Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. RESULTS: Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. CONCLUSIONS: The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.

Kidney invasion occurred 2 years following liver transplantation for hepatic alveolar echinococcosis: a case report.

BACKGROUND: The organ most commonly invaded in echinococcosis is the liver; the lungs, brain, kidneys, heart, and spleen are rarely invaded, and multi-organ involvement in echinococcosis is even rarer. No studies have reported renal invasion after liver transplantation for hepatic alveolar echinococcosis. CASE PRESENTATION: We report here a case of renal invasion 2 years after allogeneic liver transplantation in a 53-year-old female patient with hepatic alveolar echinococcosis combined with lung metastases. At the time of the first consultation, the lesion had been found to involve the second hepatic hilum combined with lung metastases, but the patient requested conservative treatment, and the lesion was not controlled by taking albendazole for 3 years. After discussion in the treatment group, it was decided to use allogeneic liver transplantation and lung segmental resection for surgical treatment, after which the patient was put on long-term oral immunosuppression. She was hospitalized 2 years later for low back pain and diagnosed with renal alveolar echinococcosis. Due to significant compression and left-sided renal insufficiency, the final option was to remove the diseased kidney. It is worth mentioning that signs of unexplained urinary tract infection were present throughout the course of treatment. CONCLUSION: This study suggests that extra attention should be paid to the presence of cryptogenic lesions in patients with hepatic alveolar echinococcosis who already have definite metastatic lesions. Immunosuppressive drugs after liver transplantation in patients with hepatic echinococcosis may cause occult lesions to develop into active ones. In clinical practice, particular attention should be paid to patients with hepatic alveolar echinococcosis with long-term concomitant signs of unexplained urinary tract infections, which may be a precursor clinical feature of cryptogenic renal alveolar echinococcosis.

Transarterial Chemoembolization Plus Sorafenib versus Transarterial Chemoembolization Alone for Advanced Hepatocellular Carcinoma: An Umbrella Review of Meta-Analyses and Systematic Reviews.

Background: Sorafenib is the standard treatment for most cases of advanced hepatocellular carcinoma (HCC), based on Western and Eastern clinical guidelines. Thus, an increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapies have been used in clinical practice. In addition, several systematic reviews and meta-analyses have explored the efficacy and safety of the combination of TACE and sorafenib. Therefore, we performed an umbrella review to summarize and evaluate these evidence-based studies. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to June 1, 2023. All meta-analyses that evaluated the effect of TACE plus sorafenib on HCC were considered eligible. The quality of the included meta-analyses was evaluated by AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). The quality of evidence per association provided in the meta-analyses was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). This study was registered with PROSPERO (Registration ID: CRD42023420417). Results: We included 12 meta-analyses, including randomized clinical trials, cohort studies, and observational studies. A total of 44 associations with overall survival, survival rate, time to disease progression, overall response rate, disease control rate, and adverse events were evaluated in this umbrella review. The quality of most associations ranged from low to very low, indicating that flaws were significant in the current meta-analyses. Conclusion: This umbrella review identified beneficial associations between TACE and sorafenib combination therapy in advanced HCC. However, owing to the low certainty of the evidence, clinicians should interpret our results with caution when applying them in clinical practice, and high-quality studies are required in the future to confirm our results.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: We carried out a systematic review and meta-analysis to assess the safety and effectiveness of hepatic arterial infusion chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Eligible studies were searched by MEDLINE, the Cochrane Library, Embase, and Web of Science from January 1995 to January 2022, investigating eligible literature comparing HAIC and TACE for patients with HCC. The main outcome measures included progression-free survival (PFS), overall survival (OS), adverse events (AEs), objective response rate (ORR), and diseases control rate (DCR). RESULTS: Eight literature and 1028 patients were enrolled in this meta-analysis. The pooled PFS, OS, ORR, and DCR were HR = 0.89 (95% CI, 0.81-0.98), HR = 0.84 (95% CI, 0.75-0.93), OR = 2.77 (95% CI, 2.01-3.80), and OR = 4.64 (95% CI, 2.40-8.99), respectively. The adverse events of HAIC were lower than TACE. CONCLUSION: Our meta-analysis revealed that HAIC can achieve a better effect and survival benefits than TACE in patients with uHCC.

