Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.

AIMS: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. METHODS: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results. RESULTS: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS. CONCLUSION: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy.

Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.

AIM: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. METHODS: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed. RESULTS: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. CONCLUSIONS: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients.

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.

AIM: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. METHODS: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. RESULTS: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev. CONCLUSIONS: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

AIM: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. MATERIALS/METHODS: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. RESULTS: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. CONCLUSIONS: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal-gastric varices.

BACKGROUND: Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal-gastric varices (EGV). METHODS: From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively. RESULTS: The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3-14.0) vs. 10.5 months (95% CI 7.8-13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage. CONCLUSIONS: Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed.

Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study.

INTRODUCTION: Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population. METHODS: We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment. RESULTS: From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77). CONCLUSION: Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.

Lenvatinib as Second-Line Treatment after Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma: Clinical Results Show Importance of Hepatic Reserve Function.

INTRODUCTION: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure. METHODS: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D = 1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated. RESULTS: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, p = 0.557) or OS (13.6 months, p = 0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD = 3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD = 1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3 = 2:15:10), general fatigue (21.8%) (grade 1:2:3 = 3:13:6), protein in urine (16.8%) (grade 1:2:3 = 0:4:13), and hypertension (13.9%) (grade 1:2:3 = 1:8:5). CONCLUSION: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment.

Accurate SARC-F Score in Patients with Liver Disease.

SARC-F is a well-accepted screening tool for sarcopenia. A SARC-F value of 1 point is reported to be more discriminating in identifying sarcopenia than 4 points (recommended cutoff point). The prognostic impact of the SARC-F score was investigated in patients with liver disease (LD, n = 269, median age = 71 years, 96 hepatocellular carcinoma (HCC) cases). Factors associated with SARC-F ≥ 4 points and SARC-F ≥ 1 point were also examined. In the multivariate analysis, age (p = 0.048), and Geriatric Nutritional Risk Index (GNRI) score (p = 0.0365) were significant factors linked to SARC-F ≥ 1 point. In our patients with LD, the SARC-F score is well correlated with the GNRI score. The 1-year cumulative overall survival ratio in patients with SARC-F ≥ 1 (n = 159) and SARC-F 0 (n = 110) was 78.3% and 90.1% (p = 0.0181). After excluding 96 HCC cases, similar tendencies were found (p = 0.0289). In the receiver operating curve (ROC) analysis based on the prognosis for the SARC-F score, the area under the ROC was 0.60. The sensitivity was 0.57, the specificity was 0.62, and the optimal cutoff point of the SARC-F score was 1. In conclusion, sarcopenia in LDs can be affected by nutritional conditions. A SARC-F score of ≥1 is more useful than a score of 4 in predicting the prognosis of patients with LD.

Grip Strength in Patients with Gastrointestinal Diseases.

We sought to elucidate factors contributing to the grip strength (GS) decline in patients with gastrointestinal diseases (Ga-Ds, n = 602, 379 males, median age = 72 years). The GS decline in males and females was defined as <28 kg and <18 kg, respectively, following the current Asian guidelines. The median GS (male) was 28.8 kg, and GS decline (male) was found in 169 patients (44.6%). The median GS (female) was 17.5 kg, and GS decline (female) was found in 122 patients (54.7%). Advanced cancer was identified in 145 patients (24.1%). In terms of the univariate analysis of parameters of the GS decline, age (p < 0.0001), gender (p = 0.0181), body mass index (BMI, p = 0.0002), ECOG-PS (p < 0.0001), SARC-F score (p < 0.0001), hemoglobin value (p < 0.0001), total lymphocyte count (p < 0.0001), serum albumin value (p < 0.0001), C reactive protein (CRP) value (p < 0.0001), and estimated glomerular filtration rate were statistically significant. In terms of the multivariate analysis, age (p < 0.0001), BMI (p = 0.0223), hemoglobin value (p = 0.0186), serum albumin value (p = 0.0284), the SARC-F score (p = 0.0003), and CRP value (p < 0.0001) were independent parameters. In conclusion, the GS decline in patients with Ga-Ds is closely associated with not only the primary factor (i.e., aging) but also secondary factors such as inflammatory factors and nutritional factors.

The Relevance in the Neutrophil to Lymphocyte Ratio and the SARC-F Score in Gastrointestinal Diseases.

