ALBI Grade Research Articles

Prognostic value of inflammatory and nutritional markers for hepatocellular carcinoma.

Many clinical studies have demonstrated that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and Onodera's prognostic nutritional index (OPNI) are visibly involved in the prognosis of a variety of tumors. In our research, we aim to determin the prognostic impact of NLR, PLR, and OPNI for hepatocellular carcinoma (HCC).Data of hepatocellular carcinoma patients undergoing treatment in Changzhi People's Hospital between 2011 and 2017 were reviewed. 270 patients with HCC were under inclusion criteria. The optimal cut-off points of OPNI, NLR and PLR were determined by using the X-tile program. The overall survival (OS) was analyzed by Kaplan–Meier method. Multivariate analysis was performed using Cox Proportional Hazard Regression model to determine independent prognostic indicators for HCC.As revealed by Univariate and multivariate analysis, OPNI, Treatment, PLR, and BCLC Stage can be used as independent prognostic indicators for HCC. Comparing the P values and hazard ratios, we found out that the OPNI has greatest influence on prognosis in these indexes. The appropriate cut-off points of NLR, PLR, and OPNI were 2.5, 133.3, and 39.5, respectively. High score OPNI group had a better OS. In the analysis between OPNI and clinicopathological characteristics, there were differences in treatment, postoperative therapy, AST, ALBI grade, NLR and PLR between the high OPNI group and the low OPNI group, while others did not.OPNI is a straightforward and effective independent prognostic indicator for HCC.

The PATH score based on pathological grade predicts survival of patients with advanced hepatocellular carcinoma after hepatic arterial infusion chemotherapy.

e16134 Background: Hepatic arterial infusion chemotherapy (HAIC) is an emerging and effective therapeutic strategy for advanced hepatocellular carcinoma (HCC). We developed a practical prognostic score for patients undergoing HAIC to determine who can benefit from it. Methods: Between 2014 and 2019, 482 treatment-naïve patients with advanced HCC undergoing HAIC were included from two independent treatment departments. Patients were randomly divided into training (n = 337) and validation (n = 145) cohorts. Pathological grade, ALBI grade, and TNM stage were selected and developed a simple score to evaluate HAIC treatment (PATH) by Cox regression model, subsequently confirmed in the validation cohort and compared with other prognostic scores. Results: According to the PATH score, patients were divided into three groups; low-risk (0-1 point), moderate-risk (2-3 points), and high-risk (4-6 points). The median survival in the low-risk group was significantly longer than those in the other two groups (34.9 [95% CI: 25.8-44.0] vs. 13.6 [95% CI: 11.3-15.9] vs. 8.0 [95% CI: 6.8-9.2] months; p <0.001). The PATH score was fairly confirmed in the validation cohort and consistently performed better than other existing models in the training and validation cohorts. Conclusions: PATH score may be a simple and practical tool, which has good discrimination ability to screen HAIC sensitive populations and effectively predict individual survival outcomes. Calculation method of the PATH score.[Table: see text]

Efficacy and predictors of survival in patients with solitary hepatocellular carcinoma larger than 5 cm undergoing transarterial chemoembolization

AbstractFor patients with solitary hepatocellular carcinoma (HCC) larger than 5 cm not suitable for surgical resection, transarterial chemoembolization (TACE) is an alternative treatment. However, the response rate and survival predictors after TACE remain unclear. This study aimed to evaluate the treatment response and survival in this population. Consecutive 161 treatment‐naïve patients with solitary HCC larger than 5 cm undergoing TACE as the initial treatment were retrospective enrolled. Radiologic response after first TACE was evaluated by modified RECIST criteria. Factors associated with overall survival (OS) were analyzed. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were observed in 8.7%, 24.8%, 32.9%, and 36% of patients, respectively. The median OS in patients with CR, PR, SD, and PD were 71.4, 44.8, 17.7, and 14.3 months, respectively. By multivariate analysis, tumor size greater than 10 cm (odds ratio = 0.403, P = .023) was the only factor associated with radiologic response. By multivariate analysis, ALBI grade 2 or 3 (hazard ratio [HR] = 2.169, P = .001), tumor size greater than 7 cm (HR = 1.833, P = .010), and achieving complete or partial response (HR = 0.505, P = .003) were independent predictors of OS. An ALBI‐Response‐Size (ARS) score was developed to classify patients into low, intermediate and high risk of mortality (median OS of 68.6, 27.1, and 12.5 months, respectively, P < .001). In conclusion, ALBI grade, tumor size, and radiologic response are important predictors of survival in patients with solitary HCC larger than 5 cm undergoing TACE. A prognostic model can be applied to discriminate patient's survival after TACE.