Construction and validation of a prediction model of extrahepatic metastasis for hepatocellular carcinoma based on common clinically available data.

Objective: This study aimed to investigate the clinical characteristics and risk factors of patients with hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM) and to establish an effective predictive nomogram. Methods: Clinical and pathological data from 607 patients with hepatocellular carcinoma admitted to the Affiliated Hospital of Qinghai University between 1 January 2015 and 31 May 2018 were documented, as well as demographics, clinical pathological characteristics, and tumor-related parameters to clarify clinical risk factors for HCC EHM. These risks were selected to build an R-based clinical prediction model. The predictive accuracy and discriminating ability of the model were determined by the concordance index (C-index) and the calibration curve. The results were validated with a bootstrap resample and 151 patients from 1 June 2018 to 31 December 2019 at the same facility. Results: In multivariate analysis, independent factors for EHM were neutrophils, prothrombin time, tumor number, and size, all of which were selected in the model. The C-index in the EHM prediction model was 0.672 and in the validation cohort was 0.694. In the training cohort and the validation cohort, the calibration curve for the probability of EHM showed good agreement between the nomogram prediction and the actual observation. Conclusion: The extrahepatic metastasis prediction model of hepatocellular carcinoma constructed in this study has some evaluation capability.

Ruptured Hepatocellular Carcinoma: What Do Interventional Radiologists Need to Know?

Rupture of HCC (rHCC) is a life-threatening complication of hepatocellular carcinoma (HCC), and rHCC may lead to a high rate of peritoneal dissemination and affect survival negatively. Treatment for rHCC mainly includes emergency surgery, interventional therapies, and palliative treatment. However, the management of rHCC should be carefully evaluated. For patients with severe bleeding, who are not tolerant to open surgery, quick hemostatic methods such as rupture tissue ablation and TAE/TACE can be performed. We described clinical presentation, prognosis, complication, interventional management, and current evidence of rHCC from the perspective of interventional radiologists. Overall, our review summarized that interventional therapies are necessary for most patients with rHCC to achieve hemostasis, even in some patients with Child-Pugh C. Moreover, TAE/TACE followed by staged hepatectomy is a beneficial treatment for rHCC according to current clinical evidence. TAE/TACE is the first choice for most patients with rHCC, and appropriate interventional treatment may provide staged surgery opportunities for those who are not tolerant to emergency surgery to reach an ideal prognosis.

Greater than or equal to 8 mm is a safe diameter of common bile duct for primary duct closure: single-arm meta-analysis and systematic review.

Greater than or equal to 8 mm was often used as the safe diameter of primary duct closure (PDC) after laparoscopic common bile duct exploration (LCBDE) in previous studies, but it is impossible to verify the source of this safe diameter, and lack of evidence for the safe diameter of PDC. Hence, this study evaluates the incidence of postoperative complications by single-arm meta-analysis to demonstrate the feasibility of using 8 mm as the safe diameter of PDC, so as to provide reference for clinical selection. Eligible studies were searched by MEDLINE, the Cochrane Library, Embase, and Web of Science from January 1995 to May 2021, investigating eligible literature using PDC after LCBDE for methods of common bile duct closure. The single-arm meta-analysis was analyzed by "meta" package under R 4.0.5, and the pooled incidence of postoperative complications was calculated. Twelve literatures were enrolled in this single-arm meta-analysis including 792 patients. The pooled complications rate including total complications (13.1%, 95% CI 10.1-15.6%), total biliary duct-related complications (9.4%, 95% CI 7.4-11.6%), residual stones (1.3%, 95% CI 0.3-2.7%), bile leakage (5.1%, 95% CI 3.5-6.9%), postoperative pneumonia (2.1%, 95% CI 0.8-3.8%), postoperative acute pancreatitis (1.8%, 95% CI 0.2-4.3%), and stone recurrence (2.6%, 95% CI 1.1-4.4%). The clinical indication of PDC after LCBDE should follow that the diameter of common bile duct ≥ 8 mm as the safe diameter.

