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The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of lives, leading to significant morbidity and mortality. With >772 million cases and nearly seven million deaths reported worldwide to date, the development of vaccines has been a critical step in mitigating the impact of COVID-19. However, concerns have arisen regarding the potential for SARS-CoV-2 mRNA vaccination to trigger autoimmune diseases, including autoimmune hepatitis (AIH). The present single-center, retrospective study aimed to compare the clinical and pathological features of AIH in patients with or without a history of SARS-CoV-2 mRNA vaccination. A total of 72 patients with AIH were examined. Among them, 10 had received the SARS-CoV-2 mRNA vaccination prior to AIH onset. These patients exhibited more pronounced CD4+ T cell infiltration into the liver tissue compared with those who were unvaccinated. No significant differences in the levels of other liver enzymes, autoimmune antibodies, or CD8+ T cell infiltration were observed between the groups. Moreover, the AIH patients with a history of SARS-CoV-2 mRNA vaccination had more extensive CD4+ T cell infiltration in their liver tissues than the unvaccinated patients. These findings suggested that the immune response to SARS-CoV-2 mRNA vaccination may influence the pathogenesis of AIH, highlighting the need for further research into the relationship between SARS-CoV-2 mRNA vaccination and autoimmune liver diseases. Such studies will also help clarify the distinction between vaccine-induced liver injury and traditional AIH.
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BACKGROUND/AIM: The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients). RESULTS: The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum α-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002). CONCLUSION: This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Infusiones Intraarteriales , Neoplasias Hepáticas , Vena Porta , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Vena Porta/patología , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Arteria Hepática , Pronóstico , AdultoRESUMEN
Lenvatinib is an approved therapy for advanced hepatocellular carcinoma (HCC). Recently, immune checkpoint inhibitors have been approved as frontline chemotherapies for HCC, and the tumor immune microenvironment (TIME) has been demonstrated to significantly affect HCC treatment. The neutrophil-to-lymphocyte ratio (NLR) is associated with the TIME, and the dynamics of the NLR are associated with prognosis or treatment efficacy in various cancer types. The present study investigated the dynamics of the TIME using the NLR in 101 patients with HCC treated with lenvatinib. Immunostaining for CD8+ tumor-infiltrating lymphocytes (TILs) was also performed in 9 patients who underwent liver tumor biopsy prior to subsequent chemotherapy for progression or discontinuation due to adverse events on lenvatinib treatment. The NLR values measured at the start of treatment (SOT), after 1 month of treatment and after 3 months of treatment were 2.78±2.20, 2.61±1.86 and 2.66±2.36, respectively (P=0.733). Among the patients with no reduction in the initial dose, there was no significant difference between the NLR after 1 month (2.34±0.25) and that at the SOT (2.86±2.33) (P=0.613). In patients who achieved a complete or partial response, the NLR at the time of the best tumor response was 1.65±0.56, which was significantly lower than that at the SOT (2.05±0.78) (P=0.023). In patients who did not respond to lenvatinib, the NLR at the time of disease progression was 3.68±3.19, which was significantly higher than that at the SOT (2.78±1.79) (P=0.043). Overall, 5 out of the 6 patients who did not respond to lenvatinib had low CD8+ TIL counts at disease progression. Although the present study included a limited number of patients, the NLR was associated with the therapeutic effects of lenvatinib. These findings suggest the potential of lenvatinib as an immunomodulator.
