Introduction

Iodinated contrast (IC) is one of the leading causes of acute kidney injury (AKI). Nephrotoxicity of IC in cirrhosis is a debated issue due to low-quality evidence.

Aims & Methods

This study aims to evaluate the association between exposition to IC in cirrhotic patients and the development of AKI. We performed a systematic review in PubMed, Embase and Cochrane databases, searching for studies conducted in cirrhotic patients exposed to IC. The primary outcomes were: 1) AKI development in cirrhotic patients exposed or not to IC; and 2) AKI development in cirrhotic and health patients exposed to IC. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

The meta-analyses included 4 studies and 1,055 patients. Three studies (911 patients) evaluated cirrhotic patients exposed or not exposed to IC. There was a significant increase in AKI in cirrhotic patients exposed to IC (OR 3.10; 95% CI 1.45 to 6.61, p=0.003; I2=0%). Three studies (654 patients) evaluated cirrhotic and health patients exposed to IC. There was no difference in AKI comparing both groups (OR 1.61; 95% CI 0.63 to 4.16, p=0.322; I2=0%).

Conclusion

Patients with cirrhosis exposed to IC showed higher incidence of AKI compared with those not exposed, but when compared with health individuals also exposed to IC the incidence of AKI seems to be the same.

References

1. Campion D, Rizzo M, Ponzo P, Risso A, Giovo I, Rizzi F, et al. Risk of contrast-induced acute kidney injury in cirrhotic patients undergoing computed tomography: myth or reality? J Hepatol. 2020;73:S702.
2. Campion D, Ponzo P, Risso A, Caropreso P, Caviglia GP, Sanavia T, et al. A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis. J Hepatol. 2024;80(1):62–72.
3. Filomia R, Maimone S, Caccamo G, Saitta C, Visconti L, Alibrandi A, et al. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography. Medicine (Baltimore). 2016 Sep;95(38):e4836.
4. Safi W, Rauscher I, Umgelter A. Contrast-induced acute kidney injury in cirrhotic patients. A retrospective analysis. Ann Hepatol. 2015 Nov;14(6):895–901.
5. Visconti L, Filomia R, Maimone S, Montuori F, Ricciardi CA, Di Mauro E, et al. SP211ACUTE KIDNEY INJURY IN CIRRHOTIC PATIENTS UNDERGOING CONTRAST-ENHANCED COMPUTED TOMOGRAPHY. Nephrol Dial Transplant. 2015 May;30(suppl_3):iii448–iii448.

Introduction

Renal impairment is a common complication in cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in diagnosis of the different types of acute kidney injury (AKI) in cirrhosis.

Aims & Methods

This study aims to evaluate the accuracy of NGAL in the differential diagnosis of acute tubular necrosis (ATN) in cirrhosis. We performed a systematic review in PubMed, Embase and Cochrane databases, searching for studies analyzing NGAL as a biomarker of ATN. Statistical analysis included data pooling and heterogeneity testing. Quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

Results

The meta-analyses included 3 studies and 317 patients. The NGAL cut-off evaluated were similar between the three studies (delta 143 to 244μg/g). The pooled sensitivity and specificity of NGAL in predicting ATN in cirrhosis were 78.7% (95% CI 68.4% to 86.4%) and 80.8% (95% CI 55.5% to 93.4%). The AUC was 0.866 (95% CI 0.646 to 0.955).

Conclusion

In patients with cirrhosis, urinary NGAL is a good predictor of ATN and can be used as an additional tool to the differential diagnosis of acute kidney injury.

Introduction

Bacterial translocation exacerbates circulatory dysfunction present in patients with liver cirrhosis. Probiotics can reduce bacterial translocation and consequently improve the outcomes in this population.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in the cirrhotic patients. We performed a systematic review in PubMed, Embase and Cochrane Central database, searching for studies analyzing the effects of probiotics use in overt hepatic encephalopathy incidence in cirrhotic patients. A Bayesian network meta-analysis was conducted to estimate the relative effects between treatments using risk ratios (RR) and to rank each one according to the Surface Under the Cumulative Ranking Curve (SUCRA).

Results

We included eight studies, comprising 975 patients. The assessment of SUCRA values indicated that lactulose plus probiotics (0.95) emerged as the most effective prevention for overt hepatic encephalopathy. Moreover, lactulose plus probiotics demonstrated superior efficacy compared to lactulose (0.54), probiotics only (0.51), LOLA (0.48), placebo (0.24), and no therapy (0.21). The risk of overt hepatic encephalopathy was low for lactulose plus probiotics (0.000025; credible interval [CrI] 1.3x1016, 1.5), lactulose only (RR 0.64; CrI 0.09, 4.0), probiotics (RR 0.69; CrI 0.17, 2.9), LOLA (RR 0.64; CrI 0.04, 8.9) and no therapy (RR 1.1; CrI 0.22, 7.0).

