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Liver fibrosis affects approximately 800 million patients worldwide, with over 2 million deaths each year. Nevertheless, there are no approved medications for treating liver fibrosis. In this study, we investigated the impacts of ginkgetin on liver fibrosis and the underlying mechanisms. The impacts of ginkgetin on liver fibrosis were assessed in mouse models induced by thioacetamide or bile duct ligation. Experiments on human LX-2 cells and primary mouse hepatic stellate cells (HSCs) were performed to explore the underlying mechanisms, which were also validated in the mouse models. Ginkgetin significantly decreased hepatic extracellular matrix deposition and HSC activation in the fibrotic models induced by thioacetamide (TAA) and bile duct ligation (BDL). Beneficial effects also existed in inhibiting hepatic inflammation and improving liver function. In vitro experiments showed that ginkgetin markedly inhibited HSC viability and induced HSC apoptosis dose-dependently. Mechanistic studies revealed that the antifibrotic effects of ginkgetin depend on STAT1 activation, as the effects were abolished in vitro after STAT1 silencing and in vivo after inhibiting STAT1 activation by fludarabine. Moreover, we observed a meaningful cross-talk between HSCs and hepatocytes, in which IL-6, released by ginkgetin-induced apoptotic HSCs, enhanced hepatocyte proliferation by activating STAT3 signaling. Ginkgetin exhibits antifibrotic effects by inducing HSC apoptosis via STAT1 activation and enhances hepatocyte proliferation secondary to HSC apoptosis via the IL-6/STAT3 pathway.
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Biflavonoides , Células Estrelladas Hepáticas , Tioacetamida , Ratones , Animales , Humanos , Tioacetamida/metabolismo , Tioacetamida/farmacología , Tioacetamida/uso terapéutico , Interleucina-6/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Modelos Animales de Enfermedad , Apoptosis , Hígado/metabolismo , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/farmacologíaRESUMEN
To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who underwent TIPS creation. Computed tomography-based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months after TIPS creation. Multivariate logistic regression analysis was used to identify independent risk factors, which showed a significant increase in 6-month post-TIPS SMI compared with that at baseline in both men and women (for both, P < .001). Pre-TIPS SMI (odds ratio [OR], 0.93; 95% CI, 0.87-0.99; P = .031) and change in portal pressure gradient (OR, 1.13; 95% CI, 1.03-1.24; P = .009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.
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Derivación Portosistémica Intrahepática Transyugular , Sarcopenia , Masculino , Humanos , Femenino , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIMS: To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd-Chiari syndrome (BCS). METHODS: From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels. RESULTS: The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm3 vs. 771.36 ± 277.45 cm3 , p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment. CONCLUSIONS: BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.
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BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver disease. We explored simple and effective ways to improve NAFLD and investigate the mechanism of action. METHODS: NAFLD was induced in 40 rats fed a high-fat diet (HFD). Magnetic resonance imaging was used to evaluate the progression and improvement of NAFLD. The treatment-related interventions included aerobic exercise (E) and vitamin E (VE) supplementation. Expression levels of proteins related to fat metabolism were also assessed. The activities of antioxidant enzymes in the liver and serum lipid metabolism were analyzed using biochemical methods. RESULTS: Aerobic exercise and vitamin E effectively improved NAFLD in rats, resulting in decreased hepatic fat accumulation, reduced hepatocyte ballooning, and decreased triglyceride levels. Combination therapy achieved the best effect. Both aerobic exercise and vitamin E activate the AMPK pathway to phosphorylate acetyl-CoA carboxylase (ACC) and reduce fatty acid synthesis. The expression of sterol regulatory element-binding protein-1 (SREBP-1) was decreased significantly in the treated groups, particularly in the E + VE + HFD group. The expression of carnitine palmitoyl-transferase 1C (CPT1C) significantly increased in the treated groups, particularly in the E + VE + HFD group. Compared with the control group, reactive oxygen species (ROS) in the E + HFD group were slightly decreased, while that in the VE + HFD group were significantly decreased, with the even greater reduction observed in the E + VE + HFD group. CONCLUSION: Aerobic exercise and vitamin E supplementation can improve HFD-induced NAFLD in rats by regulating the AMPK pathway and reducing oxidative stress.
