The predictors of hepatitis B virus (HBV) relapse and HBsAg loss after cessation of nucleos(t)ide analogues (NA) in HBeAg-negative patients with end-of-treatment HBsAg ≤ 200 IU/mL remains unclear. ...The study recruited 119 chronic hepatitis B (CHB) patients who achieved end-of-treatment HBsAg ≤ 200 IU/mL, were treated with lamivudine (n = 34) and entecavir (n = 85). The 5-year rates of post-treatment virological relapse, clinical relapse, and HBsAg loss at 60 months were 39.4%, 27.6%, and 45.9%, respectively. Cox regression analysis revealed that HBV DNA at entry and end-of-treatment HBsAg levels were independent predictors of virolgical and clinical relapse. HBV genotype C and end-of-treatment HBsAg were independent factors of HBsAg loss. Patients with a combination of end-of-treatment HBsAg < 50 IU/mL and HBV DNA < 2 × 10
IU/mL at entry experienced the lowest virological and clinical relapse rates (5% and 0% at 60 months, respectively). In contract, patients with a combination of end-of-treatment HBsAg ≥ 50 IU/mL and HBV DNA ≥ 2 × 10
IU/mL at entry experienced high virological and clinical relapse (80.7% and 71.5% at 60 months, respectively). No patients experienced hepatic decompensation when clinical relapse occurred after timely retreatment. A combination of HBV DNA levels at entry and end-of-treatment HBsAg levels was useful for predicting the post-treatment HBV relapse in HBeAg-negative patients with HBsAg ≤ 200 IU/mL.
This study investigated the ability of hepatitis B core‐related antigen (HBcrAg) to predict hepatitis B virus (HBV) relapse in HBeAg‐negative patients after cessation of entecavir therapy. A total of ...301 HBeAg‐negative patients without cirrhosis who had stopped entecavir therapy for at least 12 months were recruited. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. The five‐year cumulative rates of virological relapse, clinical relapse and HBsAg loss were 71.6%, 57.3% and 18.7%, respectively. Serum HBsAg at end of treatment (EOT) was an independent predictor of virological relapse, clinical relapse and HBsAg loss; an EOT HBsAg of 150 IU/ml was the optimal cut‐off value. The 5‐year virological relapse rates for patients with <150 and ≥150 IU/ml HBsAg at EOT were 43.3% and 82.2% (p < 0.001), clinical relapse rates were 32.3% and 66.3% (p < 0.001), and HBsAg loss rates were 46.1% and 5.2% (p < 0.001), respectively. A baseline HBcrAg of 4 IU/ml was the optimal cut‐off value for predicting HBV relapse. Among patients with an EOT HBsAg <150 IU/ml, the five‐year virological relapse rates for patients with baseline HBcrAg levels ≤4 and >4 log U/ml were 27.9% and 59.1% (p = 0.006) and the clinical relapse rates were 18% and 48.1% (p = 0.014), respectively. EOT HBcrAg was not a significant predictor of virological or clinical relapse after cessation of entecavir. In conclusion, the combination of an EOT HBsAg of 150 IU/ml and baseline HBcrAg of 4 log U/ml can effectively predict the risk of HBV relapse after stopping entecavir therapy.
Background
Hepatocellular carcinoma (HCC) patients still have risk for very late recurrence after curative resection. This study assesses prognostic factors in HCC patients with recurrence-free ...survival (RFS) for 5 years after primary resection.
Methods
We enrolled 383 HCC patients who received primary tumor resection and achieved more than 5 years without recurrence after resection between January 2001 and April 2013. Predictive factors, including albumin-bilirubin (ALBI) grade, for RFS and overall survival (OS) were analyzed.