We sought to clarify the relevance in the neutrophil to lymphocyte ratio (NLR) and the SARC-F score in patients with gastrointestinal diseases (G-Ds, n = 672, median age = 73 years). Univariate and multivariate analysis for the SARC-F score were performed. Advanced malignancy was identified in 162 patients (24.1%). The median of NLR for all cases was 2.65. The median of NLR in ECOG-PS 0 (n = 436), 1 (n = 128), 2 (n = 49) and 3 or 4 (n = 59) was 2.26, 2.97, 4.41 and 5.99 (overall p < 0.0001). NLR had a significant correlation with the SARC-F score (r = 0.54, p < 0.0001). The median of NLR in the SARC-F score ≥4 (recommended value for sarcopenia, n = 84) and <4 (n = 588) was 5.87 and 2.48 (p < 0.0001). In all subgroup analyses, similar trends were seen. In the multivariate analysis, ECOG-PS (p < 0.0001) and NLR (p < 0.0001) were independent factors, while age had a trend for significance (p = 0.0686). In conclusion, we would like to emphasize the usefulness of NLR, a simple marker assessed only by blood tests, in predicting the possibility for sarcopenia by the SARC-F in G-Ds.

The Relationship between the SARC-F Score and the Controlling Nutritional Status Score in Gastrointestinal Diseases.

We sought to examine the relationship between the SARC-F score and the Controlling Nutritional Status (CONUT) score in patients with gastrointestinal diseases (GDs, n = 735, median age = 71 years, and 188 advanced cancer cases). The SARC-F score ≥ 4 (highly suspicious of sarcopenia) was found in 93 cases (12.7%). Mild malnutritional condition was seen in 310 cases (42.2%), moderate in 127 (17.3%) and severe in 27 (3.7%). The median SARC-F scores in categories of normal, mild, moderate and severe malnutritional condition were 0, 0, 1 and 1 (overall p < 0.0001). The percentage of SARC-F score ≥ 4 in categories of normal, mild, moderate and severe malnutritional condition were 4.4%, 12.9%, 26.8% and 25.9% (overall p < 0.0001). The SARC-F score was an independent factor for both the CONUT score ≥ 2 (mild, moderate or severe malnutrition) and ≥5 (moderate or severe malnutrition). In the receiver operating characteristic (ROC) curve analysis for the CONUT score ≥ 2, C reactive protein (CRP) had the highest area under the ROC (AUC = 0.70), followed by the SARC-F score (AUC = 0.60). In the ROC analysis for the CONUT score ≥ 5, CRP had the highest AUC (AUC = 0.79), followed by the SARC-F score (AUC = 0.63). In conclusion, the SARC-F score in patients with GDs can reflect malnutritional status.

The Management of Recurrence of Hepatocellular Carcinoma Occurring Within 6 Months After Hepatic Resection: A Comparative Study Using a Propensity Score Matching Analysis.

BACKGROUND: Hepatectomy is currently recommended as the most reliable treatment for hepatocellular carcinoma. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial. METHODS: Three-hundred thirty-nine patients who underwent hepatectomy were retrospectively analyzed using a propensity score matching analysis for the risk factors and outcomes for early recurrences within 6 months. The remnant liver volumes and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after surgery. The Student's t test and chi-square test, the likelihood-ratio test, Fisher's exact test, Mann-Whitney U test, or Wilcoxon signed-rank test were used in the statistical analyses. RESULTS: Early recurrence developed in 41/312 patients (13.1%). Vascular invasion and non-curative resection were independent risk factors for the occurrence of early recurrence (P < 0.001 and < 0.001, respectively). Patients with early recurrence had a poorer prognosis than patients who developed later recurrences (P < 0.001). Patients who underwent surgery or other local treatments had better outcomes (P < 0.001). The changes in remnant liver volumes and laboratory data after postoperative month 2 were not significantly different between the two groups. CONCLUSION: Patients with early recurrence within 6 months had a poorer prognosis than patients who developed a later recurrence. However, patients who underwent repeat hepatectomy for recurrences had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.

Comparison of SARC-F Score among Gastrointestinal Diseases.