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization.

Simple SummaryRadioembolization has failed to prove survival benefit in randomized trials, and, depending on various factors including tumor biology, response rates may vary considerably. Studies showed positive correlations between survival and absorbed tumor dose. Therefore, increasing currently prescribed tumor doses may be favorable for improving patient outcomes. The dominant limiting factor for increasing RE dose prescriptions is the relatively low tolerance of liver parenchyma to radiation with the possible consequence of a radiation-induced liver disease. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. Our study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients. The results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis to increase dose prescriptions in radioembolization.Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Modified albumin-bilirubin grade to predict eligibility for second-line therapies at progression on sorafenib therapy in hepatocellular carcinoma patients.

Our aim is to evaluate the utility of liver function measured by modified albumin-bilirubin (mALBI) grade to predict eligibility for second-line therapies, including regorafenib and ramucirumab therapy, at initiation of sorafenib therapy for patients with hepatocellular carcinoma (HCC). Participants in this retrospective, single-center study comprised 197 patients with sorafenib-treated HCC, Child-Pugh scores (CPs) 5-7 and performance status 0-1 treated between October 2009 and June 2019. The factors at initiation of sorafenib therapy, including mALBI grade and CPs, were analyzed with regard to second-line eligibility, regorafenib eligibility and ramucirumab eligibility, respectively. Proportions of eligibility for second-line therapies, regorafenib therapy and ramucirumab therapy were 48.7%, 35.5% and 18.3%. Modified ALBI grades 1 and 2a were contributing factors for second-line eligibility (odd ratios [OR] 16.7 and 5.6; 95% CI 6.5-43.3 and 2.6-12.2), regorafenib therapy (OR 13.9 and 6.9; 95% CI 5.6-34.4 and 2.9-16.2), and ramucirumab therapy (OR 9.5 and 4.8; 95% CI 2.9-30.8 and 1.6-14.4), with grade 2b defined as reference. Patients with mALBI grade 1 and CPs 5 exhibited especially high proportion of eligibility for regorafenib therapy (70.5%). In patients with mALBI grade 2b, those with CPs 5 displayed higher proportion of eligibility for second-line therapy and ramucirumab therapy (100% and 50%) than those with CPs 6 (31.8% and 11.4%). Modified ALBI grade in combination with CPs at the initiation of sorafenib therapy would be useful to predict eligibility for second-line therapies.

Patterns, timing, and predictors of recurrence after laparoscopic liver resection for hepatocellular carcinoma: results from a high-volume HPB center

