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Background: The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive., Methods: A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan., Results: From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002)., Conclusion: In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/Aim: The combination of bevacizumab and atezolizumab (Bev-Ate) has been established as a standard first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC) since 2020. This study examined the outcomes of HCC patients who received the combination in southern Taiwan. Patients and Methods: All patients were enrolled from four hospitals in Taiwan. They received Bev-Ate therapy for unresectable HCC. Results: Thirty-five patients were included; 28 (80%) had Barcelona Clinic Liver Cancer stage C disease. Hepatitis etiology was chronic hepatitis B and C in 63% and 17% of patients, respectively. Eleven (31%) patients had received prior systemic treatment for unresectable HCC. The response rate was 51%, and the disease control rate was 72% for all patients. The median progression-free survival (PFS) and overall survival (OS) was 5.2 and 22.2 months, respectively. For patients who received prior systemic treatment, the efficacy of Bev-Ate in terms of response rates was similar compared with those without prior systemic treatment. Patients who received lower doses of bevacizumab (<15 mg/kg per dose) had non-inferior PFS and OS compared with those receiving a standard dose of bevacizumab. The incidence of proteinuria of all grades (15.8%) was less common when lower doses of bevacizumab were used. Conclusion: Real world data from HCC patients in southern Taiwan disclosed that the efficacy outcomes of Bev-Ate treatment were generally consistent with those of clinical trials in other countries. In patients who were exposed to prior systemic treatment or who received lower doses of bevacizumab, the Bev-Ate regimen retained its clinical efficacy. [ABSTRACT FROM AUTHOR]

Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical needs still remain and require improvement in efficacy. Using murine colon carcinoma (CT26) allograft models, we examined the efficacy and elucidated novel tumor microenvironment (TME) remodeling mechanisms underlying the combination of chidamide (a benzamide-based class l histone deacetylase inhibitor; brand name in Taiwan, Kepida®) with VEGF receptor tyrosine kinase inhibitor (TKIs; cabozantinib/regorafenib, etc.) and immune checkpoint inhibitors (ICIs; anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies). The TME was assessed using flow cytometry and RNA-sequencing to determine the novel mechanisms and their correlation with therapeutic effects in mice with significant treatment response. Compared with ICI alone or cabozantinib/regorafenib + ICI, combination of chidamide + cabozantinib/regorafenib + ICI increased the tumor response and survival benefits. In particular, treatment of CT26-bearing mice with chidamide + regorafenib + anti-PD-1 antibody showed a better objective response rate (ORR) and overall survival (OS). Similar results were observed in anti-PD-1 treatment-resistant mice. After treatment with this optimal combination, in the TME, RNA-sequencing revealed that downregulated mRNAs were correlated with leukocyte migration, cell chemotaxis, and macrophage gene sets, and flow cytometry analysis showed that the cell numbers of myeloid-derived polymorphonuclear suppressor cells and tumor-associated macrophages were decreased. Accordingly, chidamide + regorafenib + anti-PD-1 antibody combination therapy could trigger a novel TME remodeling mechanism by attenuating immunosuppressive cells, and restoring T-cell activation to enhance ORR and OS. Our studies also showed that the addition of Chidamide to the regorafenib + anti-PD-1 Ab combination could induce a durable tumor-specific response by attenuating immune suppression in the TME. In addition, this result suggests that TME remodeling, mediated by epigenetic immunomodulator combined with TKI and ICI, would be more advantageous for achieving a high objective response rate, when compared to TKI plus ICI or ICI alone, and maintaining long-lasting antitumor activity. [ABSTRACT FROM AUTHOR]

Lenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%, p = 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months, p = 0.05) and OS (22.9 vs. 10.3 months, p = 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5–12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1–9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1–0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted. [ABSTRACT FROM AUTHOR]

Objectives. Whether uric acid-lowering agent use in asymptomatic hyperuricemia can reduce the development of the first gout flare remains unsettled. The goal of the present research was to test the efficacy of benzbromarone and allopurinol on primary prevention of the first gout flare in persons with asymptomatic hyperuricemia in Taiwan. Methods. One observational cohort study was constructed to examine the 2001–2015 dataset adapted from the National Health Insurance Program of Taiwan containing the claims data of 2 million beneficiaries. Asymptomatic hyperuricemia was considered as individuals on uric acid-lowering therapy who did not have gout flares. Individuals aged 20–84 without gout flares who had the use of benzbromarone alone were assigned into a benzbromarone group. Individuals ages 20–84 without gout flares who had the use of allopurinol alone were assigned into an allopurinol group. The final study included 6111 pairs of 1:1 propensity score-matched individuals from both benzbromarone and allopurinol groups. The end point was assigned as individuals who were newly diagnosed with their first gout flare. The incidence rate of the first gout flare was estimated between the benzbromarone and allopurinol groups. A Cox proportional hazards regression model was applied to explore the hazard ratio and 95% confidence interval of the first gout flare related to benzbromarone use and allopurinol use. Results. The incidence rate of the first gout flare was lower in the benzbromarone group compared with an allopurinol group (3.29 versus 5.46 per 1000 person-months, incidence rate ratio = 0.60 and 95% confidence interval = 0.56–0.64). After adjustment for co-variables, the adjusted hazard ratio of the first gout flare was 0.63 (95% confidence interval = 0.59–0.68, p < 0.001) for the benzbromarone group when compared with the allopurinol group. Conclusion. People with asymptomatic hyperuricemia taking benzbromarone have a lower hazard of developing their first gout flare when compared with those taking allopurinol. Based on the medication safety, the therapeutic effects and the low price, with oral administration once daily, we suggest that benzbromarone should be the first drug of choice if clinicians are treating asymptomatic hyperuricemia. [ABSTRACT FROM AUTHOR]

Background Spinal cord injury (SCI)-induced secondary oxidative stress associates with a clinical complication and high mortality. Treatments to improve the neurological outcome of secondary injury are considered as important issues. The objective of the current study is to evaluate the anti-oxidative effect of Tithonia diversifolia ethanolic extracts (TDE) on cells and apply the pharmacological effect to SCI model using a MRI imaging algorism. Methods The anti-oxidation properties were tested in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Rat liver cells (clone-9) were treated with various doses of TDE (0 ~ 50 μg/ml) before exposed to 250 μM H2O2 and cell survival was determined by MTT and LDH assays. We performed water apparent diffusion coefficient (ADC) map in MR techniques to investigate the efficacy of TDE treatment on SCI animal model. We performed T5 laminectomy and compression (50 g, 1 min) to induce SCI. PHILIP 3.0 T MRI was used to image 24 male Sprague-Dawley rats weighing 280-320 g. Rats were randomly divided into three groups: sham group, SCI group, SCI treated with TDE group. The MRI images were taken and ADC were acquired before and after of treatment of TDE (50 mg/kg B. W. orally, 5 days) in SCI model. Results TDE protected clone-9 cells against H2O2-induced toxicity through DPPH scavenging mechanism. In addition, SCI induced the increase in ADC after 6 hours. TDE treatment slightly decreased the ADC level after 1-week SCI compared with control animals. Conclusion Our studies have proved that the cytoprotection effect of TDE, at least in part, is through scavenging ROS to eliminate intracellular oxidative stress and highlight a potential therapeutic consideration of TDE in alternative and complementary medicine. [ABSTRACT FROM AUTHOR]

Background The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. Aim To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. Methods A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. Results Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1–16) and 5.1 (1–15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. Conclusion A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC. [ABSTRACT FROM AUTHOR]