Pretreatment Alpha-fetoprotein Research Articles

Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study.

In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.

The number of hepatocellular carcinoma foci as predictor of poor response to tumor-directed therapies in patients awaiting liver transplantation: a prospective cohort study.

Tumor-directed therapies (TDTs) are a constitutive part of hepatocellular carcinoma (HCC) treatment in patients awaiting liver transplantation (LT). While most patients benefit from TDTs as a bridge to LT, some patients drop out from the waiting list due to tumor progression. The study aimed to determine the risk factors for poor treatment outcome following TDTs among patients with HCC awaiting LT. A total of 123 patients with HCC were evaluated with 92 patients meeting Milan Criteria enrolled in the prospective cohort study. Tumor response was evaluated using the modified Response Evaluation Criteria for Solid Tumors for HCC 1 month after the procedure. The risk factors for progressive disease (PD) and dropout were evaluated. After TDT, 55 patients (59.8%) achieved complete or partial response (44.6% and 15.2% respectively), 17 patients (18.5%) had stable disease, and 20 patients (21.7%) were assessed as PD. Multivariate analysis revealed a significant and independent association between the number of HCC foci and PD ( P = 0.03, OR = 2.68). There was no statistically significant association between treatment response and demographics, MELDNa score, pre-and post-treatment alpha-fetoprotein (AFP), cumulative tumor burden the largest tumor size, or TDT modality. PD was the major cause of dropout in our cohort. Pre-treatment AFP levels ≥200 ng/ml had a strong association with dropout after TDTs ( P = 0.0005). This study demonstrated the presence of multifocal HCC is the sole prognostic factor for PD following TDTs in HCC patients awaiting LT. We recommend prioritizing patients with multifocal HCC within Milan criteria by exception points for LT to improve the dropout rate.

Significance of pretreatment alpha-fetoprotein in patients with compensated severe fibrosis after hepatitis C viral eradication.

We aimed to investigate the factors associated with improvement of liver functional reserve after sustained virological response using interferon-free, direct-acting antiviral combination treatment in patients with compensated, severe fibrosis. Between September 2014 and April 2020, 492 patients received direct-acting antiviral combination treatment in our hospital. Among them, 173 patients who had severe fibrosis based on a fibrosis-4 index ≥3.25, showed sustained virological response after treatment. We investigated the dynamic change in albumin-bilirubin score and the baseline factors associated with its improvement, 48 weeks after treatment. The baseline significant factors associated with albumin-bilirubin≦ -0.5 were lower albumin (HR: 15.625, 95% CI: 4.273-58.824, P < .001), higher hepatitis C virus RNA (HR: 4.995, 95% CI: 1.882-13.260, P=.001), and higher alpha-fetoprotein (HR: 1.033, 95% CI: 1.011-1.055, P=.003). Patients with alpha-fetoprotein ≧10ng/mL showed significant improvement of albumin-bilirubin score from baseline to 48 weeks after treatment compared to those with alpha-fetoprotein <10ng/mL (P < .001). Baseline serum alpha-fetoprotein might be a predictive factor for improvement of liver function after sustained virological response in patients with severe fibrosis.

Long-term outcomes of endoscopic ultrasound-guided laser ablation for liver tumors in the caudate lobe: 5 years of experience

Objectives Liver tumor in the caudate lobe is challenging to treat, partly due to its deep location. Endoscopic ultrasound-guided laser ablation (EUS-LA) is a new attractive option for tumors in high-risk or difficult-to-reach locations. This prospective study investigated the long-term efficacy of EUS-LA for tumors in the caudate lobe, and factors that predict outcomes. Methods From June 2016 to July 2021, twenty consecutive patients (aged 56.95 ± 10.06 years) with 25 caudate lobe tumors (15.64 ± 6.37 mm) underwent EUS-LA. Treatment outcomes were assessed and predictive factors were calculated via univariate and multivariate analyses. Results Twenty-five tumors achieved complete ablation after the first or second session of EUS-LA. The treatment effectiveness was 100%. During a median follow up of 27 months (3–60), four tumors (16%) developed local tumor progression and 15 patients (75%) experienced intrahepatic distant recurrence. According to univariate and multivariate analyses, the significant prognostic factor of local tumor progression was tumor size >2 cm (p = 0.047). Significant prognostic factors of intrahepatic distant recurrence were: tumor number, alpha-fetoprotein level, and total bilirubin level (p = 0.020, 0.019, 0.010, respectively). No adverse events related to EUS-LA were observed. Conclusion EUS-LA is a viable, safe, and effective treatment option for patients with liver tumor in the caudate lobe. Tumor size >2 cm increases the risk of post-procedural local tumor progression. Intrahepatic tumor number, and pretreatment alpha-fetoprotein level and total bilirubin level are associated with intrahepatic distant recurrence. Registration Clinicaltrials.gov, ID: NCT02816944(June 29, 2016)

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma.