Results
After a median follow-up of 103 months, 57 patients (14.9%) had recurrent HCC, and 14 (3.7%) died. Independent predictors for HCC recurrence were male sex (
p
= 0.035), pre-operative liver cirrhosis (LC) (
p
= 0.025), serum creatinine > 1.5 mg/dL (
p
= 0.045), post-operative 5th-year alpha-fetoprotein (AFP) > 15 ng/ml (
p
< 0.001), LC (
p
= 0.004), and ALBI grades 2 and 3 (
p
< 0.001). I ndependent risk factors for poor survival were age >70 years (
p
= 0.002), post-operative 5th-year AFP > 15 ng/ml (
p
= 0.003), and ALBI grades 2 and 3 (
p
= 0.002). Patients whose deteriorated ALBI grades 5 years after resection had adverse RFS outcomes compared to those with constant (
p
= 0.056) and improved ALBI grades (
p
= 0.008). In subgroup analysis, patients with post-operative 5th-year ALBI grades 2 and 3 had significantly poorer RFS and OS (both
p
< 0.001) than those with grade 1 among patients with low post-operative 5th-year AFP (<15 ng/mL).
Conclusion
In HCC patients without recurrence for 5 years after curative resection, post-operative 5th-year ALBI grade is useful for predicting outcomes, even with low AFP during follow-up.
Background & Aims To compare the survival between surgical resection (SR) and radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) ...very early/early stage. Methods Between 2002 and 2009, patients with newly diagnosed BCLC very early/early stage HCC who received SR or RFA were enrolled. Medical records were reviewed. The cumulative overall survival (OS) and disease-free survival (DFS) were compared. Results A total of 605 patients, including 143 very early (SR: 52; RFA: 91) and 462 early stages (SR: 208; RFA: 254) were enrolled. For very early stage, the 3- and 5-year OS rates were 98% and 91.5% for SR, and 80.3% and 72% for RFA, respectively ( p = 0.073). The 3- and 5-year DFS rates were 62.1% and 40.7% for SR, and 39.8% and 29.3% for RFA, respectively ( p = 0.006). Either multiple adjustment by Cox model or match analysis based on propensity score showed no significant difference in OS between the two groups. For early stage, the 3- and 5-year OS rates were 87.8% and 77.2% for SR, and 73.5% and 57.4% for RFA, respectively ( p = 0.001). The 3- and 5-year DFS rates were 59.9% and 50.8% for SR, and 28.3% and 14.1% for RFA, respectively ( p <0.001). After adjusting covariates, there was no significant difference in OS between the two groups. However, SR was superior to RFA in DFS. Conclusions For HCC patients in BCLC very early/early stage, there was no significant difference in OS between SR and RFA. However, SR yielded better DFS than RFA.
Background The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to ...reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC). Methods We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan-Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child-Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1-2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment. Conclusion Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice. Keywords: Nivolumab, Low dose, Hepatocellular carcinoma, Immunotherapy
Transient elastography and fibrosis-4 index (FIB-4) have been proposed to access hepatic fibrosis and steatosis for patients with chronic liver disease. This study was to determine the changes of ...liver stiffness (LS), controlled attenuation parameter (CAP) value and FIB-4 and their associated factors for chronic hepatitis C (CHC) patients who underwent direct-acting antivirals (DAAs).
Consecutive patients with CHC in advanced fibrosis or compensated cirrhosis undergoing paritaprevir/ritonavir/ombitasvir plus dasabuvir therapy and with LS and CAP before and 12 weeks after treatment were enrolled. The demographics, clinical characteristics and treatment outcomes were reviewed. The changes of LS, FIB-4, CAP and their associated factors were analyzed.
A total of 213 patients (mean age: 63.7 years) with complete recommended treatment were enrolled. All patients achieved sustained virological response at 12 weeks (SVR12) of follow-up. The mean values of LS, CAP and FIB-4 index before treatment were 18.5kPa, 283dB/m and 5.05 respectively. While there was no significant change in CAP, LS and FIB-4 decreased significantly at the time of SVR12 (p<0.001). Compared with follow-up period, LS and FIB-4 decreased rapidly during DDAs. Multivariate analysis showed that higher baseline LS and FIB-4 were associated with greater reductions at the time of SVR12.
For CHC patients in advanced fibrosis or compensated cirrhosis, DAAs improved LS and FIB-4 index at SVR12. Higher baseline LS and FIB-4 contributed to greater reductions. However, there was no significant change in CAP value.
