This retrospective multicenter study analyzed 244 patients with unresectable hepatocellular carcinoma treated with lenvatinib (LEN) and atezolizumab + bevacizumab (Atezo + Bev) to examine the ...characteristics, treatment courses, and prognoses. The cases of patients who could achieve HCC downstaging from Barcelona Clinic Liver Cancer (BCLC) stage B or C to A or zero indicated the need for conversion therapy. The patients’ prognoses with and without conversion therapy were compared. Of the 244 patients, 12 (4.9%) underwent conversion therapy, six out of 131 (4.6%) were treated with LEN, and six out of 113 (5.3%) were treated with Atezo + Bev. Eleven patients (91.7%) with a modified albumin bilirubin (mALBI) grade 1 or 2a and BCLC-B stage showed significantly higher rates of transition during conversion therapy (p < 0.05). The patients undergoing conversion therapy had a significantly longer median overall survival rate than those receiving chemotherapy alone (1208 1064–NA vs. 569 466–704 days, p < 0.01). A comparison of the patients who achieved a partial response with and without conversion was evaluated using propensity score matching to reduce the confounding factors, showing a significant survival benefit in the conversion group (1208 1064–NA vs. 665 days, p < 0.01). Among the patients with u-HCC who were treated with LEN and Atezo + Bev, those with mALBI 1 + 2a and BCLC-B were likely to achieve conversion therapy with downstaging.
Background/Aim
A comparison of therapeutic efficacy between atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib treatment given as first‐line therapy for unresectable hepatocellular carcinoma ...(u‐HCC) in regard to progression‐free survival (PFS) overall survival (OS) has not been reported. We aimed to elucidate which of those given as initial treatment for u‐HCC has greater prognostic impact on PFS and OS of affected patients, retrospectively.
Materials/Methods
From 2020 to January 2022, 251 u‐HCC (Child–Pugh A, ECOG PS 0/1, BCLC‐B/C) treated were enrolled (Atez/Bev‐group, n = 194; lenvatinib‐group, n = 57). PFS and OS were analyzed following adjustment based on inverse probability weighting (IPW).
Results
There was a greater number of patients with macro‐vascular invasion in Atez/Bev‐group (22.7% vs. 8.8%, p = 0.022). In lenvatinib‐group, the frequencies of appetite loss (38.6% vs. 19.6%, p = 0.002), hypothyroidism (21.1% vs. 6.7%, p = 0.004), hand foot skin reaction (19.3% vs. 1.0%, p < 0.001), and diarrhea (10.5% vs. 4.6%, p = 0.012) were greater, while that of general fatigue was lower (22.8% vs. 26.3%, p = 0.008). Comparisons of therapeutic best response using modified response evaluation criteria in solid tumors (mRECIST) did not show significant differences between the present groups (Atez/Bev vs. lenvatinib: CR/PR/SD/PD = 6.1%/39.1%/39.1%/15.6% vs. 0%/48.0%/38.0%/14.0%, p = 0.285). In patients of discontinuation of treatments, 48.2% switched to lenvatinib, 10.6% continued beyond PD, 8.2% received another systemic treatment, 5.9% underwent transcatheter arterial chemoembolization (TACE), 3.5% received hepatic arterial infusion chemotherapy (HAIC), and 1.2% underwent surgical resection in Atez/Bev‐group, while 42.2% switched to Atez/Bev, 4.4% continued beyond PD, 4.4% received another systemic treatment, 2.2% nivolumab, 6.7% received TACE, and 2.2% received HAIC in lenvatinib‐group. Following adjustment with inverse probability weighting (IPW), Atez/Bev‐group showed better PFS (0.5−/1−/1.5‐years: 56.6%/31.6%/non‐estimable vs. 48.6%/20.4%/11.2%, p < 0.0001) and OS rates (0.5−/1−/1.5‐years: 89.6%/67.2%/58.1% vs. 77.8%/66.2%/52.7%, p = 0.002).
Conclusion
The present study showed that u‐HCC patients who received Atez/Bev as a first‐line treatment may have a better prognosis than those who received lenvatinib.
This is a first report mentions that a comparison of therapeutic efficacy between atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib treatment given as first‐line therapy for unresectable hepatocellular carcinoma (u‐HCC) in regard to overall survival (OS). Although tumor responses did not show significant differences between both groups, Atez/Bev‐group showed better OS rates following adjustment with IPW (0.5−/1−/1.5‐years: 89.6%/67.2%/58.1% vs. 77.8%/66.2%/52.7%, p = 0.002). Atez/Bev‐group showed better OS as a first‐line treatment as compared to lenvatinib‐group.
