Background
The effects of direct-acting antivirals (DAAs) on survival and recurrence rates after curative hepatocellular carcinoma (HCC) treatment in patients with hepatitis C virus (HCV) infection ...remain controversial.
Methods
This retrospective, multicenter study involved Child–Pugh class A patients within the Milan criteria who had a first diagnosis of HCC and survived 6 months or longer after undergoing hepatectomy or radiofrequency ablation (RFA). The DAA-treated group (DAA group) included 56 patients, and the DAA-untreated group (untreated group) included 261 patients. The study was conducted using the propensity score-matched (1:2) DAA group and untreated group, 56 and 112 patients, respectively.
Results
The survival rate at 48 months in the DAA group and the untreated group was 91.0% and 68.7%, respectively, showing significantly better survival in the DAA group (HR: 0.33; 95% CI 0.13–0.84;
p
= 0.021). The recurrence rate at 48 months was 36.7% and 66.7%, respectively, showing a significantly lower recurrence rate in the DAA group (HR, 0.46; 95% CI 0.27–0.77;
p
= 0.003). The median albumin–bilirubin (ALBI) score at 3 years post-HCC treatment was − 2.84 in the DAA group and − 2.34 in the untreated group. The ALBI score showed a significant improvement from baseline to 3 years post-HCC treatment (
p
= 0.001), whereas that in the untreated group showed a significant decline (
p
= 0.040).
Conclusions
DAAs after HCC treatment prevents deterioration of hepatic functional reserve and significantly improves both recurrence and survival rates.
Aim
Lenvatinib (LEN) has recently become available as a first‐line tyrosine‐kinase inhibitor (TKI) for unresectable hepatocellular carcinoma (u‐HCC). In patients who showed intolerability or failure ...in other TKI treatments, alternative treatment options are needed. This retrospective study evaluated the therapeutic potential of LEN in clinical practice.
Methods
We enrolled 57 u‐HCC patients treated with LEN from March to June 2018. Lenvatinib was given orally to patients weighing <60 kg at 8 mg/day and at 12 mg/day to those ≥60 kg. Following the exclusion of patients whose initial LEN dose was reduced, 49 patients were evaluated in regard to their characteristics and early therapeutic response using modified Response Evaluation Criteria in Solid Tumors for findings of follow‐up computed tomography (CT)/magnetic resonance imaging (MRI) examinations at 4 weeks after introducing LEN.
Results
The average patient age was 72.4 ± 9.3 years and 38 (77.6%) were men. The LEN dose was 8 and 12 mg in 32 and 17 patients, respectively. Twenty‐nine (59.2%) had history of treatment with sorafenib and six of them (20.7%) with regorafenib. Of the 49 patients, 27 were evaluated using findings obtained by enhanced CT/MRI at 4 weeks after introducing LEN. Partial response was shown in 11, stable disease in 12, and progressive disease in four (overall response rate ORR, 40.7%; disease control rate DCR, 85.2%). The ORR and DCR of TKI‐naïve patients (n = 8) were 50.0% and 87.5%, respectively, whereas those of TKI‐experienced patients (n = 19) were 36.8% and 84.2%, respectively (P = 0.675 and P = 1.00, respectively).
Conclusion
Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments.
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with ...consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on ...lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.
In the 2010 version of the Japan Society of Hepatology (JSH) consensus-based treatment algorithm for the management of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) ...failure/refractoriness was defined assuming the use of superselective lipiodol TACE, which has been widely used worldwide and particularly in Japan, and areas with lipiodol deposition were considered to be necrotic. However, this concept is not well accepted internationally. Furthermore, following the approval of microspheres, an embolic material that does not use lipiodol, in February 2014 in Japan, the phrase 'lipiodol deposition' needed to be changed to 'necrotic lesion or viable lesion'. Accordingly, the respective section in the JSH guidelines was revised to define TACE failure as an insufficient response after ≥2 consecutive TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, even after chemotherapeutic agents have been changed and/or the feeding artery has been reanalyzed. In addition, the appearance of a higher number of lesions in the liver than that recorded at the previous TACE procedure (other than the nodule being treated) was added to the definition of TACE failure/refractoriness. Following the discussion of other issues concerning the continuous elevation of tumor markers, vascular invasion, and extrahepatic spread, descriptions similar to those in the previous version were approved. The revision of these TACE failure definitions was approved by over 85% of HCC experts.
This contingency guide was formulated on the premise that delivering standard treatment for hepatocellular carcinoma (HCC) has come under strain due to the coronavirus (COVID‐19) pandemic. Measures ...required are likely to vary largely across regions and individual institutions, depending on the level of the strain imposed by the pandemic (e.g., number of inpatients infected with COVID‐19 and the availability of resources, including personal protective equipment and inpatient beds). In addition, models suggest that the second and third waves of COVID‐19 will occur before effective vaccines and medicines become widely available in Japan (expected time, 2–3 years). This guide should serve as a good reference for best practices in the management of HCC, which is in light of the possible risk of impending collapse of the healthcare system due to a surge in COVID‐19 infections.
This study investigated the impact of baseline liver function according to the Child-Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular ...carcinoma treated with lenvatinib.
A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child-Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child-Pugh score 5 and ALBI grade 1 (group 1), (2) Child-Pugh score 5 and ALBI grade 2 (group 2), (3) Child-Pugh score 6 (group 3), and (4) Child-Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events.
Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (
< 0.05 and
< 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (
< 0.05 and
< 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (
< 0.01).
Patients with Child-Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment.
Background/Aim: Recently, albumin-bilirubin (ALBI) scoring/grading, consisting of only albumin and total bilirubin, has been proposed. We examined the efficacy of this grading system for determining ...hepatic function in patients with hepatocellular carcinoma (HCC). Methods/Materials: The prognoses of 46,681 HCC patients based on results obtained from a nationwide survey conducted in Japan from 2001 to 2007 were evaluated using (1) Japan Integrated Staging (JIS), consisting of Child-Pugh classification and TNM staging (TNM), (2) modified JIS (m-JIS), consisting of liver damage grading and TNM, and (3) ALBI-TNM (ALBI-T), consisting of ALBI grading and TNM, and the results were compared. A subanalysis was also performed to define a cutoff value for ALBI scores for a more detailed stratification of hepatic function. Results: ALBI-T, JIS, and m-JIS each showed good capacity for the stratification of prognoses. Although the Akaike information criterion for ALBI-T was nearly equal to that for JIS and m-JIS, the Kaplan-Meier curves and median survival times obtained with ALBI-T were always superior to the corresponding scores. When the indocyanine green retention test (<30%) was used as an additional cutoff value for ALBI score (-2.270, area under the curve 0.828) to divide ALBI grade into 4 levels (modified ALBI mALBI grade), mALBI grade was able to stratify the prognosis of patients at any TNM stage in order of grade. Modified ALBI-T (mALBI-T), using mALBI grading and TNM, produced a more detailed stratification for prognosis. Conclusion: The predictive value for prognosis of ALBI-T was found to be equal to that of JIS and m-JIS. In addition, mALBI grading and mALBI-T, as proposed in the present study, might provide a more detailed assessment of the hepatic function and prognosis of HCC patients.
The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study ...Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness.
Background/Aim: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging ...of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. Materials/Methods: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. Results: In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. Conclusion: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.
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