Atezolizumab plus bevacizumab and lenvatinib are the key drugs in the current systemic chemotherapeutic regimen for hepatocellular carcinoma (HCC). Studies have reported the potential effectiveness of lenvatinib introduction after an atezolizumab plus bevacizumab treatment; however, the therapeutic effectiveness of a lenvatinib rechallenge after an atezolizumab plus bevacizumab treatment remains unclear. Thirteen consecutive patients who were rechallenged with lenvatinib after clinical failure following treatments with lenvatinib and atezolizumab plus bevacizumab were included. A comparative study was conducted on the duration and treatment efficacy of the first and second lenvatinib treatments and on the pre- and post-treatment liver function. The median ratios of the 1-month post-treatment alpha-fetoprotein (AFP) levels to the pretreatment AFP levels were 0.750 and 0.667 for the first and second lenvatinib treatments, respectively, without significant difference (p=0.9327). Meanwhile, the median ratios of the 1-month post-treatment albumin-bilirubin (ALBI) scores to the pretreatment ALBI scores were 1.063 and 0.827 for the first and second lenvatinib treatments, respectively, with significant difference (p=0.015). The median duration of the second lenvatinib treatment was significantly shorter than that of the first lenvatinib treatment [2.8 months (range=0.9-4.7 months) vs. 8.7 months (range=3.1-29.7 months)]. Lenvatinib re-administration after atezolizumab plus bevacizumab treatment can act as a double-edged sword, as it exerts an anti-tumor effect while being associated with potential liver function deterioration. However, this treatment sequence can be useful, and requires careful monitoring of the transitions in the liver function and the patient's performance status.

Prognostic Values of Alpha-Fetoprotein and Des-Gamma-Carboxyprothrombin in Hepatocellular Carcinoma in China: An Analysis of 4792 Patients.

BackgroundThe importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined.Patients and MethodsA total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately.ResultsA total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits.ConclusionThe present study comprehensively explored the clinical value of classical tumour markers for HCC using the “point-to-line” method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.

Feasibility of SBRT for hepatocellular carcinoma in Brazil - a prospective pilot study.

The aim of the study was to evaluate the feasibility and safety of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma in Brazil. SBRT is an evolving treatment in HCC patients not candidates to other local therapies. Its adoption in clinical practice has been heterogeneous, with lack of data on its generalizability in the Brazilian population. We conducted a prospective pilot study involving HCC patients after failure or ineligibility for transarterial chemoembolization. Patients received SBRT 30 to 50 Gy in 5 fractions using an isotoxic prescription approach. This study is registered at clinicaltrials.gov NCT02221778. From Nov 2014 through Aug 2019, 26 patients received SBRT with 40 Gy median dose. Underlying liver disease was hepatitis C, hepatitis B and alcohol-related in, respectively, 50%, 23% and 19% of patients. Median lesion size was 3.8 cm (range, 1.5-10 cm), and 46% had multiple lesions. Thirty-two percent had tumor vascular thrombosis; median pretreatment alpha-fetoprotein (AFP) was 171.7 ng/mL (range, 4.2-5,494 ng/mL). 1y-local progression-free survival (PFS) was 86% (95% CI: 61% to 95%), with higher local control in doses ≥ 45Gy (p = 0.037; HR = 0.12). 1y-liver PFS, distant PFS and OS were, respectively, 52%, 77% and 79%. Objective response was seen in 89% of patients, with 3 months post-SBRT median AFP of 12 ng/mL (2.4-637 ng/mL). There were no grade 3 or 4 clinical toxicities. Grade 3 or 4 laboratory toxicities occurred in 27% of patients. SBRT is feasible and safe in patients unresponsive or ineligible for TACE in Brazil. Our study suggests doses ≥ 45 Gy yields better local control.