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Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Dieta Alta en Grasa/efectos adversos , Vitamina E/farmacología , Hígado/metabolismo , Metabolismo de los Lípidos , Estrés Oxidativo , Ratones Endogámicos C57BLRESUMEN
PURPOSE: To assess and compare the value of psoas muscle thickness at the level of the third lumbar (L3) vertebra (TPML) or umbilicus (TPMU) and skeletal muscle index (SMI) for diagnosing sarcopenia and predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: Two hundred forty-nine patients undergoing TIPS were included in this retrospective study. The cut-offs of L3-SMI for sarcopenia were 42.0 cm2/m2 in men and 38.0 cm2/m2 in women. The cut-offs for TPML/height and TPMU/height to predict mortality was established using a receiver-operating characteristic analysis. The Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Compared with TPMU/height, TPML/height was more consistent with L3-SM for the diagnosis of sarcopenia (Kappa coefficient: 0.63 vs. 0.36 in men; 0.61 vs. 0.45 in women). The Cox analysis showed that both TPML/height and TPMU/height were independent risk factors for mortality. The optimal cut-off values of TPML/height and TPMU/height for mortality in men and women were 11.2 mm/m, 9.4 mm/m, 18.4 mm/m, 15.1 mm/m, respectively. There were 119 (47.8%), 87 (34.9%), and 82 (32.9%) patients diagnosed with sarcopenia in the TPMU/height, TPML/height, and L3-SMI models, respectively. Kaplan-Meier analysis showed that the overall survival was significantly lower in the sarcopenia group in all three models. CONCLUSION: TPMU/height and TPML/height have a similar survival prognostic value as L3-SMI. TPML/height has better consistency with L3-SMI in diagnosing sarcopenia and is a more stable alternative to L3-SMI for diagnosing sarcopenia in patients undergoing TIPS.
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Derivación Portosistémica Intrahepática Transyugular , Sarcopenia , Masculino , Humanos , Femenino , Sarcopenia/diagnóstico por imagen , Músculos Psoas/diagnóstico por imagen , Cirrosis Hepática/complicaciones , Estudios Retrospectivos , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Músculo Esquelético , PronósticoRESUMEN
Background Sarcopenia is frequently found in patients with cirrhosis and is associated with liver dysfunction, cirrhosis-related complications, and poorer quality of life. Purpose To evaluate changes in skeletal muscle and fat mass at CT and to evaluate the relationship of sarcopenia to mortality in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods Patients who underwent TIPS between August 2016 and May 2020 were included in this retrospective study. Skeletal muscle and fat mass were evaluated at CT at the L3 vertebra at baseline and at 2 months, 5 months, and 1 year after TIPS. Sarcopenia was defined as L3 skeletal muscle index (SMI) less than 50 cm2/m2 for men and less than 39 cm2/m2 for women. The primary end point was change in skeletal muscle and fat mass, and secondary end points included survival and the predictive factors for survival. Changes in skeletal muscle and fat mass over time were analyzed by generalized estimating equations. Results A total of 224 patients (159 men [113 with and 46 without sarcopenia] and 65 women [32 with and 33 without sarcopenia]) were included. In male patients with sarcopenia, the mean L3 SMI increased from 41.8 cm2/m2 (baseline) to 49.1 cm2/m2 (at 5-month follow-up; P < .001) and 49.6 cm2/m2 (at 1-year follow-up; P < .001) after TIPS. In female patients with sarcopenia, SMI increased from 33.7 cm2/m2 (at baseline) to 40.6 cm2/m2 (at 5-month follow-up; P < .001) and 42.0 cm2/m2 (at 1-year follow-up; P < .001) after TIPS. Sarcopenia (hazard ratio, 3.0; 95% CI: 1.2, 7.8) was identified as an independent risk factor for mortality after TIPS, and the patients who converted from sarcopenic to nonsarcopenic had higher cumulative survival rate than those who did not (96.4% vs 82.1%; log-rank P = .04). Conclusion In patients with sarcopenia, both skeletal muscle and fat mass increased after transjugular intrahepatic portosystemic shunt placement. The reversal of sarcopenia could reduce the risk of death. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee in this issue.
