Impact of the COVID-19 pandemic on the treatment of acute cholangitis caused by choledocholithiasis: A single-center retrospective study in Japan.

Objectives: This study aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis. Methods: The Japanese government declared a state of emergency in April 2020 due to the COVID-19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022. Results: Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0-1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single-stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups. Conclusions: Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID-19 pandemic resulted in an increase in the number of single-stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis.

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21-3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.

Prognostic Factors for Severe-to-Fatal Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicenter Prospective Cohort Study.

The prognostic factors associated with severe-to-fatal post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain unclear despite the extensive number of studies on PEP. In total, 3739 ERCP patients with biliary disease with an intact papilla and indicated for ERCP were prospectively enrolled at 36 centers from April 2017 to March 2018. Those with acute pancreatitis diagnosed before ERCP, altered gastrointestinal anatomy, and an American Society of Anesthesiologists (ASA) physical status > 4 were excluded. Univariate and multivariate logistic regression analyses were performed on patient-related factors, operator-related factors, procedure-related factors, and preventive measures to identify potential prognostic factors for severe-to-fatal PEP. Multivariate analyses revealed pancreatic guidewire-assisted biliary cannulation (OR 13.59, 95% CI 4.21-43.83, p < 0.001), post-ERCP non-steroidal anti-inflammatory drug (NSAID) administration (OR 11.54, 95% CI 3.83-34.81, p < 0.001), and previous pancreatitis (OR 6.94, 95% CI 1.45-33.33, p = 0.015) as significant risk factors for severe-to-fatal PEP. Preventive measures included endoscopic biliary sphincterotomy (EST; OR 0.29, 95% CI, 0.11-0.79, p = 0.015) and prophylactic pancreatic stents (PPSs; OR 0.11, 95% CI, 0.01-0.87, p = 0.036). In biliary ERCP, pancreatic guidewire-assisted biliary cannulation, NSAID administration after ERCP, and previous pancreatitis were risk factors for severe-to-fatal PEP, whereas EST and PPS were significant preventive measures for severe-to-fatal PEP.

VWF/ADAMTS13 Ratio as a Potential Predictive Biomarker for Acute Kidney Injury Onset in Cirrhosis.

AIM: We investigated the von Willebrand factor to ADAMTS13 ratio (von Willebrand factor [VWF]:Ag/ADAMTS13:AC) as a potential biomarker for the outcomes of acute kidney injury (AKI) in liver cirrhosis (LC). METHODS: This retrospective cross-sectional study included patients with LC who developed AKI (AKI group: n = 91) and patients with LC who did not develop AKI [non-AKI (NAKI) group, n = 91] as a control group. Plasma levels of the von Willebrand factor antigen (Ag) and ADAMTS13 activity (AC) were measured in patients with AKI or NAKI. Moreover, risk factors for onset of AKI, AKI-associated 90-day mortality, and poor AKI treatment response were identified. RESULTS: The AKI group had a significantly higher VWF:Ag/ADAMTS13:AC than the NAKI group. Values of VWF:Ag/ADAMTS13:AC ≥ 5.7 were identified as risk factors for AKI onset in patients with LC (odds ratio [OR] 2.56; 95% CI 1.26-4.99; p < 0.001). Among patients with AKI, values of VWF:Ag/ADAMTS13:AC ≥ 9.0 were identified as risk factors for 90-day mortality (OR 6.83; 95% CI 2.32-20.10; p < 0.001). Cumulative survival was significantly lower in those with high (≥ 9.0) than in those with low (< 9.0) VWF:Ag/ADAMTS13:AC. Furthermore, values of VWF:Ag/ADAMTS13:AC ≥ 7.4 were identified as risk factors for poor treatment response (OR 4.2; 95% CI 1.39-12.70; p < 0.001). The treatment response rates were significantly higher in those with low (< 7.4) VWF:Ag/ADAMTS13:AC than in those with high (≥ 7.4) VWF:Ag/ADAMTS13:AC. CONCLUSION: VWF:Ag/ADAMTS13:AC potentially predicts the onset, prognosis, and treatment response of AKI in patients with LC.

Complete migration of a fully covered self-expandable metallic stent after endoscopic ultrasound-guided hepaticogastrostomy: A case report.