BackgroundAlthough long-term outcomes may be comparable between laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC), there has been little discussion regarding the patterns of recurrence after LLR.MethodsPatients with HCC who underwent hepatectomy between April 2015 and November 2018 were included in this study. The recurrence patterns were analyzed in detail. The recurrence outcomes following laparoscopic versus OLR for HCC were compared after 1:2 propensity score matching. Potential risk factors for recurrence were also assessed with Cox proportional risk models.ResultsAmong 425 patients after LLR, 144 (33.8%) experienced recurrence at the last follow-up, with a median recurrence-free survival (RFS) of 10.0 months (range 1–58 months). The most frequent recurrence site was the liver (n = 99, 68.8%), followed by the surgical margin (n = 15, 10.4%) and distant metastases (n = 12, 8.3%). Liver recurrence with distant metastasis (n = 10, 6.9%) tended to occur early (median 8.0 months), while peritoneal recurrence (n = 8, 5.6%) occurred later (median 14.0 months). A total of 120 (83.3%) patients had recurrence within 2 years after LLR. No trocar site recurrence was observed in this study. The recurrence patterns, timing, and treatment did not show significant differences between the LLR and OLR. The independent risk factors for recurrence included ALBI grade, postoperative α-fetoprotein > 8 ng/ml, tumor size > 5 cm, surgical margin ≤ 1 cm, and multiple tumors. Patients with recurrence had 1- and 5-year overall survival rates of 81.1% and 60.7%, respectively, compared with rates of 95.8% and 92.9% for patients without recurrence (P < 0.000).ConclusionThis study suggested that intrahepatic recurrence was still the most common recurrence pattern for HCC after LLR and that LLR did not increase the risk of trocar hole recurrence or implantation. Most cases of recurrence occurred within 2 years after LLR, suggesting that surveillance should be targeted to early recurrence.

A change in the timing for starting systemic therapies for hepatocellular carcinoma: the comparison of sorafenib and lenvatinib as the first-line treatment.

The aim of this retrospective multicenter study was to evaluate the differences in the timing for starting systemic therapies as the first-line treatment for hepatocellular carcinoma (HCC). A total of 375 patients with HCC treated with sorafenib from May 2009 to March 2018 and 56 patients treated with lenvatinib from March 2018 to November 2018 at our affiliated hospitals were included in this study. The median ages of the sorafenib and lenvatinib groups were 71.0 (interquartile range [IQR]: 64.0-77.0) and 73.5 (IQR: 68.0 -80.0) years old, and 300 (80.0%) and 42 (75.0%) patients were men, respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate and advanced in 39 patients (10.4%), 133 patients (35.5%) and 203 patients (54.1%) in the sorafenib group and 1 patient (1.8%), 17 patients (30.4%) and 38 patients (67.9%) in the lenvatinib group, respectively. In the analysis of intermediate HCC, patients who satisfied the criteria of TACE failure/refractoriness (P=0.017), those with ALBI grade 1 (P=0.040), and those with a serum AFP level < 200 ng/ml (P=0.027) were found more frequently in the lenvatinib group than in the sorafenib group, with statistical significance. The objective response rate (ORR) of lenvatinib was 34.8% in the overall patients and 46.7% in the intermediate-stage HCC patients, which was significantly higher than sorafenib (P=0.001, P=0.017). The emergence of lenvatinib has encouraged physicians to start systemic chemotherapy earlier in intermediatestage HCC patients.

Post hoc analysis in patients (pts) with unresectable hepatocellular carcinoma (uHCC) who progressed to Child-Pugh B (CPB) liver function in the phase III REFLECT study of lenvatinib (LEN).