Transjugular Intrahepatic Portosystemic Shunt for Portal Vein Cavernous Transformation: A Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is technically challenging in the treatment of portal vein cavernous transformation (PVCT), and there is no high-quality evidence regarding whether it is an option for patients with PVCT. We carried out a systematic review and meta-analysis to assess the feasibility and safety of TIPS for PVCT. METHODS: Systematic search of PubMed, Chinese National Knowledge Infrastructure (CNKI) database, Cochrane Library, Embase, and Wanfang database through December 2021 for appropriate studies reporting efficacy and safety in patients with PVCT undergoing TIPS. The main outcome included the technical success rate, postoperative rebleeding rate, postoperative hepatic encephalopathy rate, stent patency rate, preoperative, and postoperative portal pressure. RESULTS: Ten studies, including 292 patients were included. Our results showed that TIPS was technically successful in 82.97% (95% confidence interval [CI]: 77.14%-88.41%, p = 0.297) with low heterogeneity (I2 = 18.39%, p = 0.279). Postoperative rebleeding occurred in 9.56% (95% CI: 4.55%-16.77%, p = 0.073) with moderate heterogeneity (I2 = 46.45%, p = 0.06). Postoperative hepatic encephalopathy occurred in 18.55% (95% CI: 9.23%-27.05%, p = 0.343) with moderate heterogeneity (I2 = 48.62%, p = 0.049). Stent patency during follow-up was in 78.43% (95% CI: 70.74%-85.20%, p = 0.805) with low heterogeneity (I2 = 0%, p = 0.654). Postoperative portal pressure significantly reduced (WMD = 12.79 mm Hg, 95% CI: 12.09-13.48 mm Hg, p < 0.00001) with high heterogeneity (I2 = 61.4%, p = 0.02). Both Begg test and funnel plot showed that there was no significant publication bias. CONCLUSIONS: TIPS is feasible and safe in patients with PVCT and PVCT should not be considered an absolute contraindication to TIPS.

Low vs standardized dose anticoagulation regimens for extracorporeal membrane oxygenation: A meta-analysis.

BACKGROUND: To compare the safety and efficacy of low-dose anticoagulation (LA) with that of standardized dose anticoagulation (SA) for patients supported with extracorporeal membrane oxygenation (ECMO). METHODS: PubMed, MEDLINE, the Cochrane Library, and Web of Science were screened for original articles. Screening was performed using predefined search terms to identify cohort studies reporting the comparison of LA with SA in patients supported with ECMO from Nov 1990 to Jun 2020. The effect size was determined by the odds ratio (OR) with the 95% confidence interval (CI). RESULTS: An analysis of 7 studies including a total of 553 patients was performed. LA (Low-heparin group) was administered to 255 patients, whereas the other 298 patients received SA (Full-heparin group). The incidence of gastrointestinal tract hemorrhage (OR 0.36, 95% CI 0.20-0.64) and surgical site hemorrhage (OR 0.43, 95% CI 0.20-0.94) were significantly lower in patients who underwent LA compared with that in those who underwent SA. The rates of hospital mortality (OR 0.81, 95% CI 0.42-1.56), successfully weaning off of ECMO (OR 0.80, 95% CI 0.30-2.14), pulmonary embolism (OR 0.79, 95% CI 0.24-2.65), intracardiac thrombus (OR 0.34, 95% CI 0.09-1.30), intracranial hemorrhage (OR 0.62, 95% CI 0.22-1.74), and pulmonary hemorrhage (OR 0.77, 95% CI 0.30-1.93) were similar between the two groups. CONCLUSIONS: This meta-analysis confirms that LA is a feasible and safe anticoagulation strategy in patients supported by ECMO. Future studies should focus on the long-term benefits of LA compared with SA.