A male patient underwent gastrojejunal bypass surgery in 2017. In 2020, he was referred to our hospital for suspected obstructive jaundice. Subsequently, he was diagnosed with cholangiocarcinoma, and endoscopic retrograde cholangiopancreatography was attempted via balloon-assisted enteroscopy. However, the endoscope did not reach the duodenal papilla owing to the abdomen-small intestine adhesion. Therefore, endoscopic ultrasound-guided hepaticogastrostomy was performed using a dedicated plastic stent. After stent placement, obstructive jaundice and cholangitis promptly improved. However, we replaced the plastic stent with a fully covered self-expandable metal stent because stent occlusions occurred frequently. Two months after fully covered self-expandable metal stent placement, the patient developed cholangitis again. Notably, during the endoscopic procedure, the stent was found to be completely migrated. Nevertheless, the fistula was still open, and the patient was successfully retreated with the maintained fistula of endoscopic ultrasound-guided hepaticogastrostomy.

Hemoglobin and Endotoxin Levels Predict Sarcopenia Occurrence in Patients with Alcoholic Cirrhosis.

Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance.

Hemoglobin levels as a surrogate marker of sarcopenia in patients with liver cirrhosis.

AIM: This study aimed to elucidate a surrogate marker of sarcopenia in patients with liver cirrhosis (LC). METHODS: A total of 424 patients were assessed for handgrip strength (HGS) and skeletal muscle index (SMI). They were divided into two groups: sarcopenia (Group S; n = 80) and nonsarcopenia (Group NS; n = 344). RESULTS: Group S showed significantly lower HGS, SMI, and hemoglobin (Hb) levels in males and female patients, and lower serum levels of albumin, cholinesterase, and zinc (all p < 0.001), along with significantly higher serum levels of procollagen type III-N-peptide and type IV collagen 7S-domain (p < 0.001 and p < 0.0017) than Group NS. The risk factors for sarcopenia were age 65 years or older, female gender, Child-Pugh class C, and Hb levels <10.9 g/dL in women and <12.4 g/dL in men (p = 0.012, p < 0.001, p = 0.031, and p < 0.001, respectively). Significant positive correlations were found between the Hb level and the SMI and HGS (r = 0.4, p < 0.001 and r = 0.4, p < 0.001, respectively). Sarcopenia, low HGS, and low SMI were significantly associated with overall survival in patients with LC (all p < 0.001). The predictive accuracy of Hb levels for predicting sarcopenia was significantly higher than for predicting SMI and tended to be higher than for predicting HGS (p = 0.014 and p = 0.059, respectively). CONCLUSION: Hemoglobin levels are predictive of sarcopenia in patients with LC and warrants further investigation as a biomarker for sarcopenia in LC.

Changes in Coagulation and Fibrinolytic Factors in Patients With Cirrhotic Refractory Ascites Undergoing Cell-free and Concentrated Ascites Reinfusion Therapy: A Retrospective Observational Study in Japan.

BACKGROUND/AIM: The management of refractory ascites is critical for the treatment of patients with decompensated cirrhosis. This study aimed to evaluate the feasibility and safety of cell-free and concentrated ascites reinfusion therapy (CART) in patients with cirrhosis and refractory ascites, with a focus on changes in coagulation and fibrinolytic factors in ascitic fluid following CART. PATIENTS AND METHODS: This was a retrospective cohort study including 23 patients with refractory ascites undergoing CART. Serum endotoxin activity (EA) before and after CART and the levels of coagulation and fibrinolytic factors and proinflammatory cytokines in original and processed ascitic fluid were measured. The Ascites Symptom Inventory-7 (ASI-7) scale was used for subjective symptom assessment before and after CART. RESULTS: Body weight and waist circumference significantly decreased after CART, whereas serum EA did not significantly change after CART. Similar to the previous reports, ascitic fluid concentrations of total protein, albumin, high-density lipoprotein cholesterol, γ-globulin, and immunoglobulin G levels were significantly increased after CART; mild elevations in body temperature and interleukin 6 and tumor necrosis factor-alpha levels in ascitic fluid were also observed. Importantly, the levels of antithrombin-III, factor VII, and X, which are useful for patients with decompensated cirrhosis, were markedly increased in the reinfused fluid during CART. Finally, the total ASI-7 score was significantly lower following CART, compared with the pre-CART score. CONCLUSION: CART is an effective and safe approach for the treatment of refractory ascites that allows the intravenous reinfusion of coagulation and fibrinolytic factors in the filtered and concentrated ascites.

Sulforaphane Potentiates Gemcitabine-Mediated Anti-Cancer Effects against Intrahepatic Cholangiocarcinoma by Inhibiting HDAC Activity.