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Background/Aim: Numerous agents, including immune checkpoint inhibitors, are now available for hepatocellular carcinoma (HCC) treatment. Most trials involving systemic chemotherapy have included patients with Child-Pugh class A, while excluding or minimally enrolling those with Child-Pugh class B, due to liver dysfunction-related mortality. This study aimed to identify prognostic factors for survival in Child-Pugh class B patients receiving sorafenib (SOR), lenvatinib (LEN), atezolizumab plus bevacizumab (ATZ+BEV), or hepatic arterial infusion chemotherapy (HAIC). Patients and Methods: From December 2003 to June 2023, 137 patients with advanced HCC receiving systemic chemotherapies (SOR: n=43, LEN: n=16, ATZ+BEV: n=18, HAIC: n=60) were enrolled. Results: Overall survival (OS) and response rates did not differ significantly across treatments (SOR: 8.3 months, LEN: 10.2 months, ATZ+BEV: 8.5 months, HAIC: 7.3 months). Patients on HAIC and LEN had a lower rate of discontinuing treatment within three months compared to those on ATZ+BEV and SOR. HAIC was associated with fewer changes in ALBI score and better preservation of liver function. Multivariate logistic regression identified serum α-fetoprotein >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], tumor count >5 (HR=1.55; p=0.043), and Child-Pugh score (HR=2.53; p=0.002) as independent predictors of OS. Conclusion: OS and response rates were similar across systemic chemotherapies. Prognosis for HCC in Child-Pugh class B patients was associated with liver function, necessitating further research for optimal treatment.
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Background/Aim: Atezolizumab in combination with bevacizumab is an approved systemic chemotherapy regimen for advanced hepatocellular carcinoma (HCC). However, immune checkpoint inhibitors (ICIs), such as atezolizumab, frequently lead to immune-related adverse events (irAEs). The identification of biomarkers that can predict the occurrence of irAEs is crucial for the optimal management of patients undergoing ICI treatment. Patients and Methods: Between October 2020 and June 2023, we conducted a study involving 69 patients with advanced HCC who received treatment with atezolizumab plus bevacizumab. We conducted an analysis of blood-based biomarkers to identify independent risk factors associated with irAEs. Results: In our study, 12 out of 69 patients (17.4%) experienced irAEs. Our investigation into blood-based biomarkers revealed that a neutrophil-to-lymphocyte ratio (NLR) <2.04 at three weeks after the initiation of treatment had high predictive power (area under the curve: 0.77) for irAEs. Furthermore, multivariate logistic analysis identified NLR at three weeks (hazard ratio=0.23; p=0.037) and non-viral infection (hazard ratio=4.47; p=0.037) as independent factors contributing to the occurrence of irAEs. Patients who developed irAEs demonstrated a more favorable overall response rate (75.0% vs. 28.1%, p=0.005), disease control rate (91.6% vs. 52.6%, p=0.016), and progression-free survival (12.1 months vs. 6.0 months, p=0.010) than those who did not experience irAEs. Conclusion: An NLR <2.04 at three weeks after the initiation of treatment may serve as a valuable biomarker for predicting irAEs in patients with HCC undergoing atezolizumab plus bevacizumab therapy.
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Background/Aim: In radiofrequency ablation (RFA) treatment of hepatocellular carcinoma (HCC), the therapeutic effect depends on the appropriate position of the electrode. To improve the accuracy of the electrode needle position, we currently perform RFA with combined ultrasound sonography (US) and computed tomography (CT) guidance. The purpose of this study was to evaluate the effectiveness of this US/CT-guided RFA method. Patients and Methods: This retrospective study recruited 97 patients with single tumors treated with transcatheter arterial chemoembolization and monopolar RFA between January 2013 and December 2017. Among these, 50 patients were treated with RFA under US/CT guidance (US/CT-guided group) and 47 were treated with RFA under US guidance alone (US-guided group). We analyzed the efficacy of US/CT guidance compared with US guidance alone. Results: The 1-, 2-, and 3-year local recurrence rates for the US/CT-guided and US-guided groups were 4.1%, 6.3%, and 8.6%, and 19.6%, 31.6%, and 41.9%, respectively. The local recurrence rate was lower in the US/CT-guided group (p=0.0030). Cox proportional hazards model for multivariate analysis demonstrated that the independent risk factors associated with local recurrence were tumor size (p=0.0028) and US/CT guidance (p=0.0037). Conclusion: US/CT-guided RFA for HCC reduced the local recurrence rate compared with US-guided RFA alone.