Background
Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u‐HCC), changes in hepatic function during therapy have yet to be ...reported.
Aim
This retrospective clinical study aimed to elucidate early responses to Atez/Bev.
Methods
From September 2020 to April 2021, 171 u‐HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin‐bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively.
Results
In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR‐6W/DCR‐6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR‐6W/DCR‐6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post‐progression treatment following lenvatinib (ORR‐6W/DCR‐6W = 7.7%/79.5%), for which no known effective post‐progression treatment has been established. In 111 patients who underwent a 6‐week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (−2.525 ± 0.419 vs −2.323 ± 0.445, p < .001), but then recovered at 6‐weeks (−2.403 ± 0.452) as compared to 3‐weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%).
Conclusion
Atez/Bev might have therapeutic potential not only as first but also later‐line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.
Galectin-9, a soluble β-galactoside-binding animal lectin, evokes apoptosis in various human cancer cell lines. The galectin-9 antitumor effect against hepatocellular carcinoma (HCC) is, however, ...unknown. We investigated whether galectin-9 suppresses HCC growth in vitro and in vivo. We assessed the antitumor effect of galectin-9 on HCC cells by conducting WST-8 assay in vitro and xenograft model analysis in vivo. Galectin-9-induced apoptosis was evaluated by FACS and ELISA in vitro and by TUNEL stain in vivo. Cell cycle alteration was profiled by FACS. Caspases were profiled by colorimetry. MicroRNAs related to the galectin-9 antitumor effects were determined using microarrays, and their antitumor effect was confirmed in a transfection study in vitro. The expression levels of the target proteins of the miRNAs extracted above were analyzed by western blot analysis. To summarize the results, galectin-9 inhibited the growth of the HCC cell lines HLE and Li-7 in vitro and Li-7 in vivo inducing apoptosis. Cell cycle turnover was not arrested in HLE and Li-7 cells in vitro. miR-1246 was similarly extracted both in vitro and in vivo, which sensitized Li-7 cells to apoptosis when transfected into the cells. DYRK1A, a target protein of miR-1246 was downregulated in Li-7 cells. Caspase-9 was upregulated in Li-7 cells in vitro and in vivo. In conclusion, galectin-9 inhibited the growth of HCC cells by apoptosis, but not cell cycle arrest, in vitro and in vivo. miR-1246 mediated signals of galectin-9, possibly through miR-1246-DYRK1A-caspase-9 axis. Galectin-9 might be a candidate agent for HCC chemotherapy.
Aim
We analyzed the association between the modified albumin–bilirubin (mALBI) grade and therapeutic efficacy of atezolizumab plus bevacizumab (Atezo+Bev) for the treatment of unresectable ...hepatocellular carcinoma (u‐HCC).
Methods
In this retrospective observational study, we included 71 u‐HCC patients treated with Atezo+Bev between September 2020 and September 2021. Patients were grouped corresponding to the mALBI grade at the start of treatment (mALBI 1+2a or mALBI 2b+3) and analyzed for therapeutic effect and the transition rate to secondary treatment.
Results
According to the Response Evaluation Criteria in Solid Tumors, the overall response rate was significantly higher for the mALBI 1+2a group, than for the mALBI 2b+3 group, with 26.2% and 3.4%, respectively. The progression‐free survival (PFS) was significantly longer in the mALBI 1+2a group (10.5 months) than in the mALBI 2b+3 group (3.0 months). In the multivariate analysis, an mALBI of 1+2a was found to be an independent factor of PFS. The rate of second‐line treatment with multi‐targeted agents was also significantly higher in the mALBI 1+2a group.
Conclusions
In real‐world practice, Atezo+Bev treatment might have higher therapeutic efficacy in u‐HCC patients with mALBI 1+2a.
Our data suggest that Atezo+Bev treatment has a good anti‐tumor effect on mALBI 1+2a and a reasonable transition rate to the subsequent molecular‐targeted agents treatment.
Aims
To assess the safety, efficacy, and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main ...portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO).
Methods
A total of 61 highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology.
Results
The most frequent grade ≥3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child–Pugh grade (CP)‐A and CP‐B, respectively, and 26.7% and 0% in VP4 HCC patients with CP‐A and CP‐B, respectively. Estimated median progression‐free survival and overall survival were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin‐bilirubin grade (hazard ratio 0.372, 95% CI 0.157–0.887; p = 0.0241) and tumor morphology (hazard ratio 0.322, 95% CI 0.116–0.889; p = 0.0287) were independently associated with progression‐free survival in patients with tm50%LO HCC. In VP4 HCC, median progression‐free survival was worse in CP‐B (57 days) than in CP‐A patients (137 days, p = 0.0462).