298 Background: The treatment landscape for pts with uHCC has recently expanded. However, there is an unmet need for effective treatment options in CPB pts. LEN is approved first-line in uHCC based on the REFLECT study (Child-Pugh A [CPA] pts were allowed, per inclusion criteria). In a prior analysis of REFLECT, pts treated with LEN benefited irrespective of baseline liver function (ALBI grade 1 or 2; Child-Pugh score 5 or 6). To determine outcomes in pts with reduced liver function, we report a post hoc analysis of key efficacy and safety results in LEN-treated pts from REFLECT who progressed to CPB and those who did not within the first 8 weeks of treatment. Methods: In REFLECT, pts with uHCC were randomized 1:1 to LEN (per bodyweight: 12 mg/day for ≥60 kg; 8 mg/day for &lt; 60 kg) or sorafenib (400 mg twice daily) in 28-day cycles. This analysis assessed ORR. Landmark analyses (starting at week 8) of PFS, time-to-progression (TTP), and OS in CPB pts and in pts who remained CPA at 8 weeks post-randomization were also conducted. Tumors were assessed by mRECIST by independent imaging review. Safety was also assessed from baseline. Results: This subgroup analysis included LEN-treated pts (n = 60) who progressed to CPB within the first 8 weeks of treatment (CPB pts) and 413 pts who did not (CPA pts). At baseline, 26.7% and 73.1% of pts had an ALBI grade of 1 and 73.3% and 26.9% of pts had an ALBI grade of 2 in CPB and CPA pts, respectively. ORR was 28.3% (95% CI 16.9–39.7) for CPB pts and 42.9% (95% CI 38.1–47.6) for CPA pts. A landmark analysis showed a median PFS of 3.7 mos (95% CI 1.8–7.4) for CPB pts and 6.5 mos (95% CI 5.6–7.4) for CPA pts from the week 8 timepoint. Landmark analyses at week 8 also showed that the median TTP was 5.6 mos (95% CI 3.5–9.3) for CPB pts and 7.3 mos (95% CI 5.6–7.4) for CPA pts; the median OS was 6.8 mos (95% CI 2.6–10.3) for CPB pts and 13.3 mos (95% CI 11.6–16.1) for CPA pts per week 8 landmark analyses. As expected, efficacy appeared to be greater in CPA pts versus CPB pts; however, OS of 6.8 months in CPB pts after the week 8 landmark is notable. Moreover, median duration of treatment was 3.2 mos for CPB pts and 6.9 mos for CPA pts, thereby suggesting CPB pts can remain on LEN. The incidence of grade ≥3 treatment-related AEs (TRAEs) was 71.7% in CPB pts and 54.7% in CPA pts. TRAEs leading to discontinuation occurred in 18.3% of CPB pts and 7.5% of CPA pts. Conclusions: In this post hoc analysis of pts in REFLECT, we examine the key efficacy and safety results for LEN-treated pts who progressed to CPB by week 8. This post hoc analysis is limited by its descriptive nature; however, the results indicate that further study of LEN in CPB pts with uHCC is warranted. Clinical trial information: NCT01761266.

Development and Validation of a Contrast-Enhanced CT-Based Radiomics Nomogram for Prediction of Therapeutic Efficacy of Anti-PD-1 Antibodies in Advanced HCC Patients.

BackgroundThere is no study accessible now assessing the prognostic aspect of radiomics for anti-PD-1 therapy for patients with HCC.AimThe aim of this study was to develop and validate a radiomics nomogram by incorporating the pretreatment contrast-enhanced Computed tomography (CT) images and clinical risk factors to estimate the anti-PD-1 treatment efficacy in Hepatocellular Carcinoma (HCC) patients.MethodsA total of 58 patients with advanced HCC who were refractory to the standard first-line of therapy, and received PD-1 inhibitor treatment with Toripalimab, Camrelizumab, or Sintilimab from 1st January 2019 to 31 July 2020 were enrolled and divided into two sets randomly: training set (n = 40) and validation set (n = 18). Radiomics features were extracted from non-enhanced and contrast-enhanced CT scans and selected by using the least absolute shrinkage and selection operator (LASSO) method. Finally, a radiomics nomogram was developed based on by univariate and multivariate logistic regression analysis. The performance of the nomogram was evaluated by discrimination, calibration, and clinical utility.ResultsEight radiomics features from the whole tumor and peritumoral regions were selected and comprised of the Fusion Radiomics score. Together with two clinical factors (tumor embolus and ALBI grade), a radiomics nomogram was developed with an area under the curve (AUC) of 0.894 (95% CI, 0.797–0.991) and 0.883 (95% CI, 0.716–0.998) in the training and validation cohort, respectively. The calibration curve and decision curve analysis (DCA) confirmed that nomogram had good consistency and clinical usefulness.ConclusionsThis study has developed and validated a radiomics nomogram by incorporating the pretreatment CECT images and clinical factors to predict the anti-PD-1 treatment efficacy in patients with advanced HCC.