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In the systemic drug treatment of hepatocellular carcinoma, only the tyrosine kinase inhibitor (TKI) sorafenib was available for a period. This was followed by the development of regorafenib as a second-line treatment after sorafenib, and then lenvatinib, a new TKI, proved non-inferiority to sorafenib and became available as a first-line treatment. Subsequently, cabozantinib, another TKI, was introduced as a second-line treatment, along with ramucirumab, the only drug proven to be predictive of therapeutic efficacy when AFP levels are >400 ng/mL. It is an anti-VEGF receptor antibody. More recently, immune checkpoint inhibitors have become the mainstay of systemic therapy and can now be used as a first-line standard treatment for HCC. However, the objective response rate for these drugs is currently only 30% to 40%, and there is a high incidence of side effects. Additionally, there are no practical biomarkers to predict their therapeutic effects. Therefore, this review provides an overview of extensive research conducted on potential HCC biomarkers from blood, tissue, or imaging information that can be used in practice to predict the therapeutic efficacy of systemic therapy before its initiation.
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Current antiviral therapies cannot achieve eradication of hepatitis B virus (HBV) and can reduce but not eliminate the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. The present study aimed to identify the risk factors for HCC development by analyzing nucleoside analogue (NA)-treated patients as a retrospective cohort using fibrosis-4 index (FIB-4 index) as a non-invasive fibrosis marker. A total of 260 patients with HBV receiving NAs without a history of HCC between January 2001 and January 2021 were included in the present study. The incidence of HCC in patients with HBV during NA therapy and the factors contributing to HCC occurrence were identified using clinical characteristics and blood test results. Among the 260 patients, 40 patients (15.4%) developed HCC. Univariate and multivariate analysis showed that age [hazard ratio (HR), 1.03; P=0.045], male sex (HR, 3.14; P<0.01) and FIB-4 index at 6 months after NA treatment <1.95 (HR, 4.35; P<0.01) correlated with the incidence of HCC. The cumulative incidence of HCC in patients with FIB-4 index at 6 months after NA treatment >1.95 was significantly higher compared with that in patients with FIB-4 index ≤1.95 (P<0.01). Multivariate analysis in patients in which serum α-fetoprotein (AFP) level at 6 months after NA treatment was measured showed that FIB-4 index >1.95 (HR, 8.27; P=0.014) and serum AFP level >4 ng/ml (HR, 4.26; P=0.033) contributed to HCC occurrence. FIB-4 index at 6 months after NA treatment and serum AFP levels at 6 months after NA treatment were predictors for the development of HCC in patients with HBV during NA treatment. Further study of hepatocarcinogenesis during NA with a longer follow-up period and larger numbers of participants is required.
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BACKGROUND/AIM: Systemic chemotherapy with atezolizumab plus bevacizumab is approved for unresectable hepatocellular carcinoma (HCC). It is necessary to identify probable predictive biomarkers for chemotherapies. HCC with rim arterial-phase enhancement (APHE) has been linked to aggressive tumor activity. PATIENTS AND METHODS: We studied the efficacy of atezolizumab plus bevacizumab for HCC using computed tomography (CT) or magnetic resonance imaging (MRI) imaging features. In total, 51 HCC patients who underwent CT or MRI were classified by the feature of rim APHE. RESULTS: Clinical responses to chemotherapy were evaluated, and among those who received atezolizumab plus bevacizumab, there were 10 (19.6%) patients with rim APHE and 41 (80.4%) patients without rim APHE. We found that patients with rim APHE had a better response than those without rim APHE, and patients with rim APHE had longer median progression-free survival compared with those without rim APHE (p=0.026). Furthermore, liver tumor biopsy showed that HCC with rim APHE had a higher proportion of CD8+ tumor-infiltrating lymphocytes (p<0.01). CONCLUSION: Rim APHE in CT/MRI imaging might be a noninvasive biomarker for predicting response to atezolizumab plus bevacizumab.
