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Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

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Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.

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Linear immunoglobulin A bullous dermatosis (LABD) is a rare immune-mediated vesiculobullous disease that is reported to be induced by infections or medications. Atezolizumab is a monoclonal antibody that targets programmed cell death ligand-1 and has been used to treat multiple cancers. Here, we report a case of drug induced LABD following the administration of Atezolizumab.

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Background: The therapeutic landscape of unresectable hepatocellular carcinoma (uHCC) continues to evolve. Atezolizumab, an anti-programmed cell death ligand 1 (PD-1) immune checkpoint inhibitor (ICI), in combination with bevacizumab, has substantially improved outcomes. This study aims to evaluate the incidence, risk factors, and outcomes in patients who develop infections while receiving atezolizumab and bevacizumab for uHCC. Methods: Patients who received atezolizumab and bevacizumab for uHCC at a single hospital network were included. Types and rates of infections were reported. Covariates compared among infected and non-infected cohorts included age, sex, race, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, immunosuppressive use, chronic infections, number of cycles of ICIs given, antibiotic or antiviral therapies at ICI initiation, and line of therapy (first-line, second-line, greater than second-line). Results: Out of 810 evaluable patients, 34 uHCC patients were treated with atezolizumab plus bevacizumab. The mean ± SD age was 66.29 ± 9.39; 28 (82.35%) were males. There were 17 (50%) patients with reported infection, with bacterial infection occurring in 12 (70.59%) patients and COVID-19 in 4 (23.5%). Of the infected patients, eight (47.06%) had one infection, five (29.41%) had two infections, and two (11.76%) had three or more infections. Infected and non-infected patients received a median of 12 (IQR: 5-17) and 4 (IQR: 3-12) ICI cycles (p = 0.18), respectively. Infections did not negatively impact OS or PFS but resulted in treatment delays and discontinuation in 11 (64.71%) and 7 (41.18%) patients, respectively. At the last follow-up, 19 (55.88%) patients died, 9 (52.94%) in the non-infected group vs. 10 (58.82%) in the infected group (p = 1.0). Conclusions: While a broad array of infections occurred in 50% of the patients in this cohort, it did not negatively impact survival outcomes. However, it did impact morbidity, with more all-cause admissions and treatment delays.

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Background: Pyogenic liver abscess (PLA) could be fatal even after standard treatment with antibiotics and percutaneous drainage. Immune checkpoint inhibitors, bevacizumab or microwave ablation may cause PLA, respectively. This paper presents the first case of PLA secondary to the concomitant use of microwave ablation with atezolizumab and bevacizumab in the treatment of liver cancer. Case Description: A 54-year-old Chinese man with Barcelona Clinic Liver Cancer (BCLC) C-stage liver cancer complained of fever and chills twenty-nine days after concurrent microwave ablation plus atezolizumab and bevacizumab. Post-hospitalization, a computed tomography revealed a rim-enhancing hypodensity within the right lobe of the liver, approximately 8.8 cm in diameter containing foci of gas. Laboratory examination revealed elevated white blood cell count, C-reactive protein and procalcitonin, and blood culture indicated the presence of Escherichia coli bacteremia. The patient was diagnosed with PLA complicated by septic shock, and due to recurrent fever, multiple courses of antibiotics (imipenem/cilastatin sodium, cefoperazone/sulbactam, meropenem, respectively) were administered in combination with five percutaneous drainages over the next 90 days. The patient's fever eventually resolved, and the patient was discharged. The patient was re-treated with two cycles of atezolizumab and bevacizumab initiated in March 2024. An imaging evaluation in May 2023 demonstrated tumor progression. Subsequently, the patient underwent one transarterial chemoembolization procedure and two cycles of atezolizumab and bevacizumab over the subsequent 2 months. Notably, the patient achieved a complete response at the July 2024 imaging evaluation. Conclusions: In patients undergoing atezolizumab and bevacizumab, the potential risk of PLA versus the antitumor benefit of microwave ablation requires to be assessed. The use of multiple courses of antibiotics over a prolonged period did not appear to influence the effectiveness of atezolizumab and bevacizumab. Further studies are, however, needed to substantiate this finding.

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Immune checkpoint inhibitors (ICIs) are pivotal in managing metastatic non-oncogene addicted non-small-cell lung cancer (NSCLC). They have unique toxicities known as immune-related adverse events (irAEs). Previous studies have linked irAEs during atezolizumab-based first-line treatments in advanced NSCLC with improved outcomes. This study explored the association between irAEs and the efficacy of atezolizumab in advanced NSCLC patients who had previously received platinum-based chemotherapy. The study involved 105 advanced NSCLC patients who received atezolizumab monotherapy after progressing on at least one line of platinum-based chemotherapy from a single academic institution in Serbia. Data were obtained from a hospital lung cancer registry. Among the participants, 63.8% were male, with the majority being current (53.3%) or former smokers (37.1%). About half had a good performance status (ECOG PS 0-1) at the start of atezolizumab treatment. irAEs occurred in 23 patients (21.9%). The median progression-free survival (mPFS) was significantly longer for patients with irAEs (13.03 months) compared to those without (3.4 months) (HR 0.365 [95% CI, 0.195-0.681], p = 0.002). irAEs and ECOG PS 0-1 were predictors of longer mPFS, with irAEs being more common in patients with good performance status (p = 0.01). irAEs were linked to improved mPFS in NSCLC patients treated with atezolizumab after multiple lines of platinum-based chemotherapy.

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Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in Asian populations (2013-2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening the titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. A total of 60 clinical trials fulfilled our inclusion criteria with 36 drugs used as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicates that sorafenib, used alone or in combination with atezolizumab and bevacizumab, has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in Asian populations.

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A 65-year-old man treated with atezolizumab plus bevacizumab for hepatocellular carcinoma was admitted to our hospital with a fever, difficulty in moving, and aphasia. The patient became comatose immediately after admission. Imaging and cerebral fluid tests revealed no evidence of malignancy or infection. A diagnosis of atezolizumab-induced encephalitis was made, and steroid pulse therapy was initiated on admission, immediately after which the patient regained consciousness and was able to talk and walk. He was discharged with slight paralysis of his legs and was able to resume chemotherapy. An early diagnosis and treatment are required to improve the prognosis of encephalitis.

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Background/Aim: Atezolizumab/bevacizumab (atez/bev) has been established as first-line systemic treatment for hepatocellular carcinoma (HCC). However, concerns regarding safety and efficacy have been raised, and no biomarkers to predict response have yet been identified. We aimed to evaluate the real-life experience of atez/bev in a Spanish tertiary hospital and identify factors associated with overall survival (OS). Patients and Methods: A prospective study of consecutive patients with HCC treated with atez/bev was conducted from December 2020 to December 2022. Efficacy was assessed through OS and progression-free survival (PFS), whereas safety was evaluated based on adverse events (AE). Twenty-three patients were included; 91% were males with a mean of 70 years. Thirteen patients were classified as having BCLC-C. Results: The median treatment duration was 126 days (range=567). Median OS was 381 days (95%CI=205-557) with a cumulative probability of death of 13%, 30%, and 49% at 3, 6 and 12-month follow-up, respectively. The only factor associated with OS was the ALBI score (HR=5.03; 95%CI=1.3-19.1), which showed an AUROC of 0.906 (95%CI=0.78-1.00) for the risk of death at 18 months follow up. Median PFS was 141 days (95%CI=110-172). Twenty (86.9%) patients experienced AE, which in nine (39.1%) cases led to the definitive discontinuation of the treatment, four of them (17.4%) due to an AE grade 5. Conclusion: The initial experience with atez/bev at our center demonstrated poorer outcomes compared to the original trial (IMbrave150). A careful assessment of the ALBI score may serve as a crucial factor in the selection of systemic treatment for patients with HCC.

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Introduction. Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide.Gap statement. Monitoring of HCC and predicting its immunotherapy responses are challenging.Aim. This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses.Methods. DNA samples were collected from the faeces of 22 patients with HCC treated with atezolizumab/bevacizumab (Atz/Bev) and 85 healthy controls. The gut microbiome was analysed using 16S rRNA next-generation sequencing and quantitative PCR (qPCR).Results. The microbiomes of patients with HCC demonstrated significant enrichment of Lactobacillus, particularly Lactobacillus fermentum, and Streptococcus, notably Streptococcus anginosus. Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of Bacteroides stercoris in the NR group and Bacteroides coprocola in the R group. Using qPCR analysis, we observed elevated levels of S. anginosus and reduced levels of 5α-reductase genes, essential for the synthesis of isoallolithocholic acid, in HCC patients compared to controls. Additionally, the analysis confirmed a significantly lower abundance of B. stercoris in the Atz/Bev R group relative to the NR group.Conclusions. The gut microbiome analysis and specific gene quantification via qPCR could provide a rapid, less invasive, and cost-effective approach for assessing the increased risk of HCC, monitoring patient status, and predicting immunotherapy responses.