Pretreatment serum alpha fetoprotein and its relation to sustained virologic response in patients with chronic HCV infection treated with direct-acting antiviral therapy

Background and study aim. The introductionof directacting antiviral agents (DAAs) hasincreased sustained virologic response (SVR) rates inpatients with chronic hepatitis C infection (CHC). Theaim of this study is to evaluate the efficacy of DAAsin treatment of Egyptian patients with CHC, and todetermine the parameters associated with non-responseto DAAs Patients and methods. This study included200 treatment-naive chronic hepatitis C patients whowere divided into two groups and treated accordingto the Egyptian National Treatment Program forHepatitis C Virus. Group 1 consisted of 100 easy-totreatpatients who were administered sofosbuvir 400mg daily/daclatasvir 60 mg daily for 3 months, whilegroup 2 included 100 difficult-to-treat patients treatedby Sofosbuvir 400 mg/ daclatasvir 60 mg /ribavirindaily for 3 months Results. The overall patient sustainedvirologic response (SVR) in the present studywas 93.5% (187/200). SVR in group 1 was 100%, whilegroup 2 showed SVR of 87% (87/100). Comparisonbetween patients with and without SVR revealed nostatistically significant differences regarding age andsex distribution, serum albumin, bilirubin, transaminaseslevel, INR and platelets count. However,patients who were non-responders had signi-ficantlyhigher pre-treatment alpha fetoprotein (AFP) levelsthan responders Conclusions. Treatment of CHCpati-ents with DAAs is associated with highersustained virologic response, particularly in easy-totreatpatients. AFP level may aid in prediction ofnon-responders to DAAs

Predictors of Failure and Survival in Patients with Hepatocellular Carcinoma Treated with Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) has been used as an effective treatment or as a bridge to liver transplant in patients with hepatocellular carcinoma (HCC). Despite high published rates of local control, failures can occur. In this study, we report our single institution experience and analyze treatment- and patient-related factors predicting for failure and overall survival. We performed a retrospective analysis of HCC patients treated with SBRT at our institution between 6/2007 and 1/2017. Biological effective dose (BED) was calculated using alpha/beta = 10. Failure was defined as in-field if happened within 80% isodose line, out-field if failure happened outside 80% isodose line but within the liver, and distant if failure occurred outside the liver. Absolute lymphocyte count (ALC) nadir was defined as the lowest ALC within 2 months after SBRT and the cut off used to define low ALC nadir was < 0.5 k cells/ul. Statistical analysis was done using chi-squared testing, logistic regression, and Kaplan -Meier methods. We identified 92 patients with a median age of 63 years (IQR 57-76 years); 71% were male; 72% had Child Pugh A and 64% had ECOG of 1. The most common cause of HCC was hepatitis C (56%) followed by non-alcoholic steatohepatitis(24%). The median tumor size was 26 mm (range 12-148 mm), with a median dose of 48 Gy (range 20-50 Gy) and median BED of 124.8 (range of 28-133). With median follow-up of 19.5 months, there were 21 (22.8%) patients with any failure: 5 (22%) were in-field, 13 (%64) were out-of-field, and 5 (%22) were distant metastases. Of note, 2 patients had concurrent in- and out-field failure. Progression free survival was 18 months (range 2-97 months). The mortality rate was 36% and 52% in patients who developed any type of failure. Univariate analysis revealed that pre-treatment alpha fetoprotein (AFP) is associated with risk of any failure (p=0.04). In addition, pre-treatment International Normalized Ratio (INR) is associated with risk of in-field failure (p=0.007). BED or dose were not associated with any failure (p=0.49, p=0.37). Patient with low ALC nadir had a lower overall survival (OS, 13 months versus 30 months, p-value=0.006) Baseline, 3-month and 1-year AFP were not associated with time to any failure (p=NS). In-field failure was associated with improved OS (p=0.03). Distant failure was associated with higher rate of mortality (p=0.004). We report our single institution experience of treating HCC patients with SBRT to define factors associated with failure and survival. The rate of any failure was 22.8% with low in-field failure (5.4%) after SBRT. The only factor associated with any failure was baseline AFP. Low ALC nadir was also associated with lower OS. These factors should be evaluated prospectively for validation.