[Removal of Oxytetracycline from Water Using Blast Furnace Slag Loaded Sulfide Nanoscale Zero-valent Iron].

Blast furnace slag loaded with sulfide nano zero valent iron (S-nZVI@BFS) was applied to remove oxytetracycline (OTC) from water. S-nZVI@BFS was synthesized via liquid reduction and characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer, Emmett and Teller (BET) theory. The effect of reaction time, initial concentration of OTC, initial pH, and coexisting hexavalent chromium[Cr(Ⅵ)] were investigated. The results show that Fe and S were successfully immobilized on the surface of S-nZVI@BFS, the specific surface area and pore volume of which increased to 141.986 m2·g-1 and 0.388 cm3·g-1, respectively, following the loading of nZVI and sulfurization. The utilization rate of the surface active sites of S-nZVI@BFS was improved with an increase of the initial concentration of OTC; the removal rate increased from 20.12 mg·g-1 to 202.74 mg·g-1 when the initial concentration of OTC was increased from 10 mg·L-1 to 100 mg·L-1. The removal rate decreased with pH, declining from 99.78 mg·g-1 to 41.12 mg·g-1 when pH was increased from 3 to 11 due to the switch from Fendon oxidation to electrostatic adsorption. There was notable competition between OTC and Cr(Ⅵ) meaning that Cr(Ⅵ) can inhibit the removal of OTC, which is dose dependent.

Reduction and immobilization of Cr(VI) in aqueous solutions by blast furnace slag supported sulfidized nanoscale zerovalent iron.

In this study, an industrial waste-blast furnace slag (BFS) supported sulfidized nanoscale zerovalent iron (S-nZVI@BFS) was prepared and used for synergistic reduction and adsorptive removal of Cr(VI) from aqueous solutions. The characterization analysis showed that Fe0 and FeS were well dispersed on the surface of BFS, and the specific surface area of S-nZVI@BFS was 141.986 m2 g-1. Batch experiments demonstrated that the removal capacity of Cr(VI) was as high as 184 mg/g for S-nZVI@BFS. The pseudo-second-order kinetic model fitted the Cr(VI) removal kinetics well. Cr(VI) removal on the S-nZVI@BFS relied highly on pH values. The reduced Cr(VI) precipitated on S-nZVI@BFS mainly as CrxFe(1-x)(OH)3, CrxFe(1-x) OOH and Cr2S3, and the alkaline capacity of the BFS could efficiently prevent the release of Cr(III) from the precipitations in acid condition. Thus, supporting S-nZVI on BFS was an effective and safe method for Cr(VI) removal from aqueous solutions.

Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

BACKGROUND AND AIMS: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT. METHODS: Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non-AT groups based on whether AT was administered or not. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems. RESULTS: A total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non-AT group (43.0 months vs 21.0 months, P = .015; 16.0 months vs 11.0 months, P = .045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P = .023; P = .046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only "middle-risk" patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P = .033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P = .039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P = .007). CONCLUSION: With the current data, we conclude that AT benefits ICC patients following radical resection, especially those "middle-risk" patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation.

The effect of adjuvant therapy for patients with intrahepatic cholangiocarcinoma after surgical resection: A systematic review and meta-analysis.

BACKGROUD: Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection. PATIENTS AND METHODS: PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: 22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76). CONCLUSION: With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed.

Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma after radical hepatectomy: a real world study.

Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5 cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p = .43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p = .038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50 years, no cirrhosis, AFP ≤ 200 ng/ml, surgical margin <1 cm, tumor diameter >5 cm, no capsule, no satellite, or CN stage Ib/IIa (all p < .05), but patients with age < 50 years, tumor size ≤5 cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p < .05).Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50 years, tumor size >5 cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.