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Atezolizumab plus bevacizumab and lenvatinib are approved frontline therapies for advanced hepatocellular carcinoma (HCC). Patients with advanced HCC continue to have a poor prognosis despite these therapeutic choices. Previous studies have reported CD8+ tumor-infiltrating lymphocytes (TILs) as a biomarker to predict responsiveness to systemic chemotherapy. The present study investigated whether evaluating CD8+ TILs by immunohistochemistry staining of liver tumor biopsy tissues could help predict the response of patients with HCC to atezolizumab plus bevacizumab and lenvatinib. In total, 39 patients with HCC who underwent liver tumor biopsy were classified into high and low CD8+ TILs groups and were then divided by therapy type. The clinical responses to treatment in both groups were evaluated for each therapy. There were 12 patients with high-level CD8+ TILs and 12 patients with low-level CD8+ TILs among those who received atezolizumab plus bevacizumab. An improved response rate was observed in the high-level group compared with the low-level group. The high-level CD8+ TILs group had a significantly longer median progression-free survival compared with the low-level group. Among the patients with HCC who received lenvatinib, five had high-level CD8+ TILs and 10 had low-level CD8+ TILs. There were no differences in response rate or progression-free survival between these groups. Although the present study included only a limited number of patients, the findings suggested that CD8+ TILs could be a biomarker for predicting response to systemic chemotherapy in HCC.
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Background and Aim: Direct-acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection. Additionally, interferon-free DAA treatment has improved liver function and reduced the risk of hepatocellular carcinoma (HCC) following HCV eradication. Previous studies on HCV have focused mainly on the treatment rate and the risk of developing HCC, and less attention has been given to loss to follow-up (LTFU) after DAA treatment. Therefore, the present study aimed to identify the definitive risk factors for LTFU after the start of DAA treatment. Methods: Between September 2017 and March 2022, 296 patients receiving glecaprevir and pibrentasvir for HCV infection were enrolled in this study. The incidence of LTFU following DAA treatment and the risk factors contributing to LTFU were identified using the patients' clinical characteristics. Results: In the present study, 75 patients (25.3%) interrupted their follow-up visits. Multivariate logistic analysis revealed a history of injection drug use (hazard ratio [HR], 1.81; P = 0.017), treatment duration (8 weeks) (HR, 3.51; P = 0.0033), and age <70 years (HR, 1.9; P = 0.0422) as independent factors associated with LTFU after the start of DAA treatment. Conclusion: Young patients and those with injection drug use are likely to discontinue their follow-up visits after the start of DAA treatment for HCV infection. Therefore, these patients require strict supervision.
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AIM: Cabozantinib showed a favorable benefit-risk profile in Japanese patients with advanced hepatocellular carcinoma (HCC) in an open-label, phase II study (NCT03586973). This analysis presents cumulative data to final database lock. METHODS: Patients with previously treated, advanced HCC received cabozantinib 60 mg/day. Progression-free survival (PFS) and tumor response rates in prior-sorafenib and sorafenib-naïve cohorts were assessed by independent radiology committee (IRC) and an investigator. Liver function was evaluated by albumin-bilirubin (ALBI) score. RESULTS: Median cabozantinib exposure was 5.6 months. In the prior-sorafenib cohort (n = 20), median PFS was 7.4 months per IRC assessment and 5.6 months per investigator assessment. In the sorafenib-naïve cohort (n = 14), median PFS was 3.6 and 4.4 months per IRC and investigator assessment, respectively. Six-month PFS rate per IRC and investigator assessment in the prior-sorafenib cohort was 59.8% and 49.5%, respectively, and in the sorafenib-naïve cohort was 16.7% and 35.7%, respectively. Disease control rate by both IRC and investigator assessment was 85.0% in the prior-sorafenib cohort and 64.3% in the sorafenib-naïve cohort. Median overall survival (Kaplan-Meier estimate) was 19.3 and 9.9 months in the prior-sorafenib and sorafenib-naïve cohort, respectively. Mean ALBI score remained relatively constant in patients able to continue treatment. The most frequent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension, and decreased appetite. No new safety concerns were identified. CONCLUSIONS: Cabozantinib showed efficacy and a manageable safety profile in Japanese patients with advanced HCC.