Liver scoring system and hepatectomy outcomes: a veterans affairs corporate data warehouse analysis

Presenter: Yazan Ashouri MD | University of Arizona Background: Several liver scoring systems have been introduced. The optimal predictive liver scoring system for hepatectomy outcomes is yet to be defined. Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) and VA Informatics and Computing Infrastructure (VINCI) were utilized to identify veterans who underwent hepatectomy between 2008-2018. Logistic regression was performed to evaluate the association between ALBI grade, FIB4 and APRI with 90-day mortality and cirrhosis decompensation after surgery. Receiver operating characteristic (ROC) curves and Youden index were performed to determine optimal cutoff values. Kaplan-Meier method and log-rank test were used for survival analysis. Results: A total of 1477 veterans underwent hepatectomy in VA hospitals during the study period. Most of the patients were white (60.2%), males (97%) and underwent surgery for hepatocellular carcinoma (62.8%), followed by colorectal liver metastases (20.3%) and biliary cancers (11.2%). Partial hepatectomy was the most common operation (73.5%) followed by right hepatectomy (12.3%). The 90-day mortality was 5.1% and the rate of cirrhosis decompensation, with development of ascites or encephalopathy within 90 days from surgery, was 9.8%. Multivariable logistic regression showed that FIB4 and APRI were associated with 90-day mortality: Odds Ratio (OR): 1.17, Confidence interval (CI) 1.07-1.28 (p 2 was not associated with 90-day mortality (OR: 1.60, CI: 0.86-2.97). FIB4 and APRI were also independently associated with cirrhosis decompensation within 90 days: OR: 1.18, CI: 1.09-1.28 (P < .0001) and OR: 1.29, CI: 1.11-1.51 (P < .001), respectively. ALBI grade was not associated with cirrhosis decompensation (OR:1.18, CI: 0.75-1.84). ROC curves evaluating the ability to predict cirrhosis decompensation showed areas under the curve (AUC) of 0.66 for FIB4 and 0.65 for APRI. Youden index analysis showed that the best cutoff values for FIB4 and APRI to be 2.56 and 0.70, respectively. Survival analysis revealed that patients with FIB4 ≥ 2.56 had worse overall survival (OS) than patients with FIB4 < 2.56, OS: 46.8 versus 62.4 months (Log-rank: P < .0001). Likewise, veterans with APRI ≥ 0.70 had worse survival when compared to veterans with APRI < 0.70, OS: 51.6 versus 60.8 months (Log-rank: P < .01). Conclusion: In this large cohort study, FIB4 and APRI were independently associated with 90-day mortality and post-hepatectomy cirrhosis decompensation. They were also shown to be associated with overall survival. These findings suggest that these non-invasive fibrosis markers could be useful in the preoperative selection criteria for hepatectomy.

Association of the Modified ALBI Grade With Endoscopic Findings of Gastroesophageal Varices.

This study aimed to assess the association of the modified albumin-bilirubin (mALBI) grade with the endoscopic findings of gastroesophageal varices (GEVs). A total of 141 patients with histologically proven cirrhosis who underwent a liver biopsy and esophagogastroduodenoscopy were enrolled. The relationships between the mALBI grade and endoscopic findings were evaluated. The incidence of GEVs and high-risk GEVs differed among mALBI grades. Patients with mALBI grades of 2b-3 had higher rates of GEVs and high-risk GEVs in comparison to those with mALBI grades of 1-2a (p<0.0001). In addition, patients with mALBI grade 2b or grade 3, but not those with mALBI grade 2a, had significantly higher rates of complicated GEVs and high-risk GEVs in comparison to those with mALBI grade 1. The mALBI grade may be useful in predicting the presence of GEVs and for stratifying their bleeding risk.

Predicting Operative Outcomes in Patients with Liver Disease: Albumin-Bilirubin Score vs Model for End-Stage Liver Disease-Sodium Score