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Immune checkpoint inhibitor (ICI)-related type 1 diabetes is an immune-related adverse event (irAE), occurring in slightly less than 1% of patients undergoing ICI therapy. Most cases develop during ICI treatment, with occurrences long after discontinuation being extremely rare. A 76-year-old woman, with no history of glucose tolerance issues, was diagnosed with lung adenocarcinoma with pleural invasion and underwent chemotherapy, including atezolizumab, an anti-programmed death-ligand 1 antibody. This treatment was discontinued due to disease progression, although she continued with other chemotherapy regimens. Approximately 5.5 months (166 days) after her last atezolizumab dose, she developed diabetic ketoacidosis, fulfilling the diagnostic criteria for fulminant type 1 diabetes. Anti-glutamic acid decarboxylase antibodies were positive. The patient carried susceptibility human leukocyte antigen (HLA) haplotypes, which are associated with type 1 diabetes. To date, including our patient, only nine cases of ICI-related type 1 diabetes developed after ICI discontinuation have been precisely reported. Eight cases originated from East Asia, with six exhibiting fulminant type 1 diabetes, and seven tested negative for islet-related autoantibodies. The reported cases were independent of ICI types, cycle number, or HLA haplotypes. Median time from the last ICI administration to diabetes onset was 4 months (range: 2-7 months). Although reports of cases occurring after ICI discontinuation are currently limited, their frequency may increase with the wider use of ICIs and improved survival rates of patients post-treatment. Therefore, it is crucial to remain vigilant for the development of ICI-related type 1 diabetes, not only during ICI administration, but also long after discontinuation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00719-4.

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INTRODUCTION: In 2021, the LEOPARD trial reported that the combination of lenvatinib+one-shot cisplatin infusion might contribute to improving the results of conventional advanced hepatocellular carcinoma (HCC) treatment. Thus, combination therapy with lenvatinib and catheterization has emerged as a focal point in treating advanced HCC. Conversely, the New FP regimen consists of low-dose cisplatin (CDDP) combined with 5-fluorouracil (5-FU) and lipiodol via hepatic arterial infusion chemotherapy (HAIC), with a high response rate of approximately 70%. Therefore, lenvatinib+New FP (LEN-New FP) may be a more promising treatment for HCC. Here, we report six patients who were administered LEN+New FP and achieved high therapeutic efficacy. Among them, one case had an interesting clinical course, which has been described in detail. MATERIALS AND METHODS: This study included six patients who were administered 12 mg or 8 mg of lenvatinib once daily based on a body weight of ≥60 kg or <60 kg, respectively, along with 50 mg of cisplatin in 5-10 mL lipiodol, and a continuous infusion of 5-FU (1500 mg/5 days) infused every 2-4 weeks. Tumor evaluations were performed 4-8 weeks after the initiation of New FP administration and every 8-12 weeks thereafter. RESULTS: The median patient age was 65 years. All patients had a history of prior treatment with atezolizumab and bevacizumab and one of the factors associated with poor overall survival for New FP monotherapy, such as a maximum tumor diameter ≥7 cm and bilobular multifocal distribution. Four (67%) patients had severe vascular invasion. The best objective response and disease control rates were 83% and 100%, respectively. The best response of the target lesion was complete remission in four out of six patients. CONCLUSION: The LEN-New FP combination for advanced HCC showed a high response rate and was more effective in high-risk patients with factors associated with poor overall survival than that reported with conventional New FP monotherapy. Additionally, LEN-New FP exhibited extremely high objective response and disease control rates and was well tolerated, including in cases where it was considered second- or third-line systemic chemotherapy for advanced HCC. Thus, LEN-New FP can serve as a breakthrough therapy for advanced HCC based on appropriate case selection.

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Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy.

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BACKGROUND: Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma (HCC), with ongoing real-world implementation to study its effectiveness. As the use of atezolizumab/bevacizumab increases, various side effects have been reported in clinical practice, most notably increased bleeding caused by bevacizumab. CASE SUMMARY: In this case report, we present a rare and fatal case of intratumoral hemorrhage in a patient with advanced HCC following successful treatment with atezolizumab/bevacizumab. A 63-year-old male diagnosed with HCC initially underwent four cycles of intra-arterial chemotherapy. However, follow-up abdominal computed tomography (CT) revealed disease progression. Subsequently, the treatment plan was modified to atezolizumab/bevacizumab. After the fifth cycle of atezolizumab/bevacizumab, CT showed partial regression of HCC. One week later, he visited the emergency room due to severe abrupt abdominal pain. Abdominal CT revealed focal rupture of HCC in the medial segment inferior portion with active bleeding and a large amount of hemoperitoneum. Angiography was performed on the same day, and embolization of A4 and A8 branches using lipiodol and gelfoam was implemented. Despite successful hemostasis, the patient subsequently developed liver failure and died. CONCLUSION: Atezolizumab/bevacizumab for advanced HCC suggests that intratumoral hemorrhage may be crucial despite good tumor response after immunotherapy, emphasizing the continuous monitoring of this side effect.