Conclusions
Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular‐type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers.
Diaphragmatic hernia (DH) is a defect, which can be congenital or can develop later in life. Moreover, chromosomal and genetic abnormalities, environmental exposures, and nutritional deficiencies may ...be related to the development of congenital DH. In contrast, the risk factors of acquired DH include traumas, such as blunt injuries due to traffic accidents and surgical procedures. We report the case of a 71-year-old man admitted to our gastroenterology department for the treatment of esophageal varices. Four days after the endoscopic treatment, the patient vomited severely and reported severe right upper abdominal pain. He was diagnosed with DH, and surgical fixation was performed. The diaphragmatic injury lesion was located on the estimated needle track of percutaneous radiofrequency ablation, which was performed through the thoracic diaphragm with artificial pleural effusion for hepatocellular carcinoma.
Aim
The incidence of hepatitis C virus (HCV) infection is much higher in hemodialysis patients than that in healthy individuals. The prognosis of hemodialysis patients with HCV infection is poorer ...than that without HCV infection. Therefore, antiviral intervention is pivotal for HCV infection in hemodialysis patients. Recent evaluations of the pangenotypic regimen of glecaprevir/pibrentasvir show that it is highly effective and safe for HCV‐infected hemodialysis patients. However, a few reports showed that the effect of HCV elimination by glecaprevir/pibrentasvir improved liver dysfunction or anemia. The aim of the present study was to determine clinical outcomes after HCV elimination using the glecaprevir/pibrentasvir regimen in HCV‐infected hemodialysis patients.
Methods
This study was a retrospective, six‐center study conducted in Japan, in which 24 hemodialysis patients with HCV genotype 1–2 treated with glecaprevir/pibrentasvir were recruited. Blood examinations were performed at end of treatment (EOT), and at 3, 6, and 12 months post‐treatment during the 12‐month follow‐up period.
Results
The overall sustained virologic response rate was 100% (24/24). During the DAA treatment period, adverse events were observed in 20.8% of patients (5/24), and pruritus was the most frequently observed in 12.5% (3/24). Interestingly, we observed an improved control of anemia after EOT with a significant increase in hemoglobin levels. In addition, total bilirubin was diminished, and platelet counts and albumin, total cholesterol, and alpha‐fetoprotein levels remained unchanged after EOT in hemodialysis patients. Furthermore, erythropoietin concentration was not increased after EOT.
Conclusions
HCV elimination using glecaprevir/pibrentasvir treatment might be a major breakthrough for the control of anemia in hemodialysis patients.
Background and Aim
Chronic liver diseases progress from chronic inflammation to fibrosis to tumorigenesis. Galectin‐9, a β‐galactoside‐specific animal lectin, is indicated to contribute to all three ...steps of progression. The aim of this study was to determine which of the three steps was most dominant in elevating the serum galectin‐9 concentration and to test the possibility of galectin‐9 as a serum biomarker.
Methods
Japanese patients with chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), non‐alcoholic fatty liver disease, or alcoholic liver disease who provided informed consent were enrolled in this study. Serum galectin‐9 levels were measured using a sandwich ELISA. Multiple regression analyses were performed using ezr to identify factors that determined serum galectin‐9 concentration.
Results
One hundred one patients with 50 of chronic hepatitis and 51 of liver cirrhosis were enrolled; the cohort included 45 cases of hepatitis C virus infection, 13 cases of hepatitis B virus infection, and 46 cases with HCC‐related complications. The median serum galectin‐9 concentration was 77.54 pg/mL (interquartile range: 18.89–241.9 pg/mL). Multiple linear regression analyses proved Fibrosis‐4 index and aspartate aminotransferase to platelet ratio index, indexes of liver fibrosis, were able to predict the serum galectin‐9 levels with statistical significance. A multiple logistic regression analysis determined 10 pg/mL increase in the serum galectin‐9 concentration presented an odds ratio of 3.90 for liver fibrosis progression.
Conclusions
The serum galectin‐9 concentration represents a potential biomarker of liver fibrosis in patients with chronic liver diseases, regardless of chronic inflammation or the presence of HCC complications. Furthermore, higher serum galectin‐9 levels are a predictor for liver fibrosis progression.
Background We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Methods Forty-five patients ...with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Results Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy ( n = 7) and devascularization for esophagogastric varices ( n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values ( P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels ( P = .03), and increased prothrombin activity ( P = 003) and decreased Child-Pugh scores ( P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. Conclusion LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis.
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