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Derivación Portosistémica Intrahepática Transyugular , Sarcopenia , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Masculino , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Calidad de Vida , Estudios Retrospectivos , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagenRESUMEN
BACKGROUND: The management of type II endoleaks (T2ELs) remains controversial in current literature. Hence, this study aimed to explore the natural history of isolated type II endoleak after endovascular aneurysm repair (EVAR) and its influence on long-term outcomes based on a 10-year follow-up at a tertiary medical center. METHODS: From January 2011 to April 2021, consecutive patients who underwent elective EVAR were reviewed. The demographics, clinical characteristics, treatment details, imaging information, in the event of T2ELs, and outcomes were extracted. RESULTS: A total of 287 patients were included for analysis. Isolated T2EL was identified in 79 patients (27.5%), while no endoleak was found in 208 patients (72.5%). The mean age at EVAR was 68.1 ± 8.9 years (range, 41-92 years) and the majority of patients were male (81.5%). The mean follow-up duration was 42.7 months (range, 2-119.7 months). Among the 79 patients with isolated T2ELs, 33 (41.8%, 33/79) were early and 46 (58.2%, 46/79) were late. Spontaneous resolution of T2ELs was identified in 29 patients (36.7%, 29/79). Persistent T2ELs were observed in 50 patients (63.3%, 50/79). No sac growth was seen in 33 patients (66%, 33/50) and these patients were managed conservatively. The remaining 17 patients (34%, 17/50) showed significant sac growth. Six of them declined intervention due to various reasons and the remaining 11 patients underwent interventional embolization for T2ELs. Following the embolization, 2 patients had complete resolution of T2ELs and 9 patients had persistent T2ELs. Among the patients with persistent T2ELs, 2 patients (2/9) still showed progressive sac growth, and one of them died from aneurysm rupture; the remaining 7 patients (7/9) showed no sac growth. Patients with isolated T2ELs had a higher incidence of sac growth than patients without any endoleak (21.5% vs 4.3%, p < 0.001), while no difference was found in overall survival between the two groups. In Cox regression analysis, only higher age was independently associated with worse survival. CONCLUSIONS: Type II Endoleak was significantly associated with aneurysm sac growth and no association with survival was observed.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Endofuga/diagnóstico por imagen , Endofuga/etiología , Endofuga/terapia , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the safety and efficacy of thoracic endovascular aortic repair (TEVAR) for retrograde type A intramural hematoma (IMH) with intimal disruption in the descending aorta and report our endovascular therapeutic experience. MATERIALS AND METHODS: From January 2014 to October 2020, a total of 24 consecutive patients with retrograde type A IMH with intimal disruption (intimal tear or ulcer-like projection) in the descending aorta underwent TEVAR. The demographics, clinical characteristics, treatment details, imaging information, and follow-up results were reviewed. RESULTS: Among all patients with retrograde type A IMH, 13 (54.2%) patients presented with ulcer-like projection and 11 (45.8%) with intimal tear (aortic dissection) in the descending aorta. Successful TEVAR was achieved in all patients. There was no 30-day mortality. During a mean follow-up of 37.5 months, 1 patient (4.2%) developed permanent paralysis, 1 patient (4.2%) underwent reintervention due to the expansion of the aorta distal to the stent resulting from the enlargement of distal intimal tear at the 2 month follow up, and no other adverse events were observed. The latest computed tomographic angiography images showed that the maximum diameter of the ascending aorta and descending aorta significantly decreased after TEVAR (both p<0.001), and the IMH/false lumen in the ascending aorta and the descending thoracic aorta were completely absorbed. CONCLUSION: Thoracic endovascular aortic repair for selected patients with retrograde type A intramural hematoma that presented with intimal disruption in the descending aorta is feasible and efficient, but close surveillance is needed to manage aortic-related adverse events.
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Aneurisma de la Aorta Torácica , Procedimientos Endovasculares , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/etiología , Aneurisma de la Aorta Torácica/cirugía , Procedimientos Endovasculares/efectos adversos , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/cirugía , Humanos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Úlcera/diagnóstico por imagen , Úlcera/cirugíaRESUMEN
BACKGROUND: Sinistral portal hypertension (SPH) is a rare clinical syndrome. The purpose of this study was to assess the clinical outcomes and safety of splenic artery embolization (SAE) in the treatment of SPH. METHODS: This retrospective study included 39 SPH patients who underwent SAE treatment between August 2009 and May 2021. The cases had esophageal, gastric, or ectopic varices detected by endoscopy or enhanced CT, with symptoms or signs of upper gastrointestinal (GI) bleeding and/or postprandial fullness. Clinical symptom improvement rate, complications, and symptomatic recurrence rate were observed and analyzed after treatment. RESULTS: All the procedures were performed successfully. Of all patients, 17 received the 2-step complete SAE procedure, 19 received only the first step of the 2-step protocol (i.e., partial splenic embolization [PSE] procedure), and the remaining three received the 1-step complete SAE procedure. After the procedures, the symptoms completely disappeared in all patients, and the main complications were post-embolization syndromes, with 27 patients (69.2%) developing a low-grade fever, 24 (61.5%) developing abdominal pain and 4 (10.3%) developing nausea or mild vomiting. During the prolonged follow-up, varicose veins were gradually reduced as detected by enhanced CT; liver function parameters and platelet count remained in the normal range. Only one patient who underwent PSE treatment developed upper GI rebleeding 7 months after the procedure. CONCLUSION: Two-step complete SAE is a safe and feasible procedure for the treatment of symptomatic SPH.
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Embolización Terapéutica , Várices Esofágicas y Gástricas , Hipertensión Portal , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Várices Esofágicas y Gástricas/complicaciones , Hemorragia Gastrointestinal/etiología , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Estudios Retrospectivos , Arteria Esplénica , Vena EsplénicaRESUMEN
BACKGROUND. Various prognostic scores for patients with chronic liver disease have been applied for predicting survival after TIPS placement. In 2021, the Freiburg index of post-TIPS survival (FIPS) score was developed specifically for predicting survival after TIPS placement. The score has exhibited variable performance in initial investigations conducted in German and U.S. cohorts. OBJECTIVE. The purpose of this study was to compare the utility of the FIPS score and traditional scoring systems for predicting post-TIPS survival in a cohort of Chinese patients with cirrhosis. METHODS. This retrospective validation study compared four prognostic scores (model for end-stage liver disease [MELD], sodium MELD [MELD-Na], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD], and FIPS) in 383 patients (mean age, 54.9 ± 11.7 years; 249 men, 134 women) with cirrhosis who underwent TIPS placement (341 for variceal bleeding, 42 for refractory ascites) at Wuhan Union Hospital between January 2016 and August 2021. Model performance was assessed in terms of discrimination (using concordance index) and calibration (using Brier score and observed-to-predicted ratios) for 6-, 12-, and 24-month post-TIPS survival. Discrimination was further stratified by TIPS indication. Risk stratification was performed using previously proposed cutoffs for each score. RESULTS. During postprocedural follow-up, 72 (18.8%) patients died. Discriminative performance for 6-month survival was highest for FIPS score (concordance index, 0.784), followed by CLIF-C AD (0.743), MELD-Na (0.699), and MELD (0.694). FIPS score also showed the highest calibration in terms of lower Brier scores and observed-to-predicted ratios closer to 1 and showed the strongest prognostic performance for 12- and 24-month survival and in subgroups of patients who underwent TIPS placement for either variceal bleeding or refractory ascites (except for similar performance of FIPS and CLIF-C AD in the refractory ascites subgroup). When prior cutoffs were applied, further application of FIPS score was significantly associated with survival among patients classified as low risk by the other scores. CONCLUSION. FIPS score outperformed traditional risk scores in predicting post-TIPS survival in patients with cirrhosis. CLINICAL IMPACT. The findings support utility of FIPS score in differentiating patients who are optimal candidates for TIPS placement versus those at high risk who may instead warrant close monitoring and early liver transplant.