Intrahepatic cholangiocarcinoma (iCCA), the second most common primary liver cancer, has high mortality rates because of its limited treatment options and acquired resistance to chemotherapy. Sulforaphane (SFN), a naturally occurring organosulfur compound found in cruciferous vegetables, exhibits multiple therapeutic properties, such as histone deacetylase (HDAC) inhibition and anti-cancer effects. This study assessed the effects of the combination of SFN and gemcitabine (GEM) on human iCCA cell growth. HuCCT-1 and HuH28 cells, representing moderately differentiated and undifferentiated iCCA, respectively, were treated with SFN and/or GEM. SFN concentration dependently reduced total HDAC activity and promoted total histone H3 acetylation in both iCCA cell lines. SFN synergistically augmented the GEM-mediated attenuation of cell viability and proliferation by inducing G2/M cell cycle arrest and apoptosis in both cell lines, as indicated by the cleavage of caspase-3. SFN also inhibited cancer cell invasion and decreased the expression of pro-angiogenic markers (VEGFA, VEGFR2, HIF-1α, and eNOS) in both iCCA cell lines. Notably, SFN effectively inhibited the GEM-mediated induction of epithelial-mesenchymal transition (EMT). A xenograft assay demonstrated that SFN and GEM substantially attenuated human iCCA cell-derived tumor growth with decreased Ki67+ proliferative cells and increased TUNEL+ apoptotic cells. The anti-cancer effects of every single agent were markedly augmented by concomitant use. Consistent with the results of in vitro cell cycle analysis, G2/M arrest was indicated by increased p21 and p-Chk2 expression and decreased p-Cdc25C expression in the tumors of SFN- and GEM-treated mice. Moreover, treatment with SFN inhibited CD34-positive neovascularization with decreased VEGF expression and GEM-induced EMT in iCCA-derived xenografted tumors. In conclusion, these results suggest that combination therapy with SFN with GEM is a potential novel option for iCCA treatment.

Does endoscopic sphincterotomy contribute to the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis after endoscopic biliary stenting for malignant biliary obstruction? A multicenter prospective cohort study.

BACKGROUND: There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study. METHODS: We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients. RESULTS: Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES. CONCLUSION: Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.

Gastrojejunostomy versus endoscopic duodenal stent placement for gastric outlet obstruction in patients with unresectable pancreatic cancer: a propensity score-matched analysis.

BACKGROUND: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC. METHODS: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching. RESULTS: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group. CONCLUSION: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy.

Diagnostic yield of liquid-based cytology in serial pancreatic juice aspiration cytological examination.

Objectives: Serial pancreatic juice aspiration cytological examination (SPACE) via endoscopic retrograde cholangiopancreatography is a useful diagnostic method for early-stage pancreatic cancer, such as carcinoma in situ that are difficult to diagnose by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, the diagnostic accuracy of SPACE is low, which is attributed to problems regarding specimen treatment. Hence, we evaluated the diagnostic efficacy of liquid-based cytology (LBC) in pancreatic juice cytology for pancreatic cancer. Methods: We retrospectively analyzed 24 patients with suspected pancreatic cancer that was difficult to diagnose by endoscopic ultrasound-guided fine needle aspiration who underwent SPACE using LBC between April 2017 and April 2021. Results: The most common reason for performing SPACE was localized stenosis of the main pancreatic duct without a mass. Eleven patients were diagnosed with malignancy after surgical resection, nine of whom had pancreatic ductal adenocarcinoma. Ten patients were diagnosed as benign after a follow-up of more than 1 year. The nine cases of malignancy were diagnosed before surgical resection by SPACE using LBC, with a sensitivity of 81.8% and specificity of 100%. The overall diagnostic accuracy was 91.7%. A total of 152 LBC examinations were performed via SPACE, with an adequate sample collection rate of 88.9%. No adverse events, including acute pancreatitis, occurred after endoscopic retrograde cholangiopancreatography. Conclusion: SPACE with LBC offers good diagnostic efficacy in patients with pancreatic cancer that is difficult to diagnose by endoscopic ultrasound-guided fine needle aspiration.

Efficacy of a dedicated plastic stent in endoscopic ultrasound-guided hepaticogastrostomy during the learning curve: cumulative multi-center experience.