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BACKGROUND: Lenvatinib was approved for use in unresectable hepatocellular carcinoma (uHCC) in Japan in 2018. Patients with diverse clinical characteristics receive lenvatinib treatment in clinical practice. Thus, it is crucial to evaluate the safety and effectiveness of lenvatinib in real-world clinical settings. OBJECTIVE: This study aimed to evaluate the real-world safety and effectiveness of lenvatinib for uHCC in clinical practice in Japan. PATIENTS AND METHODS: Between July 2018 and January 2019, patients with uHCC who were administered lenvatinib for the first time were enrolled in this prospective, multicenter, observational post-marketing study (NCT03663114). Patients were orally administered lenvatinib and followed up for 12 months. For safety, adverse drug reactions (ADRs) were evaluated. For effectiveness, the objective response rate (ORR) was calculated to evaluate tumor response. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: Data of 703 patients (median age, 73 years; 80.2% males) were analyzed. The median (range) treatment duration was 25.3 (0.3-68.9) weeks. The mean ± standard deviation initial dose was 7.37 ± 1.65 mg in patients with body weight < 60 kg and 10.43 ± 2.49 mg in those with body weight ≥ 60 kg. ADRs (any grade) were reported in 84.9% of the patients, with Grade ≥ 3 ADRs reported in 42.5% of the patients. The most common ADRs (> 10%) were decreased appetite, fatigue, hypertension, proteinuria, palmar-plantar erythrodysesthesia, hypothyroidism, and diarrhea. The median OS of the 703 patients was 498.0 days. In 494 patients assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the ORR was 39.5% (95% confidence interval: 35.1-43.9%). Patients with better liver or renal function at baseline achieved significantly higher ORR than those with worse liver or renal function. CONCLUSIONS: In patients with uHCC in real-world clinical practice in Japan, treatment with lenvatinib was generally well tolerated, and no new safety concerns were identified. The ORR and median OS were similar to or better than the results of the Japanese subset of the global Phase III REFLECT trial. Our results demonstrated that clinically meaningful treatment responses were achieved with lenvatinib in real-world clinical practice.
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Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP) >400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. Results The median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Sorafenib/uso terapéutico , alfa-Fetoproteínas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Pronóstico , Bilirrubina , Estudios Retrospectivos , RamucirumabRESUMEN
To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Bevacizumab/efectos adversos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Terapia Molecular Dirigida , Compuestos de Fenilurea , Quinolinas , Sorafenib/uso terapéuticoRESUMEN
A 61-year-old man was admitted due to alcoholic liver cirrhosis, portal vein thrombosis, hepatocellular carcinoma, and chronic pancreatitis. The patient's portal vein thrombosis improved with anticoagulant therapy. Serum amylase gradually increased, but there was no abdominal pain. The patient was placed under observation. The pain in both ankle and knee joints appeared on nine days after admission. Multiple osteonecrotic lesions of both elbows, both knees and both ankle joints were examined using 99mTc bone scintigraphic examinations. Magnetic resonance of the right ankle joint showed osteonecrosis. The pain of the right ankle joint improved with a decrease of serum amylase. We report that this is a rare case of multiple osteonecrosis caused by exacerbation of chronic pancreatitis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Osteonecrosis , Pancreatitis Crónica , Trombosis de la Vena , Amilasas , Carcinoma Hepatocelular/complicaciones , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Osteonecrosis/complicaciones , Osteonecrosis/diagnóstico por imagen , Dolor/complicaciones , Pancreatitis Crónica/complicaciones , Vena Porta , Trombosis de la Vena/complicacionesRESUMEN
Atezolizumab plus bevacizumab therapy has high response rates in patients with advanced hepatocellular carcinoma (HCC). It has been reported that HCC with immune exclusion associated with the signal activation of WNT/ß-catenin is resistant to immune checkpoint inhibitors; however, to the best of our knowledge, the effectiveness of atezolizumab plus bevacizumab for HCC with WNT/ß-catenin signal activation has not been reported. The present study aimed to analyze the efficacy of atezolizumab plus bevacizumab for HCC with WNT/ß-catenin signal activation. A total of 24 patients who underwent liver tumor biopsy for HCC were classified into WNT/ß-catenin signal activation and inactivation groups according to the expression levels of ß-catenin and glutamine synthetase, which are indicative of WNT/ß-catenin signal activation. The differences in the clinical responses to treatment between the groups were analyzed. A total of 15 patients had HCC with WNT/ß-catenin signal activation, whereas 9 patients had HCC with WNT/ß-catenin signal inactivation. There were no significant differences between both groups regarding objective responses (P=0.519) and disease control (P=0.586). In the WNT/ß-catenin signal activation group, the median progression-free survival rate was 6.9 months compared with 6.2 months in the WNT/ß-catenin signal inactivation group (P=0.674). Although a small number of patients was included in the present study, the present findings suggested that the efficacy of atezolizumab plus bevacizumab might be unaffected by WNT/ß-catenin signal activation.