Hepatocellular Carcinoma Occurrence/Recurrence after Direct-Acting Antivirals for Hepatitis C in Egyptian Cohort: Single-Center Experience

Background: Conflicting data have been published about the risk of hepatocellular carcinoma (HCC) following direct-acting antivirals (DAAs). We investigated the incidence of HCC occurrence/recurrence after DAAs therapy. Patients and Methods: Retrospectively, we analyzed data of 392 patients with F3–4 fibrosis and cirrhosis treated by DAAs during the period from August 2015 to May 2018. In HCC-experienced patients, HCC treatment modality, and the duration between HCC management and DAAs initiation were recorded. In all patients, pretreatment clinicolaboratory evaluation, and imaging before, during and after DAAs were done. Results: De novo HCC occurred in 7.6% of naïve patients, while recurrence appeared in 28% of patients with previous HCC. Pretreatment alpha-fetoprotein was an independent predictor of HCC occurrence, while the time between HCC ablation and the beginning of DAAs was the only predictor of HCC recurrence (p < 0.001). Half of the patients who started DAAs before 6 months had HCC recurrence, while patients who started DAAs at ≥6 months had no recurrence (p< 0.0001). Conclusions: Although HCC occurrence after DAAs was not high, recurrence was apparently high. Pretreatment alpha-fetoprotein is a predictor for de novo HCC. The time between HCC ablation and DAAs was the strongest predictor of recurrence.

Prognostic Role of Serum Alpha-Fetoprotein in Hepatocellular Carcinoma Patients with Radiofrequency Ablation

Background and study aim: Prognostic value of serum alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) is still debatable. We aimed to study this role in HCC patients who underwent radio-frequency ablation (RFA). Materials and Methods: Records from HCC patients were retrospectively analyzed between January 2012 and December 2016. A minimum data set for each patient record of a follow-up period of at least 1 year was pre-defined before enrollment. In all, 153 patients were enrolled. AFP levels were recorded for all patients at the time of diagnosis, 1 month after RFA and at 3-month intervals afterward. Patients were divided according to pretreatment AFP level into 3 groups: group 1: AFP 200 ng/mL. Results: Pretreatment AFP is not significantly correlated with age, baseline lesion number or size, baseline Child score or class, post RFA recurrence or death. The overall survival rates were 95%, 75.6%, 55.6%, 48.8%, and 48.8% at 1,2,3,4, and 5 years respectively. On comparing the 3 groups on disease-free survival, there was no statistically significant difference among the three classes. Child class A patients showed statistically significant better survival after RFA than those with Child class B. The ROC curve showed that AFP had inadequate accuracy to discriminate survivors and deceased patients and to discriminate patients with recurrence from those without recurrence. Conclusion: AFP level could not be used as a good predictor of either death or recurrence of HCC after RFA

Prognostic role of serum alpha-fetoprotein in hepatocellular carcinoma patients with radiofrequency ablation

Background/purpose: Prognostic value of serum alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) is still debatable. We aimed to study this role in HCC patients who underwent radiofrequency ablation (RFA). Methods: Records from HCC patients were retrospectively analyzed between January 2011 and December 2015. A minimum data set for each patient record of a follow-up period of at least 1 year was pre-defined before enrollment. In all, 153 patients were enrolled. AFP levels were recorded for all patients at the time of diagnosis, 1 month after RFA and at 3-month intervals afterward. Patients were divided according to pretreatment AFP level into 3 groups: group 1: AFP &lt;20ng/mL, group 2: AFP 20-200ng/mL and group 3: AFP &gt;200ng/mL. Results: Pretreatment AFP is not significantly correlated with age, baseline lesion number or size, baseline Child score or class, post RFA recurrence or death. The overall survival rates were 95%, 75.6%, 55.6%, 48.8%, and 48.8% at 1, 2, 3, 4, and 5years respectively. On comparing the 3 groups on disease-free survival, there was no statistically significant difference among the three classes. Child class A patients showed statistically significant better survival after RFA than those with Child class B. The ROC curve showed that AFP had inadequate accuracy to discriminate survivors and deceased patients and to discriminate patients with recurrence from those without recurrence.

Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral aetiology \u2013 a prospective study

BackgroundAlpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear.MethodsPatients with nvHCC, referred to a Hepatobiliary Clinic from September 2011–2015 were screened. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated against patient characteristics, tumour characteristics and survival.ResultsThree hundred eighty-nine patients with nvHCC [age 64(12–88) years; 344(88.4%) males] were screened. Median AFP was 25.46 ng/ml (1.16–100,000). 41.2% (n = 160) Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05), late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels. Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was associated with longer survival (16 vs. 7 months, P < 0.001).ConclusionPre treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over 400 ng/ml was associated with aggressive tumour behaviour and poor prognosis.

Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy

To correlate the imaging findings of treated hepatocellular carcinoma (HCC) after stereotactic body radiation therapy (SBRT) with explant pathology and alpha-fetoprotein (AFP) response. From 2007 to 2015, of 146 patients treated with liver SBRT for Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma, 10 were identified with inclusion criteria and had regular interval follow-up magnetic resonance imaging/triple phase computed tomography and explant pathology or declining AFP values for radiology-pathology response correlation. Reference standards for successful response were >90% necrosis on explant pathology or pretreatment AFP >75ng/mL normalizing to <10ng/mL within 1year after SBRT without other treatment. Subjects were treated with 24 to 50Gy in 3 to 5 fractions. Multiphasic magnetic resonance imaging or computed tomography performed at 3, 6, 9, and 12months after SBRT was compared with pretreatment imaging by 2 expert radiologists. Descriptive statistics were calculated. There were 10 subjects with 10 treated HCCs, classified as 3 Organ Procurement and Transplantation Network (OPTN) 5a, 4 OPTN 5b, and 3 OPTN 5x. All had successfully treated HCCs, according to explant pathology or declining AFP. Four of 10 HCCs had persistent central arterial hyperenhancement 3 to 12months after SBRT; persistent wash-out was common up to 12months (9 of 10). Of 10 treated HCCs, 9 exhibited decreased size at 12months. Liver parenchyma adjacent to the lesion showed early (3-6months) hyperemia followed by late (6-12months) capsular retraction and delayed enhancement. No patient had a significant decline in liver function. In the absence of increasing size, persistent central arterial hyperenhancement and wash-out can occur within the first 12months after SBRT in successfully treated HCCs and may not represent residual viable tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiologic signature of tumor control is determined, freedom from local progression seems to be the best measure of HCC control after SBRT.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients.

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101.

BackgroundThe systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101.MethodsThe data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs).ResultsThe estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or CLIP scores alone.ConclusionsThe NLR-PLR score is a more powerful predictive system than the other inflammation-based scores for patients with HCC who were treated with TACE and H101. The predictive ability may be improved by utilizing a combination of the NLR-PLR and CLIP scores.

Nine-year experience of doxorubicin-eluting beads chemoembolization for hepatocellular carcinoma

Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efficacy and survival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment. This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of computed tomography and serum alpha-fetoprotein (AFP). Multivariate analysis was used to determine the factors affecting tumor response. The median post-treatment to pre-treatment AFP level was 0.8 for a DEB session (n=258) and 1.0 for a cTACE session (n=452), showing a significantly greater decrease in AFP after DEB (P<0.05). More patients in the DEB group achieved objective response (complete and partial) compared with those in the cTACE group (P<0.05). Objective tumor response after DEB vs cTACE was 34.8% vs 15.4% in 0-3 months (P=0.001), 37.1% vs 20.0% in 3-6 months (P<0.05), and 50.0% vs 30.0% in 6-12 months (P=0.093). DEB predicted a 3.604 times odds of achieving at least one objective tumor response in a patient when compared to cTACE (P<0.0001). The median survival from first transcatheter therapy of patients having undergone at least once DEB was 12.53 months, while those having received cTACE only was 10.53 months (P=0.086). A tendency of improved survival appeared to maintain until >80 months after the first TACE session in the DEB group. DEB is a safe alternative to cTACE in HCC patients with better therapeutic efficacy.

Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

We report on the long-term intention-to-treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4-5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4-5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan-Meier's 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5-year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha-fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04). Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4-5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup.

Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development.

To investigate risk factors for development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-related liver cirrhosis (LC-C). To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon (IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging. HCC was diagnosis in 50 (21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older (P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein (AFP) (P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio (OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/mL (P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin (DCP) levels of ≥ 40 mAU/mL at 24 wk after the completion of IFN and ribavirin therapy (P < 0.001, OR = 24.43, 95%CI: 4.11-238.67). We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.

Improved Serum Alpha-Fetoprotein Levels after Iron Reduction Therapy in HCV Patients

Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients. Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies. Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7 ng/mL, ALT from 96 to 50 IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28 IU/L, and ferritin from 191 to 10 ng/mL (P < 0.001 for each). The rate of decline in the AFP level correlated positively only with that in GGT (r = 0.695, P = 0.001), although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10 ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30 IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5–293; P = 0.024). Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients.