, optimal intravenous antibiotic, and abscesses aspiration, the patient recovered successfully. All tumors achieved complete response during the follow-up period without local recurrence. The clinical presentations and risk factors of C. perfringens-related liver abscess after RFA will be discussed in this manuscript.

Sorafenib use in hepatitis B virus- or hepatitis C virus-related hepatocellular carcinoma: A propensity score matching study.

Sorafenib is the recommended first-line treatment option for patients with advanced hepatocellular carcinoma (HCC). Hepatitis C virus (HCV)-related advanced HCC (HCV-HCC) seemed to have a better response than hepatitis B virus (HBV)-related HCC (HBV-HCC) in sorafenib use, but it was undetermined. Hence, we aimed to investigate the effect of sorafenib between HBV-HCC and HCV-HCC patients in Taiwan. From August 2012 to December 2016, 575 consecutive advanced HCC patients received sorafenib under the reimbursement of Taiwan national health insurance in our hospital. Radiologic assessment was performed at a 2-month interval. Those patients with tumor progression or liver function deterioration were disallowed for further sorafenib use. Patients with HBV or HCV infection were, retrospectively, enrolled and followed till December 2018. There were 277 (62.4%) HBV-HCC patients and 167 (37.6%) HCV-HCC patients. Before sorafenib, 192 (69.3%) HBV-HCC patients who had used nucleoside analogs (NAs) for HBV management, whereas only 5 (3%) HCV-HCC patients received interferon-based antiviral therapy. Overall survival (OS) of HCV-HCC patients was significantly superior to HBV-HCC patients without NAs (8.8 months vs. 4.9 months, p = 0.006), but was noninferior to HBV-HCC patients with NAs (8.8 months vs. 10.7 months, p = 0.54). Using propensity score matching, progression-free survival (2.0 months vs. 2.1 months, p = 0.374) and OS (10.5 months vs. 9.6 months, p = 0.746) between HBV-HCC and HCV-HCC groups were not different. Antiviral therapy might increase survival benefits of advanced HBV-HCC patients underwent sorafenib use, leading to a comparable OS to HCV-HCC patients in Taiwan.

Nivolumab Versus Regorafenib in Patients With Hepatocellular Carcinoma After Sorafenib Failure.

BACKGROUND: Nivolumab and regorafenib are approved second-line therapies for patients with hepatocellular carcinoma (HCC) after sorafenib failure. This study compared the effectiveness of nivolumab and regorafenib following sorafenib. METHODS: We retrospectively enrolled HCC patients who had undergone nivolumab or regorafenib after sorafenib failure. Treatment response, treatment-related adverse events (TRAE) and clinical outcomes of study patients were recorded and analyzed. RESULTS: A total of 90 patients (male/female: 67/23, mean age: 63 years) were enrolled, including 32 patients in the Nivolumab group and 58 patients in the Regorafenib group. The Nivolumab group had better objective response rates (16% vs 6.4%) and disease control rates (44% vs 31.9%) than the Regorafenib group, but there was no statistical difference. The comparison of time to progression (3.0 months vs 2.6 months, p=0.786) and overall survival (OS) (14 months vs 11 months, p = 0.763) between Nivolumab and Regorafenib groups were also insignificant. Regarding number of TRAE incidences, the Nivolumab group was significantly lower than the Regorafenib group (37.5% vs 68%). After cession of nivolumab/regorafenib, 34 patients (37.8%) (Nivolumab group/Regorafenib group: 11/23) could afford the following therapies. Concerning sequential systemic therapies, 17 patients (18.9%) received third-line therapy, whereas six patients (6.7%) could move to fourth-line therapy. In multivariable analysis, patients who achieved disease control were associated with improved OS (hazard ratio, 0.18; 95% confidence interval, 0.07-0.46; p<0.001) after adjusting Child-Pugh class and post-treatment. CONCLUSIONS: After sorafenib failure, using nivolumab or regorafenib both illustrated promising treatment outcomes.