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Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

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Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.

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OBJECTIVES: This exploratory integrated analysis of the randomized Phase III IMpower130 and IMpower132 trials evaluated the efficacy and safety of atezolizumab plus platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) who were aged ≥75 years or had renal dysfunction. MATERIALS AND METHODS: Chemotherapy-naïve patients with stage IV non-squamous NSCLC received atezolizumab-containing therapy or platinum-doublet chemotherapy in IMpower130 and IMpower132. This integrated analysis assessed efficacy (including overall survival [OS], progression-free survival [PFS], and objective response rates) and safety in the integrated population and in patients ≥75 years old. Subgroup analyses by baseline creatinine clearance (<45, 45 to <60, and ≥60 mL/min) were conducted for each study population. RESULTS: This integrated analysis included 1224 patients: 737 in the atezolizumab-containing group and 487 in the chemotherapy group. At data cutoff, the hazard ratio (HR) for PFS was 0.62 (95% CI: 0.54-0.71) in the integrated population and 0.59 (95% CI: 0.40-0.88) in the ≥75-years subgroup. The HR for OS was 0.81 (95% CI: 0.68-0.95) in the integrated population and 0.65 (95% CI: 0.39-1.07) in the ≥75-years subgroup. PFS and OS benefits with the atezolizumab combination vs chemotherapy were maintained across subgroups with varying renal function in IMpower130, and PFS benefits were maintained across subgroups in IMpower132. CONCLUSIONS: The results of this post hoc integrated analysis of IMpower130 and IMpower132 show that the efficacy and safety of atezolizumab plus platinum-doublet chemotherapy is maintained in patients ≥75 years old and in patients with renal dysfunction.

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Bleeding-related adverse events may occur due to anti-vascular endothelial growth factors. Here, we report two cases of variceal rupture during atezolizumab plus bevacizumab (ATZ/BV) treatment for unresectable hepatocellular carcinoma (u-HCC).Case 1 involved a man in his 60 s with alcoholic liver cirrhosis (LC) and u-HCC. Seventy-four days after ATZ/BV administration, the patient was admitted for hematemesis. Upper esophagogastroduodenoscopy (EGD) revealed worsening of the esophageal varices (EVs) to F2 grade with active bleeding. Endoscopic variceal ligation successfully achieved hemostasis.Case 2 involved a man in his 70 s with alcoholic LC and u-HCC. The patient was admitted with hematemesis 114 days after ATZ/BV administration. During EGD, the EVs deteriorated to F3 grade, although hemostasis had already been achieved. The evaluation was discontinued during the observation stage because of the worsening hepatic reserve.Neither patient had EVs warranting prophylactic treatment before ATZ/BV administration, showed a partial tumor response, or had portal vein tumor thrombus. Both patients demonstrated increased total diameters of the collateral veins and splenic volume compared to those before treatment. These findings suggest that ATZ/BV treatment may increase portal pressure. In conclusion, the administration of ATZ/BV to patients with LC and u-HCC necessitates careful management of EVs aggravation and rupture.

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A woman in her early 80 s was followed up in our hospital for chronic hepatitis C after viral eradication. We detected rapid-growing lymph node metastasis of hepatocellular carcinoma (HCC) after treatment with transcatheter arterial chemoembolization and/or radiofrequency ablation. We found that the metastasis was operable, but the size and location of the metastasis obliged the patient to receive pancreatoduodenectomy, which was too invasive. Then we initiated systemic chemotherapy to perform radical minimally invasive surgery. We treated the patient with 3 weekly cycles of atezolizumab 1200 mg plus bevacizumab 15 mg/kg. The patient tolerated the treatment well, and treatment-emergent adverse events included deterioration of hypertension and increased uric protein. After a total of 4 cycles of therapy, abdominal computed tomography findings showed that the metastasis evidently decreased, and a complete response was achieved based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Seventeen days later, the metastasis was dissected. Subsequently, we confirmed that there was no pathological metastatic lesion in the resected lymph node. Our case is the first report of successful application of the radical therapy to lymph node metastasis of HCC via combination therapy with atezolizumab/bevacizumab.