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.
Aim
Direct‐acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of ...sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real‐world clinical practice.
Methods
A prospective, multicenter study of 12‐week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post‐treatment.
Results
The cohort included 8 patients with Child–Pugh class A, 56 with B, and 22 with C. The proportion of Child–Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post‐treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child–Pugh class B and C, univariate analysis identified low total bilirubin, Child–Pugh score, Child–Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child–Pugh class A. The optimal cut‐off value of the factors for predicting improvement to Child–Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child–Pugh score, and −1.88 for ALBI score.
Conclusion
Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post‐treatment and maintained the stable effects until 48 weeks post‐treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child–Pugh class A at 48 weeks post‐treatment.
Background
The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese ...patients chronically infected with hepatitis C virus (HCV) genotype 1.
Methods
The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics.
Results
Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment.
Conclusions
The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.
AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors ...in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient（HVPG） value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65（range, 40-82） years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10-6) and-1.3 kg(P = 1.83 × 10-5), respectively. The median HVPG value was 240（range, 105-580） mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H2 O in predicting treatment response. The response rate was 87.5%（7/8） in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%（2/16） in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10-4). We compared each characteristics factors between responders and non-responders. As a result, HVPG（P = 0.045） and serum hyaluronic acid（P = 0.017） were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.
Aim
From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with ...impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis.
Methods
A retrospective, multicenter study evaluated the outcome of 12‐week ombitasvir (non‐structural protein NS5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir combination therapy for dialysis patients. The primary end‐point was sustained virologic response 12 weeks after therapy (SVR12).
Results
The subjects were 31 patients with a median age of 64 years (range, 49–85 years), including 10 cirrhotic patients. All of the 31 patients had an estimated glomerular filtration rate level <15 mL/min/1.73 m2, defined as end‐stage renal disease (ESRD). Pre‐existing resistance‐associated substitutions at position L31 and Y93 of the NS5A region were detected in 0% and 3.6% (1/28), respectively. The rates of rapid virologic response, end‐of‐treatment response, and SVR12 were 93.5% (29/31), 100% (31/31), and 96.8% (30/31), respectively. The incidence of adverse events was 35.5% (11/31). Of the 11 patients, one discontinued the treatment due to erythema multiforme and thereafter relapsed. The most frequent adverse event was pruritus (6.5%; 2/31).
Conclusions
The present study suggests that ombitasvir/paritaprevir/ritonavir combination therapy is effective and safe for genotype 1b chronic hepatitis C patients undergoing dialysis due to ESRD.
Aim
Serum Mac‐2 binding protein (M2BP) and Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) are used to estimate the liver fibrosis stage in chronic liver diseases. However, ...few head‐to‐head studies have been carried out to compare the two biomarkers in non‐alcoholic fatty liver disease (NAFLD).
Methods
Serum M2BP and WFA+‐M2BP levels were compared against clinical characteristics and liver histological manifestations in the same samples collected from 213 biopsy‐proven NAFLD patients.
Results
Median levels (range) of M2BP and WFA+‐M2BP were 1.58 (0.70–7.75) pg/mL and 0.85 (0.22–11.32) cut‐off index (COI), respectively. Fibrosis stages 1, 2, 3, and 4 were determined in 136, 37, 17, and 23 patients, respectively. Median levels of both biomarkers increased stepwise with fibrosis progression. The M2BP and WFA+‐M2BP levels showed a significant positive correlation (r = 0.643, P = 2.91 × 10−26), but a marked discrepancy between both biomarkers was noted in five stage 4 and three stage 1 patients, who had high WFA+‐M2BP but relatively low M2BP levels. Most of these outliers had findings suggestive of more advanced fibrosis. For diagnosing any fibrosis severity, WFA+‐M2BP had greater area under the receiver operating characteristic curve (AUC) and predictive accuracy than M2BP. Among eight fibrosis markers/indices, WFA+‐M2BP yielded the second highest AUC (0.832) and the highest predictive accuracy (82.2%) to diagnose cirrhosis. In addition, WFA+‐M2BP showed the second highest predictive accuracy to diagnose severe fibrosis (78.4%) and significant fibrosis (76.1%).
Conclusion
This head‐to‐head comparison suggests that WFA+‐M2BP is superior to M2BP for distinguishing liver fibrosis stages in NAFLD patients. A marked discrepancy between the two biomarkers may be indicative of advanced NAFLD (UMIN000023286).
Aim
Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after ...regorafenib failure.
Methods
From June 2017 to October 2020, 63 patients with Child–Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R‐L group, n = 47) and those who did not receive lenvatinib after regorafenib (non‐R‐L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting.
Results
Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R‐L and non‐R‐L groups, whereas the albumin‐bilirubin score, Child–Pugh class, and tumor burden were not. Progression‐free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R‐L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin‐bilirubin grade 2b (score >−2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment.
Conclusion
These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.
Aim
Predicting the survival of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/bev) remains a challenge. This study aims to validate the modified ...albumin–bilirubin grade and α-fetoprotein score (mALF score).
Methods
This retrospective, multicenter study included 426 HCC patients receiving Atez/Bev. Each patient was randomized 3:2 to a training set (
n
= 255) and a validation set (
n
= 171). We investigated prognostic factors in the training set and developed an easily applicable mALF score, which was evaluated in the validation set.
Results
We built the mALF score using baseline mALBI grade 2b or 3 (HR 2.36, 95% CI 1.37–4.05,
p
= 0.002) and α-fetoprotein ≥ 100 ng/ml (HR 2.61, 95% CI 1.49–4.55,
p
< 0.001), which were identified as unfavorable prognostic factors in a multivariate analysis. The 1-year OS rates were 82.7% (95% CI 68.9–90.8) in patients who meet neither of the criteria (mALF 0 points,
n
= 101), 61.7% (95% CI 44.5–74.9) in patients who meet either of the two criteria (mALF 1 point,
n
= 109), and 24.6% (95% CI 9.0–44.3) in patients who meet both criteria (mALF 2 points, n = 45); the difference was statistically significant (
p
< 0.001). The median PFS in patients with mALF 0, 1, and 2 points was 9.5 months (95% CI 4.3-NA), 6.6 months (95% CI 6.0–8.0), and 3.8 months (95% CI 3.0–5.2), respectively, which amounted to a significant difference (
p
< 0.001). These results were confirmed in the validation set (1-year OS rates, 0/1/2 points = 94.2%/62.1%/46.3%,
p
< 0.001; median PFS, 0/1/2 points = 9.3/6.7/4.7 months,
p
= 0.018).
Conclusion
The mALF score can reliably predict the prognosis of HCC patients receiving Atez/Bev.
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