Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

A case of acute liver failure with echovirus infection diagnosed by a multi-virus real-time PCR system

Background: Multi-virus real-time polymerase chain reaction (PCR) system is able to simultaneously detect 163 viruses using a multiplex Taqman real-time PCR system. We present a case of acute liver failure (ALF) of unknown etiology diagnosed with　echovirus 30 infection via multi-virus real-time PCR. Case presentation: A previously healthy 66-year-old man had a persistent fever and developed ALF of unclear etiology. Although viral infection was suspected, serological screening showed no evidence of acute viral infections such as hepatitis A, B, C and E, Epstein-Barr virus, herpes simplex virus, and varicella zoster virus. Multi-virus real-time PCR revealed the presence of enterovirus and echovirus 30 genomes, and reverse transcription-PCR using enterovirus-specific primers confirmed the presence of enterovirus genome in serum samples at the time of admission. Anti-echovirus antibody titers showed an increase in paired sera. In spite of multimodality treatment, the patient died due to multiple organ failure. Histological analysis in autopsy revealed extensive coagulative necrosis of the hepatocytes and immunohistochemical analysis showed the expression of enterovirus antigens in necrotic hepatocytes. Conclusions: We present here a case of echovirus 30 associated with ALF. Multi-virus real-time PCR is useful for detection of virus for patients with ALF of unknown etiology suspected of harboring a viral infection

Preoperative PET-CT is useful for predicting recurrent extrahepatic metastasis of hepatocellular carcinoma after resection

Purpose In recent years, it has been reported that use of 18F-FDG PET-CT can reveal the degree of hepatocellular carcinoma malignancy. We evaluate the ability of a preoperative 18F-FDG PET-CT to predict the recurrence of extrahepatic metastasis of HCC after surgery. Methods We retrospectively examined 67 patients who received 18F-FDG PET-CT prior to curative hepatic resection for HCC between April 2010 and March 2016. Multivariate Cox regression analysis was performed to identify the factors associated with recurrence of extrahepatic metastasis of HCC after surgery. We also evaluated the sensitivity, specifity, positive predictive value, negative predictive value and accuracy of diagnosis of 18F-FDG PET-CT for recurrent extrahepatic metastasis of HCC after surgery. Results The multivariate analysis identified a tumor-to-normal liver standardized uptake value ratio (TNR) ≥ 1.53 (hazard ratio [HR], 0.037; P = 0.003), multiple tumor nodules (HR, 0.121; P = 0.007), and presence of microvascular invasion (HR, 0.094; P = 0.003) as independent predictors of distant metastasis recurrence. A TNR ≥ 1.53 showed a sensitivity of 91.7 %, specificity of 76.4 %, positive predictive value of 45.8 %, negative predictive value of 97.7 %, and accuracy of 79.1 % for diagnosing distant metastasis recurrence of HCC. In a binomial logistic regression analysis of tumor factors associated with a TNR ≥ 1.53, poor tumor differentiation and large tumor size were significant factors. Conclusion 18F-FDG PET-CT and microvascular invasion may be useful for predicting the recurrence of extrahepatic metastasis of HCC after surgery.アクセプト後にアブストラクトに変更あ

Evaluation of Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma Using the Combination of Response Evaluation Criteria in Solid Tumors and Alpha-Fetoprotein

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child–Pugh Score of 5–7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy

Therapeutic Efficacy and Safety of Lenvatinib after Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months–not reached) and 10.5 months (range, 8.2–12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months–not reached) and 4.0 months (range, 2.5–6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child–Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02–0.76, p = 0.02) and intrahepatic tumor occupancy rate p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option