SARC-F is a screening tool for sarcopenia. We sought to compare the SARC-F scores of patients with different gastrointestinal diseases (n = 1282 (762 males): upper gastrointestinal disease (UGD, n = 326), lower gastrointestinal disease (LGD, n = 357), biliary and pancreatic disease (BPD, n = 416), and liver disease (LD, n = 183)). Factors associated with SARC-F ≥4 points (highly suspicious of sarcopenia) were also examined. The median age was 71 years. Patients with SARC-F ≥4 points were found in 197 (15.4%). Advanced cancer was found in 339 patients (26.4%). The proportion of SARC-F ≥4 points in groups of UGD, LGD, BPD, and LD were 17.5% (57/326) in UGD, 12.0% (43/357) in LGD, 17.3% (72/416) in BPD, and 13.7% (25/183) in LD, respectively (overall p = 0.1235). In patients with and without advanced cancer, similar tendencies were observed. In the multivariate analysis, age (p < 0.0001), gender (p = 0.0011), serum albumin (p < 0.0001), lymphocyte count (p = 0.0019), C reactive protein (p = 0.0197), and the presence of advanced cancer (p = 0.0424) were significant factors linked to SARC-F ≥4 points. In patients with advanced cancer, SARC-F scores correlated well with their Glasgow prognostic scores. In conclusion, sarcopenia in gastrointestinal diseases may be affected not by disease type (i.e., the primary origin of the disease) but by aging, nutritional condition, inflammatory condition, and cancer burden.

Dysbiosis and liver diseases (Review).

Dysbiosis, a qualitative and quantitative aberrancy of gut microbiota, has attracted marked attention. At present, advances in molecular biological techniques have made it possible to analyze gut microbiota at the DNA and RNA levels without culturing, and methods such as 16S ribosomal RNA targeting analysis and metagenomic analysis using next­generation sequencers have been developed. The relationship between gut microbiota and various diseases has been extensively examined. Gut microbiota are essential for the immune system, energy intake and fat storage, and humans use them to build complex immune regulatory mechanisms and to obtain energy from food. The liver is the first organ to be nourished by the portal blood flow of intestinal origin, and liver diseases can be strongly influenced by various factors of intestinal origin, such as intestinal bacteria, bacterial components, and intestinal bacterial metabolites. Rigorous research has revealed that the composition of the gut microbiota is altered and the diversity of bacteria is reduced in liver diseases. Significance of various factors transported to the liver by portal vein blood flow from the intestine has been extensively investigated. Gut microbiota in liver disease can be associated with disease progression regardless of disease etiology and even with carcinogenesis. The relationship between gut microbiota and liver diseases (hepatitis virus­related diseases, autoimmune liver diseases, alcoholic liver disease, non­alcoholic fatty liver disease, non­alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) and the treatments of dysbiosis (antibiotics, prebiotics, probiotics and fecal microbiota transplantation) in liver disease are outlined based on the current evidence.

Association between Administration of Antithrombotics and Intraperitoneal Hemorrhage in Patients Undergoing Percutaneous Interventions for Liver Diseases.

Currently, percutaneous interventions are essential for diagnosis and treatment of liver diseases. The most frequent complication of percutaneous interventions is intraperitoneal hemorrhage. Recently, the number of patients with liver diseases on antithrombotics has been increasing. This retrospective cohort study aimed to evaluate the risk factors for intraperitoneal hemorrhage in patients after percutaneous interventions for liver diseases. This study included 1025 patients who underwent percutaneous interventions for liver diseases from April 2015 to March 2020. All interventions were performed using an ultrasound-guided approach. The influence of antithrombotic drug administration in patients, who underwent percutaneous interventions according to the guidelines for the American Association for the Study of Liver Disease, was evaluated. Intraperitoneal hemorrhage after percutaneous interventions was detected by computed tomography. Intraperitoneal hemorrhage occurred in nine patients (0.88%); however, these adverse events were not severe. We compared clinical characteristics between the patients with and without intraperitoneal hemorrhage. Although, there was no difference based on the administration of antithrombotics (p = 0.1961), seven of nine patients who showed intraperitoneal hemorrhage received percutaneous treatments (radio frequency ablation or microwave ablation). Therefore, we divided patients who underwent treatments and liver biopsy and then investigated the influence of antithrombotics on the intraperitoneal hemorrhage. After propensity score matching in each patient group, the administration of antithrombotics was not identified as a risk factor for hemorrhage in patients who underwent interventional treatments and patients who underwent liver biopsy. When the antithrombotics were discontinued, according to the guidelines, it may not increase the risk factor for hemorrhage in patients of liver disease who underwent percutaneous interventions.

Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir.