BACKGROUND AND OBJECTIVES: Currently, there are no reports on the learning curve of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using dedicated plastic stents. Therefore, we evaluated the outcomes of EUS-HGS using dedicated plastic stents at tertiary referral centers during the initial development phase of EUS-HGS. MATERIALS AND METHODS: Endoscopic retrograde cholangiopancreatography (ERCP) was strictly prioritized over EUS-HGS. Twenty-three consecutive patients treated using EUS-HGS with a 7-Fr dedicated plastic stent over 4 years beginning in 2018 were analyzed retrospectively. RESULTS: The most common primary disease was pancreatic cancer, and the most common reason for difficulty in ERCP was duodenal obstruction, followed by surgically altered anatomy. The overall technical success rate of EUS-HGS was 95.7% (22/23). One failed case was converted to EUS-guided choledochoduodenostomy. The clinical success rate was 90.9% (20/22). Adverse events (AEs) related to the procedure were observed in four (17.4%) patients, including mild biliary peritonitis in three (13.0%) and mild cholangitis in one (4.3%) patient; all patients received conservative therapy. No serious AEs, such as stent migration, bleeding, or gastrointestinal perforation, were observed. Recurrent biliary obstruction (RBO) was observed in eight (34.8%) patients. Of these, HGS stent replacement was performed in four patients, and other treatments were performed in the remaining four patients. Another four (17.4%) patients did not develop RBO but underwent periodic HGS stent replacement. CONCLUSIONS: EUS-HGS using a dedicated plastic stent was performed safely even in its initial phase of introduction. The approach using this stent can be useful in case of ERCP failure for biliary decompression because of the high feasibility and low risk of serious adverse events.

Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.

BACKGROUND/AIM: To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib. PATIENTS AND METHODS: Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels. RESULTS: Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108). CONCLUSION: Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Initial Experience With Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma: A Real-world Retrospective Study.

BACKGROUND/AIM: The current study evaluated the efficacy and toxicity of atezolizumab plus bevacizumab in patients with advanced-stage hepatocellular carcinoma in a real-world setting. PATIENTS AND METHODS: This retrospective study enrolled 23 patients. The primary endpoint was progression-free survival (PFS). Antitumor responses 6 weeks after initiation of atezolizumab plus bevacizumab were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and the modified RECIST (mRECIST). The Common Terminology Criteria for Adverse Events version 5.0 was used to evaluate the severity of adverse events. Relative changes in hepatic function and nutritional status were investigated. RESULTS: The median PFS was 119 days. The objective response rate (ORR) and disease control rate (DCR) at 6 weeks based on RECIST were 21.7% and 60.9%, respectively. The ORR and DCR based on mRECIST were 26.1% and 69.6%, respectively. The group with hepatitis B/C-related HCC had a higher ORR based on mRECIST than the non-hepatitis B and C-related group. Patients with Barcelona Clinic Liver Cancer (BCLC) stage A and B disease had a higher DCR based on RECIST than those with BCLC stage C disease. The incidence rates of any grade and grade ≥3 adverse events were 65.2% and 21.7%, respectively. The albumin-bilirubin and Child-Pugh scores, neutrophil-to-lymphocyte ratio and skeletal muscle index did not significantly worsen within 6 weeks after treatment initiation. CONCLUSION: Atezolizumab plus bevacizumab is effective and safe and can help achieve complete remission in patients with advanced-stage hepatocellular carcinoma in a real-world setting. Nevertheless, large-scale studies must be conducted to validate its outcomes in this patient group.

Macrophage Activation Markers Predict Liver-Related Complications in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease stage, although patients with more advanced stages generally have more symptoms. It is important to develop biomarkers in order to identify patients with an increased risk of complications and end-stage liver disease. This study investigated surrogate markers for risk estimation of PBC-related complications, including a study population of 77 patients with PBC who underwent liver biopsy and were measured for serum levels of macrophage activation markers, soluble CD163 (sCD163), soluble mannose receptor (sMR), and zonulin. Patients with PBC were divided into symptomatic (Group S, n = 20) and asymptomatic (Group A, n = 57) groups. The correlations of histological stages based on both Scheuer and Nakanuma classifications with the three serum markers were investigated. The Nakanuma classification involves grading for liver fibrosis and bile duct loss. The three biomarkers were assessed for their diagnostic ability to identify patients with PBC having high risk of developing complications. The predictive factors of these complications were examined as well. Group S had significantly higher serum sMR (p = 0.011) and sCD163 (p = 0.048) levels versus Group A. A composite index of sMR and sCD163 measurements had significantly better prediction performance than sCD163 alone (p = 0.012), although not when compared to sMR alone (p = 0.129). Serum sMR was an independent factor for developing complications on both univariate (Odds ratio (OR) = 30.20, 95% confidence interval (95% CI): 3.410−267.0, p = 0.00220), and multivariate (OR = 33.70, 95% CI: 3.6600−311.0, p = 0.0019) analyses. Patients with PBC having sMR of ≥56.6 had a higher incidence of clinical complications versus those with a sMR of <56.6. Serum sMR predicts the development of complications in patients with PBC. sMR plus sCD163 showed better predictive power than either marker alone, although the addition of sCD163 did not improve the predictive power of sMR. Future prospective studies are required in order to validate the findings of the present study.