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Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Adulto , Anciano , Ascitis , China/epidemiología , Várices Esofágicas y Gástricas/complicaciones , Femenino , Hemorragia Gastrointestinal , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Targeted puncture of an appropriate portal venous branch during transjugular intrahepatic portosystemic shunt (TIPS) procedure may reduce the risk of postprocedural overt hepatic encephalopathy (HE). This study aimed to describe blood distribution under portography and combined it with puncture site to determine portal flow diversion, and to evaluate its prognostic value in predicting post-TIPS overt HE. METHODS: In this retrospective analysis of patients with cirrhosis undergoing TIPS, we included 252 patients to describe blood distribution under portography and 243 patients to assess the association between portal flow diversion and post-TIPS overt HE. RESULTS: At the first stage, 51 (20.2%) patients were identified as type A (unilateral type with the right portal branch receives blood from splenic vein [SV]), 16 (6.4%) as type B (unilateral type with the right branch receives blood from superior mesenteric vein [SMV]) and 185 (73.4%) as type C (fully mixed type). At the second stage, 40 patients were divided into the SV group, 25 into the SMV group and 178 into the mixed group. Compared with the mixed group, the risk of post-TIPS overt HE was significantly higher in the SMV group (adjusted HR 3.70 [95% CI 2.01-6.80]; p < 0.001), whereas the SV group showed a non-significantly decreased risk (adjusted HR 0.57 [95% CI 0.22-1.48]; p = 0.25). Additionally, the SMV group showed a substantial increase in ammonia level at 3 days and 1 month after procedure. CONCLUSIONS: Our results support the clinical use of portal flow diversion for risk stratification and decision-making in the management of post-TIPS overt HE.
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Encefalopatía Hepática , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Encefalopatía Hepática/complicaciones , Humanos , Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Derivación Portosistémica Intrahepática Transyugular/métodos , Portografía/métodos , Punciones/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To evaluate the changes of immune environment of distant tumors after combined microwave ablation (MWA) and anti- programmed death receptor - 1 (anti-PD-1) therapy, and assess the changes of systemic immune response. METHODS: Bilateral hepatocellular carcinoma model was established in mice, which were then subsequently treated with MWA, or anti-PD-1, or no treatment, or MWA + anti-PD-1. The contralateral tumor volume and mice survival time were recorded. Flow cytometry and immunohistochemistry were used for evaluation of the immune cells subgroup change of contralateral tumor. In addition, tumor rechallenge tests were conducted on unilateral tumor-bearing mice to examine the systemic immune effects of the combination therapy. RESULTS: We found that MWA treatment alone failed to produce a significant abscopal effect. In contrast, the combination group had longer survival than the MWA or anti-PD-1 group alone, with slower distant tumor growth. Moreover, the tumor-specific immune responses induced by combination therapy are stronger than anti-PD-1 or MWA alone. Combination therapy also elevated the levels of Th1-type cytokines in peripheral blood. In addition, after tumor rechallenge, the combination group showed more rejection to the reimplanted tumors (6 out of 10 mice). CONCLUSIONS: The combination of MWA and anti-PD-1 therapy resulted in the inhibition of distant tumor growth and the construction of a systemic anti-tumor immune environment that can reduce recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Modelos Animales de Enfermedad , Inmunoterapia , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Microondas/uso terapéuticoRESUMEN
PURPOSE: To investigate the clinical course and optimal management for spontaneous isolated intramural hematoma of the superior mesenteric artery (SIHSMA). METHODS: From January 2015 to October 2020, a total of 31 consecutive patients with SIHSMA were included in this study. The demographics, clinical features, treatment details, imaging information, and outcomes were reviewed. RESULTS: There were 24 males and 7 females, with a mean age of 54.9 years (SD 6.9 years). Seven patients (7/31, 23%) were associated with ulcer-like projection (ULP), one patient (1/31, 3%) with intramural blood pool (IBP), and the remaining twenty-three patients (23/31, 74%) had no ULP or IBP. All patients were initially managed conservatively and underwent a median follow-up of 25.5 months (IQR 14.5, 39.9), which showed 3 patients (3/31, 10%) subsequently underwent stenting (2 within 7 days and 1 after 1.5 months), 1 patient (1/31, 3%) progressed to a localized dissection 7 months later but remained stable and asymptomatic until the time of writing, and the remaining patients (27/31, 87%) had no progression. In the present cohort, the overall survival was 100% (31/31). The free-from progression and stenting rate under conservative treatment was 87% (27/31). The invasive intervention rate was 10% (3/31). The natural complete regression rate of IMH in patients without ULP was higher than those with ULP (91% [21/23] vs. 29% [2/7], p = .003). CONCLUSION: The majority of patients with SIHSMA can be managed conservatively. Patients with ULP seemed to have a lower IMH regression rate than those without ULP.