The albumin-bilirubin score (ALBI) has recently been shown to have increased accuracy in predicting post-hepatectomy liver failure and mortality compared with the Model for End-Stage Liver Disease (MELD). However, the use of ALBI as a predictor of postoperative mortality for other surgical procedures has not been analyzed. The aim of this study was to measure the predictive power of ALBI compared with MELD-sodium (MELD-Na) across a wide range of surgical procedures. Patients undergoing cardiac, pulmonary, esophageal, gastric, gallbladder, pancreatic, splenic, appendix, colorectal, adrenal, renal, hernia, and aortic operations were identified in the 2015-2018 American College of Surgeons NSQIP database. Patients with missing laboratory data were excluded. Univariable analysis and receiver operator characteristic curves were performed for 30-day mortality and morbidity. Areas under the curves were calculated to validate and compare the predictive abilities of ALBI and MELD-Na. Of 258,658 patients, the distribution of ALBI grades 1, 2, 3 were 51%, 42%, and 7%, respectively. Median MELD-Na was 7.50 (interquartile range 6.43 to 9.43). Overall 30-day mortality rate was 2.7% and overall morbidity was 28.6%. Increasing ALBI grade was significantly associated with mortality (ALBI grade 2: odds ratio [OR] 5.24; p < 0.001; ALBI grade 3: OR 25.6; p < 0.001) and morbidity (ALBI grade 2: OR 2.15; p < 0.001; ALBI grade 3: OR 6.12; p < 0.001). On receiver operator characteristic analysis, ALBI outperformed MELD-Na with increased accuracy in several operations. ALBI score predicts mortality and morbidity across a wide spectrum of surgical procedures. When compared with MELD-Na, ALBI more accurately predicts outcomes in patients undergoing pulmonary, elective colorectal, and adrenal operations.

Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment.

Simple SummaryMany drugs has become available for the advanced hepatocellular carcinoma and sequential systemic therapies play an important role in the clinical settings. Because the key eligibility criteria for post-progression treatment included the performance status of ≦1 and Child-Pugh score of ≦6, to clarify the eligibility for post-progression treatment will provide meaningful information. The aim of this multicenter retrospective study was to investigate the predictive factors of progression to Child-Pugh class B, the formation of ascites and the candidates for post-progression treatment. Authors confirmed that male, ALBI grade 1, Child-Pugh score 5 (CP5A) and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and Child-Pugh score 6.The aim of this multicenter retrospective study was to assess the change in liver function in patients with hepatocellular carcinoma treated with lenvatinib. Among 139 consecutive patients receiving lenvatinib treatment between March 2018 and July 2019, 28 patients with Child-Pugh class B and one patient with inadequate patient information were excluded. Remaining 110 patients with Child-Pugh class A were analyzed. The median age of 110 patients was 73 years (IQR 66.7–80) and 88 patients (80.0%) were men. Child-Pugh score was 5 (CP5A) and 6 (CP6A) in 58 (52.7%) and 52 patients (47.3%), and ALBI grade was 1 and 2 in 38 (34.5%) and 72 patients (65.5%), respectively. The deterioration to Child-Pugh class B was found in 43 patients (39.1%) during the lenvatinib treatment. The favorable factors related to preserving liver function were significantly shown to be male, ALBI grade 1, CP5A and BCLC early or intermediate stage in the multivariate analysis. The formation of ascites was found in 32 patients (28.6%). The significant unfavorable factors associated with the formation of ascites were found to be low platelet count and CP6A. Among the 79 patients, there were 36 (45.6%) and 11 patients (13.9%) who fulfilled the criteria for candidate for the post-progression treatment and ramucirumab treatment, respectively. The predictive factors of the post-progression treatment were shown to be ALBI grade 1 and CP5A in multivariate analysis. In conclusion, male, ALBI grade 1, CP5A and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and CP6A.

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian Center.

Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety, however, are lacking. We conducted a retrospective review of all patients with advanced HCC seen at our center who received at least one dose of an ICI between May 2015 and June 2018. Data cutoff was December 31, 2018. Responses were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Of 114 patients, 88.6% were male. Median age was 66 years, 96.5% had an Eastern Cooperative Oncology Group of 0-1. 62.3% received monotherapy ICI. 18.4% of patients had Child-Pugh (CP) B disease on initiation of ICI, and 69.3% had an ALBI grade of 2. 54.4% were known to have chronic hepatitis B (HBV) or were previously infected, and 11.4% had hepatitis C. Baseline HBV viral load (VL) ranged from undetectable to 8210000 IU/mL. 35.1% received prior systemic treatment. 28.9% received prior sorafenib. Over a median follow-up duration of 13.8 months (10.4-15.8), ORR was 18.4%, and DCR was 50.9%. Median progression-free survival was 2.7 months (1.3-4.0), and median overall survival (OS) was 13.9 months (6.9-16.2). Thirty-one patients (27.2%) received further systemic therapy after ICI discontinuation. On multivariable analyses, lower albumin level, higher bilirubin level, diuretic-refractory ascites, and HBV-associated HCC were associated with poorer OS. 69.3% of patients experienced adverse events (AE) of any grade, 14.9% of these being grade 3-4. No grade 5 AE were observed. Use of antiviral therapy was associated with a lower risk of grade 3 or above hepatic AEs (P=0.048), whereas high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AE. We have demonstrated that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with CP A cirrhosis. While prognosis of patients with advanced HCC and CP B cirrhosis remains poor even with ICI, usage of ICI is likely to be safe. Patients with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.

The scoring systems in predicting short-term outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome characterized by acute and severe hepatic insults with high short-term mortality. This study aimed to compare the scoring systems which were used to predict short-term outcomes for HBV-ACLF patients. A total of 529 patients diagnosed as HBV-ACLF were retrospectively analyzed and randomly divided, at a ratio of 3:1, into derivation cohort (n=397) and validation cohort (n=132). Univariate and multivariate analyses were performed to determine the discriminative abilities of the ALBI grade in predicting 30-day and 90-day mortality. The area under the receiver operating characteristic (AUC) curves was used to evaluate the accuracy of models. The survival was associated with lower ALBI score, MELD score and CLIF-C ACLF score than death. In the derivation cohort, elevated ALBI score was related to worse prognosis (30-day mortality: HR =3.452; 90-day mortality: HR =3.822), increased MELD score was associated with worse overall survival (30- day mortality: HR =1.073; 90-day mortality: HR =1.082), and increased CLIF-C ACLF score was associated with worse overall survival (30-day mortality: HR =1.061; 90-day mortality: HR =1.065). The multivariate analyses identified the ALBI score, MELD score and CLIF-C ACLF score as independent prognostic predictors. The results of validation cohort validated these findings. Our study revealed that both the ALBI score, MELD score and CLIF-C ACLF score could predict 30- and 90-day mortality of HBV-ACLF accurately. Elevated ALBI score, MELD score and CLIF-C ACLF score were associated with worse prognosis.

Prognostic Nomogram for Patients with Hepatocellular Carcinoma After Thermal Ablation.

To develop an effective prognostic nomogram for patients with hepatocellular carcinoma (HCC) after thermal ablation. A total of 772 patients with intrahepatic primary or recurrent HCC who underwent radiofrequency ablation or microwave ablation between March 2011 and October 2016 were included. 602 patients (mean age, 56.0 ± 11.9years; 495 male/107 female) were included in the primary cohort to establish a prognostic nomogram. Significant prognostic factors for overall survival (OS) identified by Cox univariate and multivariate regression analyses were used to construct the nomogram. The remaining 170 patients (mean age, 55.9 ± 11.9years; 145 male/25 female) were used to validate the predictive accuracy of the nomogram. During a mean follow-up period of 26months (range 1-85months), the median OS periods were 48.6months and 44.0months for the primary and validation cohorts. The 1-, 3-, and 5-year OS rates were 85.5%, 61.4%, and 43.3% in the primary cohort and 84.7%, 59.6%, and 43.3% in the prospective validation cohort, respectively. Multivariate analysis found that pre-ablation treatment, AFP, CEA, CA19-9, ALBI grade, tumor number, and tumor size (hazard ratio > 1, P < 0.05) were independent risk factors for OS. A nomogram was developed based on these seven variables. The calibration curve for predicting the probability of survival showed a good agreement between the nomogram and actual observation both in the primary (concrete index: 0.699) and validation cohorts (concrete index: 0.734). This simple nomogram based on seven variables including ALBI grade offers personalized prognostic data for HCC patients after ablation. Level 4, case series.

