Display omitted
•Recurrence is frequent within 2 years of surgical resection of hepatocellular carcinoma.•In this large collaboration, we identify readily available, clinical parameters which ...influence early recurrence.•A simple and extensively validated statistical model for estimating early recurrence risk using an online calculator.•This facility will enhance patient counselling and will help in design of adjuvant clinical trials.
Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30–50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection.
A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application.
Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort – low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included ‘microvascular invasion’.
Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials.
The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.
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.
Background
Hepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with ...chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC.
Methods
1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC.
Results
85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10–4.14,
P
= 0.025). HBcrAg above 2.9 log
10
U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (
P
= 0.024 by Kaplan–Meier analysis), and possibly in cirrhotic patients (
P
= 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups.
Conclusion
Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.
Background
Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving ...hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis.
Methods
The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction.
Results
The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (
p
= 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (
p
= 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups.
Conclusions
The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
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 aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma ...(HCC), focusing on how their impact changes over time after diagnosis. Alpha‐fetoprotein (AFP), des‐gamma‐carboxy prothrombin (DCP), albumin‐bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB‐4 index were measured at the time of initial non‐recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time‐dependent receiver‐operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB‐4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time‐dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB‐4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time‐dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis.
Although tumor progression, liver function, and the degree of liver fibrosis significantly predict the survivals of patients with hepatocellular carcinoma, respectively, the impacts of these factors on patient prognosis are different over time.
We sought to determine whether hypointense hepatocellular nodules observed in the hepatobiliary phase of MRI enhanced with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadoxetate ...disodium) progress to hypervascular hepatocellular carcinoma.
Gadoxetate disodium-enhanced MRI was repeated for 30 patients with 49 nodules determined to be hypointense in the hepatobiliary phase but nonenhancing in the arterial phase of dynamic MRI. The correlation between characteristics of hypointense nodules with slightly or markedly low signal intensity relative to surrounding liver parenchyma and their progression to hypervascular hepatocellular carcinoma was analyzed in cirrhotic livers. All patients underwent angiography-assisted CT before MRI. The rate of progression to classic hepatocellular carcinoma was calculated by the Kaplan-Meier method.
The overall 6- and 12-month cumulative incidences of vascularization were 27.6% and 43.5%. The 6- and 12-month cumulative incidences of vascularized nodules with a maximum diameter 15 mm or greater were 43.3% and 77.3% and a maximum diameter less than 15 mm were 16.9% and 16.9%. The difference between these incidences was significant (p = 0.0147).
Hypointense nodules with a maximum diameter of at least 15 mm often become hypervascular. Therefore, patients with hypointense nodules characterized by a maximum diameter of 15 mm or greater should be observed carefully because of the high incidence of vascularization.
OBJECTIVE:We reviewed nationwide follow-up data to determine outcomes of different treatments for early-stage hepatocellular carcinoma (HCC) in elderly patients.
SUMMARY BACKGROUND DATA:Outcomes of ...early-stage HCC treatments in elderly patients have not been prospectively compared.
METHODS:We included 6490 HCC patients, aged ≥75 years at treatment, who underwent curative hepatic resection (HR, n = 2020), radiofrequency ablation (RFA, n = 1888), microwave ablation (MWA, n = 193), or transcatheter arterial chemoembolization (TACE, n = 2389), and compared their characteristics and survival. We used matching propensity score analysis (PSA) between the HR and RFA subgroups with tumors ≤3 cm to overcome baseline bias.
RESULTS:The HR group had significantly longer recurrence-free survival (RFS) than the RFA, MWA, and TACE groups RFA vs HR—hazard ratio1.22, 95% confidence interval (CI)1.09–1.37, P < 0.001; MWA vs HR—hazard ratio1.51, 95% CI1.22–1.88, P < 0.001; TACE vs HR—hazard ratio2.70, 95% CI2.44–2.99, P < 0.001). HR and RFA patients had significantly longer overall survival (OS) than the TACE group (RFA vs HR—hazard ratio1.01, 95% CI0.87–1.17, P = 0.919, TACE vs HR—hazard ratio2.11, 95% CI1.86–2.40, P < 0.001). PSA successfully matched HR and RFA patients from with primary HCC tumors ≤3.0 cm and similar liver function and tumor characteristics; and showed significantly longer RFS (hazard ratio1.64, 95% CI1.29–2.10, P < 0.001) and OS (hazard ratio1.57, 95% CI1.12–2.20, P = 0.009) for HR than for RFA (including subgroup analyses). In Cox proportional hazard analysis, HR offered better prognosis than RFA.
CONCLUSIONS:HR decreases recurrence risk and improves OS in patients aged ≥75 years with primary HCC tumors ≤3.0 cm.
Hepatocellular carcinoma (HCC) is responsible for approximately 600 000–700 000 deaths worldwide. It is highly prevalent in the Asia–Pacific region and Africa, and is increasing in Western countries. ...The evidence‐based guideline for HCC in Japan was published in 2005 and revised in 2009. Apart from this guideline, a consensus‐based practice manual proposed by the HCC expert panel of the Japan Society of Hepatology (JSH), which reflects widely accepted daily practice in Japan, was published in 2007. At the occasion of the 45th Annual meeting of the JSH in Kobe 4–5 June 2009, a consensus meeting of HCC was held. Consensus statements were createdbased on 67% agreement of 200 expert members.This article describes the up‐to‐date consensus statements which largely reflect the real world HCC practice in Japan. We believe readers of this article will gain the newest knowledge and deep insight on the management of HCC proposed by consensus of the HCC expert members of JSH.
PDF