Background and Aim
The Albumin‐Bilirubin (ALBI) grade is a new index to assess objectively liver function and prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to elucidate ...the application of ALBI grade in baseline and sorafenib‐end in advanced HCC patients who received sorafenib.
Methods
A total of 415 consecutive advanced HCC patients in Child–Pugh A received sorafenib in our hospital. Sorafenib was terminated when radiologic tumor progression or clinical liver function deterioration (LD) occurred in the reassessment bimonthly. Patients who failed with sorafenib monotherapy were retrospectively analyzed.
Results
A total of 260 (62.6%) patients were enrolled, including 98 (37.7%) ALBI grade I and 162 (62.3%) grade II in baseline. More patients in ALBI grade II stopped sorafenib because of LD than in grade I (33.3% vs 14.3%, P < 0.001). Those who in baseline ALBI grade I had a superior overall survival than in grade II (8.5 months vs 4.4 months, P = 0.003). Cox regression analysis confirmed that baseline ALBI grade II (P < 0.001) and ALBI grade increase during treatment (P < 0.001) strongly contributed to the mortality of HCC patients who received sorafenib. After sorafenib failure, those with post‐sorafenib treatment had a better post‐sorafenib survival than those without (9.3 vs 1.6 months, P < 0.001). Logistic regression analysis indicated that sorafenib‐end ALBI grade and LD occurrence were the only two predictors of post‐sorafenib treatment after sorafenib failure.
Conclusions
In clinical practice, we firstly demonstrated that not only ALBI grade in baseline but also ALBI grade change during treatment could predict the prognosis of advanced HCC patients who received sorafenib.
This study investigated the incidence and predictors of hepatitis B virus (HBV) relapse in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who discontinued entecavir (ETV) or ...tenofovir disoproxil fumarate (TDF).
A total of 205 and 111 HBeAg-positive patients without cirrhosis who had stopped ETV or TDF treatment, respectively, for at least 6 months were recruited.
In the entire cohort, patients with HBeAg seroconversion during treatment, and propensity score-matched patients, those who discontinued TDF had significantly higher rates of virological and clinical relapse than patients who discontinued ETV therapy. Multivariate analysis identified that TDF was independently associated with virological and clinical relapse in the entire cohort and subgroup analysis. Patients with HBeAg loss without anti-HBe antibody formation during treatment had significantly higher rates of off-therapy HBV relapse and HBeAg seroreversion than patients with HBeAg seroconversion during treatment. The hepatitis B core-related antigen (HBcrAg) level at end of treatment (EOT) was independently associated with HBV relapse and HBeAg seroreversion in all patients and patients with HBeAg seroconversion during treatment.
TDF therapy, HBeAg loss without seroconversion during treatment, and higher HBcrAg levels at EOT are significant predictors of HBV relapse in HBeAg-positive patients who discontinued ETV or TDF.
Background Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in ...patients with advanced hepatocellular carcinoma (HCC) in real-world practice. Methods We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). Results In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1-2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. Conclusion The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice. Keywords: Hepatocellular carcinoma, Pembrolizumab, Nivolumab, Immunotherapy
Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and ...DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age‐ and sex‐matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow‐up. A panel of ten cancer‐associated miRNAs was analyzed by quantitative real‐time reverse‐transcription polymerase chain reaction. Serum levels of miR‐16, miR‐122, miR‐221, let‐7b and miR‐15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR‐122, miR‐let‐7b and miR‐15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α‐fetoprotein (AFP) and miR‐122 as well as let‐7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let‐7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR‐122 and let‐7b, which are upregulated in the serum of early‐HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.
What's new?
Due to late detection, the prognosis for hepatocellular carcinoma (HCC) is generally dismal. HCC‐specific biomarkers are thus urgently needed, especially in areas where hepatitis B is endemic. In this study, the authors found that serum levels of certain microRNAs (miRNAs) are significantly higher in patients with early HCC, compared to those with dysplastic nodules of the liver. These specific miRNAs may therefore provide a useful screening tool for early detection of HCC, which could greatly improve treatment outcomes.
PDF
