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Simple Summary: This study explored the factors associated with treatment efficacy, treatment duration, and overall survival (OS) in 58 patients with advanced hepatocellular carcinoma undergoing atezolizumab + bevacizumab therapy. Better baseline cognitive and physical function scores and absence of severe (grade ≥ 2) hypoalbuminemia were associated with an improved objective response rate, longer treatment duration, and better OS. These findings highlight the importance of monitoring and managing treatment-related adverse events and maintaining health-related quality of life through multidisciplinary care. Background/Objectives: Health-related quality of life (HRQoL) is critical in patients with hepatocellular carcinoma (HCC). It has become a key endpoint in the evaluation of new therapies, including atezolizumab + bevacizumab (Atezo + Bev) therapy. Methods: This study explored the factors associated with treatment efficacy, treatment duration, and overall survival (OS) in patients with advanced HCC undergoing Atezo + Bev therapy. We included 58 consecutive patients with HCC receiving Atezo + Bev from 19 November 2020, to 28 December 2023, who were followed up until the end of the study or death. We analyzed the relationships between baseline characteristics, adverse events (AEs), and HRQoL and efficacy, OS, and treatment duration. Results: The demographic (older men) and baseline characteristics (Child–Pugh score of 5, Barcelona Clinic Liver Cancer Stage C) were consistent with those of previous studies. The treatment demonstrated promising efficacy with a disease control rate of 71.2%, but HRQoL scores in five functional domains and seven symptoms worsened significantly within the first 3 months. Notably, better baseline cognitive and physical function scores and absence of severe (grade ≥ 2) hypoalbuminemia were associated with an improved objective response rate, longer treatment duration, and better OS. Conclusions: These findings underscore the importance of monitoring and managing treatment-related AEs and maintaining the HRQoL. They also highlight the crucial and reassuring role of multidisciplinary care in enhancing treatment outcomes in this cohort. [ABSTRACT FROM AUTHOR]

Aim: Cell‐free and concentrated ascites reinfusion therapy (CART) and large‐volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA. Methods: From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8‐week observation period. Results: Among all patients at entry (median age, 63 years; 52% men; 60% Child–Pugh B and 40% Child–Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health‐related quality of life (HRQOL) and prominent ascites‐related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP. Conclusions: CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Aim: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III‐based therapy. Methods: This study was a retrospective, multicenter study to investigate the liver‐related events and the survival rates in 240 patients with PVT who received the therapy. Results: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver‐related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non‐responder, and PVT progression were significantly associated with liver‐related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non‐responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End‐stage Liver Disease‐Sodium score significantly contributed to 3‐year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. Conclusions: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver‐related events in antithrombin III‐based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver‐related events, but also PVT progression and improve the prognosis. [ABSTRACT FROM AUTHOR]

Background: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. Objective: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. Methods: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC was composed of the presence and absence of complications, such as variceal bleeding, hepatic ascites, and hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort and (ii) the presence and absence of complications in the patients with LC. Results: There was a significant difference among the patients without LC and those with alcohol, NAFLD-related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD-related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol-related cirrhosis unless there was a presence of G alleles. Conclusion: The PNPLA3 polymorphism was associated with the risk of NAFLD-related LC and its complications. [ABSTRACT FROM AUTHOR]