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Hematoma , Arteria Mesentérica Superior , Femenino , Hematoma/diagnóstico por imagen , Hematoma/cirugía , Humanos , Masculino , Arteria Mesentérica Superior/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del Tratamiento , Úlcera/complicacionesRESUMEN
The data on endovascular aortic repair (EVAR) for traumatic aortic dissection (TAD) are lacking. Hence, this study aimed to evaluate the efficacy of EVAR for TAD and report our experience based on patients from our medical center with a relatively long follow-up. A total of 25 consecutive patients with TAD underwent EVAR from October 2015 to October 2020. The demographics, imaging characteristics, clinical features, treatment details, and follow-up results were reviewed. Urgent EVAR was performed in 3 patients (12%), while the remaining 22 patients (88%) underwent delayed EVAR. Systematic heparinization was used in all patients during the endovascular procedure. The EVAR was technically successful in all patients, with no cases converted into open surgery. No death occurred during the perioperative period. One patient presented with a type II endoleak on postoperative 1-month CT images during a mean follow-up of 42.3 ± 17.7 months (5-67.5 months) and showed spontaneous regression of the endoleak without any intervention during the subsequent follow-up. All the patients survived until the time of writing, and none of them showed late endoleak, stent migration, paraplegia, and reintervention. The patients with left subclavian artery covered (n = 8) had no obvious ischemia of the arm and brain. The study results demonstrated that EVAR for TAD proved to be safe and effective, and most patients could undergo delayed EVAR. Systematically heparinization during EVAR under the setting of multi-trauma was safe.
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Aneurisma de la Aorta Abdominal , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Humanos , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Stents , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Patients indicated to transjugular intrahepatic portosystemic shunt (TIPS) placement may have splenectomy history due to thrombocytopenia. This study aimed to evaluate the effect of prior splenectomy on TIPS procedure and post-TIPS outcomes. METHODS: We conducted a longitudinal analysis based on a cohort of 284 patients with cirrhosis submitted to TIPS; 74 patients had splenectomy history (splenectomy group) and 210 did not (non-splenectomy group). Cox proportional hazards models were used to evaluate the association between splenectomy and outcomes after TIPS. The primary outcome was shunt dysfunction. Secondary outcomes included all-cause mortality, clinical recurrence of bleeding or ascites, and overt hepatic encephalopathy (OHE). RESULTS: During a median follow-up of 16.2 months, the splenectomy group had significantly lower rates of postoperative shunt patency (85.5% vs 95.6% at 1 year and 75.2% vs 86.5% at 2 years; adjusted hazard ratio [HR] 2.53; 95% confidence interval [CI] 1.21-5.12; P = 0.01) and higher risk of OHE (adjusted HR 1.82; 95% CI 1.03-3.54; P = 0.04). But the risk of mortality (adjusted HR 0.87; 95% CI 0.41-1.87; P = 0.73) and recurrent bleeding or ascites (adjusted HR 1.17; 95% CI 0.53-2.35; P = 0.77) showed no statistical difference. Multivariate analysis confirmed splenectomy history and endoscopic therapy as independent predictors of shunt dysfunction. Besides, pre-TIPS splenectomy increased the difficulty of TIPS procedure by complicating portal vein puncture. CONCLUSIONS: For patients with cirrhosis submitted to TIPS, prior splenectomy complicated TIPS procedure and increased the risk of shunt dysfunction and OHE after TIPS, but was not significantly associated with the occurrence of mortality and recurrent bleeding or ascites.
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Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Ascitis/etiología , Hemorragia Gastrointestinal/etiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Recurrencia Local de Neoplasia , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Estudios Retrospectivos , Esplenectomía/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The relationship between the improvement of sarcopenia and post-TIPS prognosis has not been fully investigated. AIMS: To assess what level of sarcopenia improvement is required for potential benefits to post-TIPS prognosis. METHODS: In this retrospective study, 109 cirrhotic patients with sarcopenia who underwent TIPS between February 2016 and January 2021 were included. The change in skeletal muscle index (SMI) at 6 months post-TIPS was assessed and the correlations of SMI improvement with clinical outcomes were analyzed. RESULTS: During follow up, 59 (65.6%) patients reversed from sarcopenic to non-sarcopenic, and the cumulative mortality (8.5 % vs. 26.0%, log rank P = 0.013) and incidence of overt hepatic encephalopathy (OHE) (18.6% vs. 44.0%, log rank P = 0.004) in patients who reversed were significantly lower than who did not. SMI improvement rate was identified as an independent risk factor for mortality and OHE. In addition, the cumulative survival rate of patients with sarcopenia reversal or SMI improvement rate > 10.4% was significantly higher than that of patients with an SMI improvement rate ≤ 10.4% (92.5% vs. 58.6%, log rank P < 0.001). CONCLUSION: Reversal of sarcopenia or significant SMI improvement by TIPS could reduce the risk of death and OHE.