INTRODUCTION: Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch. METHODS: ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA <20 IU/mL). RESULTS: We analyzed 425 eligible patients (mean age 60.7 ± 13.2 years, 60% men, 90.8% Asian, 20.7% with diabetes, 27% with hypertension, 14.8% with cirrhosis, 8.3% with hepatocellular carcinoma, and mean ETV duration before switch 6.16 ± 3.17 years). The mean baseline estimated glomerular filtration rate (eGFR) was 89 ± 19 (chronic kidney disease [CKD] stages: 55.6% stage 1, 35.7% stage 2, and 8.8% stages 3-5). CVS rate increased from 91.90% at switch (from 90.46% 24 weeks before switch) to 95.57% and 97.21% at 48 and 96 weeks after (P = 0.03 and 0.02, respectively). Over the 96 weeks after switch, mean HBV DNA (P < 0.001) but not alanine aminotransferase or CKD stage decreased. Between switch and 96-week follow-up, 11% (26/235) of CKD stage 1 patients migrated to stage 2 and 8% (12/151) of stage 2 patients to stages 3-5, whereas 18% (27/151) from stage 2 to 1, and 19% (7/37) from stages 3-5 to 2. On multivariable generalized estimated equation analysis adjusted for age, sex, hypertension, diabetes, and cirrhosis, baseline eGFR, age (P < 0.001), and CKD stages 2 and 3-5 (vs 1) (both P < 0.001) were associated with lower follow-up eGFR. DISCUSSION: After an average of 6 years on ETV, CVS increased from 91.9% at TAF switch to 97.2% at 96 weeks later.

Prognostic Impact of the SARC-F Score in Gastrointestinal Advanced Cancers.

We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0-2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/µL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.

Safety and Efficacy of Laparoscopic Liver Resection for Colorectal Liver Metastasis With Obesity.

INTRODUCTION: Laparoscopic liver resection (LLR) in obese patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities. METHODS: The safety and efficacy outcomes in 314 patients who underwent laparoscopic or open nonanatomical liver resection for colorectal liver metastases (CRLM) were analyzed retrospectively with respect to the patients' body mass index (BMI) and visceral fat area (VFA). RESULTS: Two hundred and four patients underwent LLR, and 110 patients underwent open liver resection (OLR). The rate of conversion from LLR to OLR was 4.4%, with no significant difference between the BMI and VFA groups (P = .647 and .136, respectively). In addition, there were no significant differences in terms of operative time and estimated blood loss in LLR (P = .226 and .368; .772 and .489, respectively). The incidence of Clavien-Dindo grade IIIa or higher complications was not significantly different between the BMI and VFA groups of LLR (P = .877 and .726, respectively). In obese patients, the operative time and estimated blood loss were significantly shorter and lower, respectively, in LLR than in OLR (P = .003 and < .001; < .001 and < .001, respectively). There was a significant difference in the incidence of postoperative complications, organ/space surgical site infections, and postoperative bile leakage between the LLR and OLR groups (P = .017, < .001, and < .001, respectively). CONCLUSION: LLR for obese patients with CRLM can be performed safely using various surgical devices with no major difference in outcomes compared to those in nonobese patients. Moreover, LLR has better safety outcomes than OLR in obese patients.

The Effects of Allogeneic Blood Transfusion in Hepatic Resection.

BACKGROUND: Hepatectomy has a high risk of perioperative bleeding due to the underlying disease. Here, we investigated the postoperative impact of allogeneic blood transfusion during hepatectomy. METHODS: The surgical outcomes in 385 patients who underwent hepatic resection for hepatocellular carcinoma were retrospectively reviewed. The association of allogeneic blood transfusion with surgical outcomes and remnant liver regeneration data was analyzed. RESULTS: Eighty-six patients (24.0%) received an allogeneic blood transfusion and 272 patients (76.0%) did not. After propensity score matching, the incidence rates of postoperative complication (Clavien-Dindo grade >IIIA), posthepatectomy liver failure, and massive ascites were significantly higher for the group that received a blood transfusion than for the group that did not receive blood transfusion (P < .001, P = .001, and <.001, respectively). Postoperative measures of total bilirubin, albumin, platelet count, prothrombin time, aspartate aminotransferase, and alanine aminotransferase were significantly more favorable in patients without blood transfusion until day 7 after surgery. There were no correlations in the remnant liver regeneration at 7 days, and 1, 2, 5, and 12 months postoperatively between the 2 groups (P = .585, .383, .507, .261, and .430, respectively). Regarding prognosis, there was no significant difference in overall and recurrence-free survival between the 2 groups (P = .065 and .166, respectively). CONCLUSION: Allogeneic transfusion during hepatectomy strongly affected remnant liver function in the early postoperative period; however, this was not related to the remnant liver regeneration volume. Despite that the allogeneic transfusion resulted in poorer postoperative laboratory test results and increased postoperative complication and mortality rates, it had no effect on the long-term prognosis.