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The risk of hepatocellular carcinoma (HCC) occurrence following hepatitis C virus (HCV) eradication has been previously reported, but the impact of HCV eradication on advanced HCC patient survival remains unclear. Therefore, the present study aimed to evaluate the effect of HCV eradication on the survival outcome of patients with advanced HCC treated with sorafenib. One hundred and three HCV-related advanced HCC patients who were treated with sorafenib were enrolled in this study. Of these, 43 patients were administered antiviral therapy before sorafenib treatment (HCV eradication group), while 60 patients remained HCV-infected (HCV non-eradication group). We analysed the impact of HCV eradication on survival in advanced HCC treated with sorafenib. Median overall survival (OS) was significantly longer in the HCV eradication group than in the HCV non-eradication group (24.0 months vs. 14.1 months; p = 0.001). Although there was no significant difference in the albumin-bilirubin (ALBI) score at the start of treatment between the HCV eradication group and the non-eradication group (p = 0.065), the ALBI score at 2 months after initiation of sorafenib treatment was significantly decreased in the HCV non-eradication group (p < 0.001), but not in the HCV eradication group (p = 0.121). Multivariate logistic analysis revealed HCV eradication (hazard ratio [HR], 0.5; p = 0.006) and ALBI score at the start of treatment (HR, 2.47; p = 0.002) as factors that may contribute to OS. HCV eradication may serve an important role in the survival outcome of advanced HCC patients treated with sorafenib.
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Antineoplásicos , Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Bilirrubina , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/patología , Pronóstico , Estudios Retrospectivos , Sorafenib/uso terapéuticoRESUMEN
BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) rarely recurs in a multicentric manner. We encountered a patient with multiple recurrences of the gastric subtype of IPNB one year after spontaneous detachment of the primary tumor during peroral cholangioscopy (POCS). CASE SUMMARY: A 68-year-old woman on maintenance hemodialysis because of lupus nephritis had several cardiovascular diseases and a pancreatic intraductal papillary mucinous neoplasm (IPMN). She was referred to our department for dilation of the common bile duct (CBD) and a tumor in the lumen, detected using ultrasonography. She had no complaints, and blood tests of hepatobiliary enzymes were normal. Magnetic resonance cholangiopancreatography (MRCP) showed a papillary tumor in the CBD with a filling defect detected using endoscopic retrograde cholangiography (ERC). Intraductal ultrasonography revealed a papillary tumor and stalk at the CBD. During POCS, the tumor spontaneously detached with its stalk into the CBD. Pathology showed low-intermediate nuclear atypia of the gastric subtype of IPNB. After 1 year, follow-up MRCP showed multiple tumors distributed from the left hepatic duct to the CBD. ERC and POCS showed multicentric tumors. She was alive without hepatobiliary symptoms at least two years after initial diagnosis of IPNB. CONCLUSION: The patient experienced gastric subtype of IPNB without curative resection. Observation may be reasonable for patients with this subtype.