SAT480 - ALBI grade is a good predictive parameter for prognosis in advanced HCC patients with nivolumab therapy

SAT480 - ALBI grade is a good predictive parameter for prognosis in advanced HCC patients with nivolumab therapy

Prognosis Factors of Young Patients Undergoing Curative Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma: A Multicenter Study.

BackgroundThe prognosis of young and older patients with hepatocellular carcinoma (HCC) is controversial. We aim to compare the clinicopathological features and prognosis of young (age ≤40 years) versus older patients (aged >40 years) with hepatitis B virus (HBV)-related HCC after curative resection.MethodsA total of 4504 patients with HBV-related HCC who underwent curative resection were included in this study and divided into young group (n=699) and older group (n=3805). Subgroup analyses were conducted to compare. Independent risk factors were identified by Cox regression analysis.ResultsYoung patients had better ALBI grade, lower rates of liver cirrhosis, higher rates of elevated serum AFP levels, larger tumor size, higher rates of microvascular invasion and macrovascular invasion, higher rates of Edmondson grade III–IV, lower rates of tumor capsular, more advanced AJCC TNM stages and more advanced BCLC stages than older patients (All p<0.05). Meanwhile, young patients had a worse overall survival (OS) rate (p=0.0091) and a worse recurrence-free survival (RFS) rate (p=0.045) than older patients. Multivariate analysis revealed that AFP, resection margin, tumor size, tumor capsular, and macrovascular invasion were associated with OS. The independent risk factors associated with RFS were ALB, tumor size, microvascular invasion, and macrovascular invasion.ConclusionYoung patients had better liver function, more aggressive tumor characteristics, and worse prognosis than older patients. A tumor size of ≥5 cm and macrovascular invasion were associated with poor OS and RFS in young patients. If tumors could be detected at the early stage by more frequent surveillance, long-term survival can be expected in the young patients.

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence and in vitro assessment via protein phosphorylation array.

The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group (p < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC50 of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR.

Comparison between Different Risk Scores in Predicting Hospital Mortality for Patients with Decompensated Liver Cirrhosis: A Single Center Study

Abstract Background: Predicting prognosis of patients with decom-pensated liver cirrhosis remains an important issue. Aim of Study: This study aimed to evaluate the predictive value of different patients' characteristics and risk scores as regard patients' outcome (death or survival). Patients and Methods: 672 patients with different com-plications of cirrhosis (gastrointestinal bleeding, hepatic encephalopathy, SBP, HRS and ascites) who were admitted to the National Liver Institute Hospital between 2015 and 2018 were included in this study. On admission to the hospital, assessment of patients by routine laboratory work-up (liver and kidney function tests and complete blood count), ultrasound of the abdomen, upper endoscopy for those with bleeding and ascitic fluid sampling for those with ascites. MELD, MELD-Na, CTP, ALBI and PALBI grades were calculated for all patients. At the end of hospitalization, patients outcomes were stratified as survived or died. Patients clinical and laboratory parameters were correlated with hospital mortality. Receiver Operating Curves (ROC) for risk scores were plotted to discriminate the predictive power of risk scores versus mor-tality. Results: The overall hospital mortality was 27.1%. Uni-variate analysis revealed age, total and direct bilirubin, albumin, transaminases, alkaline phosphatase, INR, serum creatinine, BUN, serum sodium and white cells count as significant, while multivariate analysis concluded age, total bilirubin, serum creatinine, Blood Urea Nitrogen (BUN), serum sodium (Na), INR and white blood cells count significance with hospital mortality, (p < 0.05). The area under receiver operating curve for MELD-Na was (0.85), MELD score (0.84), CTP score (0.82), AlBI grade (0.75) and PALBI grade (0.75), p < 0.001. Conclusion: MELD-Na and MELD scores are good pre-dictors for prognosis of patients with decompensated liver cirrhosis. But, ALBI and PALBI grade are promising scores which needs more validation.