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Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Sarcopenia , Humanos , Sarcopenia/etiología , Cirrosis Hepática/complicaciones , Estudios Retrospectivos , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Pronóstico , Encefalopatía Hepática/epidemiología , Resultado del TratamientoRESUMEN
Thrombocytopenia is the most frequent haematologic disorder in patients with cirrhosis, and it is perceived as a contributory factor for bleeding events. Cirrhosis patients with portal hypertension (PHT) is often accompanied with mild to moderate thrombocytopenia when they treated with transjugular intrahepatic portosystemic shunt (TIPS). To address whether the risk of variceal hemorrhage after TIPS varies with different platelet count in patients with normal platelet count and thrombocytopenia, we conducted the retrospective controlled study to evaluate the association of platelet count with the risk of variceal bleeding after TIPS. 304 patients were selected to the study. Propensity score matching was performed to adjust for potential selection bias. 63 patients from each group could be paired. Cox proportional hazards models were used to evaluate the association between platelet and variceal bleeding after TIPS. Platelet counts of two groups are 185.0 ± 98.7 × 109/L (normal platelet count) and 70.6 ± 39.3 × 109/L (thrombocytopenia) respectively. The bleeding rates of two groups in overall cohort are 10.9% (normal platelet count) and 12.9% (thrombocytopenia). After matched, the bleeding rates of two groups are 11.1% (normal platelet count) and 14.3% (thrombocytopenia) There was no statistically significant difference in bleeding rates between the two groups, either in the whole cohort (P = 0.671) or in the matched cohort (P = 0.593). Platelet count was not associated with bleeding events after TIPS (hazard ratio (HR) 95% confidence interval: 0.986-1.005, P = 0.397 in normal platelet count and 95% confidence interval: 0.968-1.020, P = 0.648 in thrombocytopenia). Thrombocytopenia in patients with cirrhosis was not associated with the risk of variceal bleeding episodes post-TIPS. Thrombocytopenia should not be viewed as an absolute contraindication for TIPS.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Trombocitopenia , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Estudios Retrospectivos , Hemorragia Gastrointestinal/cirugía , Hemorragia Gastrointestinal/complicaciones , Trombocitopenia/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Resultado del TratamientoRESUMEN
Background and aims: Nonalcoholic steatohepatitis (NASH) has become one of the major causes of cirrhosis and liver failure. However, there are currently no approved medications for managing NASH. Our study was designed to assess the effects of ginkgetin on NASH and the involved mechanisms. Methods: We constructed a mouse model of NASH by high-fat diet for 24 weeks. The effects of ginkgetin on NASH were evaluated by histological study, Western blot, and biochemical analysis. RNA Sequencing (RNA-Seq) analysis was used to investigate the alteration in gene expression and signaling pathways at bulk and single-cell levels. Results: Administration of ginkgetin resulted in a marked improvement in hepatic lipid accumulation, inflammation, and fibrosis in the NASH model. And these results were supported by bulk RNA-Seq analysis, in which the related signaling pathways and gene expression were markedly downregulated. Furthermore, single-cell RNA-Seq (scRNA-Seq) analysis revealed that the effects of ginkgetin on NASH were associated with the reprogramming of macrophages, hepatic stellate cells, and endothelial cells. Especially, ginkgetin induced a marked decrease in macrophages and a shift from pro-inflammatory to anti-inflammatory phenotype in NASH mice. And the NASH-associated macrophages (NAMs), which emerge during NASH, were also significantly downregulated by ginkgetin. Conclusion: Ginkgetin exhibits beneficial effects on improving NASH, supported by bulk and single-cell RNA-Seq. Our study may promote pharmacological therapy for NASH and raise the existent understanding of NASH.
RESUMEN
Background: Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Methods: Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. Results: The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Conclusions: Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.