Background: Lusutrombopag effectively increases platelet count in patients with severe thrombocytopenia. However, no multicenter studies analyzing the effects of Lusutrombopag on patients with mild thrombocytopenia (platelet count > 50 000/µL) have been performed. In this study, we aimed to clarify the efficacy of Lusutrombopag on these patients by unifying background factors by propensity score matching. Methods: A total of 139 patients with thrombocytopenia were enrolled, and matched for age, sex, etiology, disease, treatment, liver function, renal function, peripheral blood count, and spleen index. The primary endpoint was to compare the increase in platelet count from baseline between the high‐platelet group (>50 000/µL) and the low‐platelet group (<50 000/µL) after Lusutrombopag treatment, using propensity score matching. The secondary endpoint was to clarify platelet transfusion avoidance rate and adverse events, moreover, to identify independent predictors associated with the increase in platelet count. Results: The mean increase in platelet count was 67 000/μL vs 48 000/μL in all patients (high‐ vs low‐platelet group, P =.024), and 64 000/μL vs 48 000/μL (P =.12) after propensity score matching. The increase in platelet count and the platelet transfusion avoidance rate tended to be higher in the high‐platelet group. There was no significant difference between adverse events. Predictors associated with an increase in platelet count were sex, estimated glomerular filtration rate, and spleen index by multivariate analysis. Conclusion: Lusutrombopag has a little stronger effect in patients with mild thrombocytopenia than those with severe thrombocytopenia and showed a more substantial effect in patients with impaired renal function and small spleen. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u‐HCC). Method: Ninety‐four u‐HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child‐Pugh (CP)‐A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B‐IMbrave150‐in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP‐B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B‐IMbrave150‐out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. Results: The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP‐B than CP‐A patients (p = 0.030). Objective response (OR) rates of the B‐IMbrave150‐in group (28.3%, 39.1%) were significantly higher than those of the B‐IMbrave150‐out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B‐IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST. Conclusion: In real‐world practice, ATZ + BV treatment might offer significant benefits in patients who meet B‐IMbrave150 criteria or have low NLR. [ABSTRACT FROM AUTHOR]

Background: To make an accurate estimate of the response to thrombopoietin (TPO) receptor agonists for thrombocytopenia associated with chronic liver disease, we evaluated the influence of antiplatelet autoantibodies on the response to lusutrombopag in thrombocytopenic patients with liver disease. Methods: A prospective study was conducted at 2 hospitals. Thrombocytopenic patients with liver disease received oral lusutrombopag 3.0 mg once daily for up to 7 days. We analyzed changes in platelet counts from baseline to the maximum platelet count on days 9–14. The definition of clinical response was a platelet count of ≥5 × 104/μL with an increased platelet count of ≥2 × 104/μL from baseline. We assessed the correlation between the response to treatment drug and antiplatelet autoantibodies measured by anti-GPIIb/IIIa antibody-producing B cells. Results: Thirty patients received the trial drug. There were 25 responders and 5 nonresponders. The median change in platelet counts was 3.9 × 104/μL (95% CI 2.8–4.6, p < 0.0001). The correlation between change in platelet counts and the frequency of the anti-glycoprotein IIb/IIIa antibody-producing B cells was moderate (r = 0.414, 95% CI 0.064–0.674, p = 0.023). In multivariate analysis of factors affecting the change in platelet counts, the anti-GPIIb/IIIa antibody-producing B cells were identified as an independent factor (regression coefficient [B] = 0.089; CI 0.021–0.157, p = 0.013). Conclusion: Anti-GPIIb/IIIa antibody-producing B cells may be a predictor for TPO receptor agonists in patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Background: We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. Methods: We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. Results: Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, p = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; p = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. Conclusions: The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH. [ABSTRACT FROM AUTHOR]

A 71‐year‐old man was diagnosed with B‐cell chronic lymphocytic leukemia. He was negative for hepatitis B surface antigen (HBsAg), positive for antibodies against the hepatitis B surface and core, and negative for hepatitis B virus (HBV)‐DNA before starting chemotherapy. A total of 13 months after the initiation of ibrutinib (a Bruton's tyrosine kinase inhibitor), the patient's alanine aminotransferase levels suddenly increased to 427 U/L. As the level of serum HBV‐DNA increased to 5.2 logIU/mL, a diagnosis of HBV reactivation was made, whereas the patient remained negative for HBsAg. The patient's serum alanine aminotransferase levels normalized after the initiation of entecavir at a dose of 1 mg/day. However, it took >1 year to achieve an undetectable level of HBV‐DNA, even with an add‐on therapy of tenofovir disoproxil fumarate. Interestingly, the patient remained negative for HBsAg throughout the clinical course owing to triple HBsAg escape mutations: Q101K, M133L, and G145A. [ABSTRACT FROM AUTHOR]