Conclusion

In our network meta-analysis, the best results in the treatment of the patients with cirrhosis and hepatic encephalopathy was seen with the association of lactulose plus probiotics. Both drugs have good tolerability and are widely disponible, so we suggest considering this association.

Introduction

Standard treatment of autoimmune hepatitis (AIH) typically includes a combination of azathioprine and corticosteroids. However, approximately 20% of patients do not respond well to this conventional therapy. In this scenario, mycophenolate mofetil (MMF) may be used as an alternative treatment for patients with intolerance or non-response to first-line options.

Aims & Methods

This study aims to evaluate the performance of MMF in intolerant or non-responders patients with AIH previously treated with conventional therapy. We performed a systematic review in PubMed, Embase, and Cochrane databases. We analyzed overall remission, remission at AZA intolerance, and remission at AZA non-response. We also compared the outcome of overall remission in patients with AZA intolerance vs. AZA non-response. Statistical analyses were performed using R language 4.3.1.

Results

21 studies and 646 patients were included. The pooled overall remission rate was 62.21 (95% CI 54.31, 70.10). We found an overall remission rate of 66.74 (95% CI 57.48, 76.00) in patients intolerant to AZA, and 27.80 (95% CI 11.56, 44.04) in AZA non-responders. The comparison of overall remission in both groups favored the intolerance group (OR 4.98; 95% CI 1.69, 14.72; p = 0.004).

Conclusion

MMF is effective in inducing remission in patients with AIH who failed the first-line treatment. The overall effect is more prominent in patients who failed conventional therapy due to intolerance. Non-response to AZA may be correlated to suboptimal response to MMF as well.

Introduction

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths. Unresectable HCC can be treated with transarterial chemoembolization (TACE), which causes hypoxia and induces the expression of vascular endothelial growth factor (VEGF). Antiangiogenic drugs can be useful in this setting.

Aims & Methods

This study aims to compare TACE plus Apatinib (antiangiogenic drug, TACE+A) versus TACE plus Apatinib plus Camrelizumab (immune checkpoint inhibitor, TACE+AC). We performed a systematic review in PubMed, Embase, Cochrane and Web of Science databases, searching for studies comparing TACE+A versus TACE+AC in patients with unresectable HCC. The primary outcomes were overall survival and disease-free progression survival. The secondary outcomes were treatment response and adverse events grade III or IV. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics. ​

Results

The meta-analyses included 3 studies and 1,134 patients. There was a significant difference favoring TACE+AC in overall survival (HR 0.41; 95% CI 0.28 to 0.60; p<0.01; I²=87%) and in disease-free progression survival (HR 0.29; 95% CI 0.15 to 0.55; p<0.01; I0²=0%) compared to TACE+A. There is no difference in adverse events grade III or IV between groups (OR 1.08; 95% CI 0.83 to 1.40; p=0.586; I²=0%).

Conclusion

In patients with unresectable HCC, TACE+AC demonstrated superior efficacy compared to TACE+A. The two combinations showed similar safety profiles.

References

1. Duan X, Li H, Kuang D, Chen P, Zhang K, Li Y, et al. Transcatheter arterial chemoembolization plus apatinib with or without camrelizumab for unresectable hepatocellular carcinoma: a multicenter retrospective cohort study. Hepatol Int. 2023 Aug;17(4):915–26.
2. Liu H, Yu Q, Gu T, Qu P, Ma X, Zhou S, et al. Transarterial Chemoembolization plus Apatinib with or without Camrelizumab for the Treatment of Advanced HBV-related Hepatocellular Carcinoma. J Gastrointest Liver Dis JGLD. 2023 Jun 22;32(2):182–9.
3. Zhu D, Ma K, Yang W, Zhou HF, Shi Q, Ren JW, et al. Transarterial chemoembolization plus apatinib with or without camrelizumab for unresected hepatocellular carcinoma: A two-center propensity score matching study. Front Oncol. 2022;12:1057560.

Introduction

There are two types of covered self-expandable metallic stents (CSEMS): laser-cut (L) and braided (B). The B-type has a strong axial force and can cause problems such as recurrent obstructive jaundice and cholangitis. The L-type is less stressful for the bile duct.

Aims & Methods

This study aims to compare CSEMS B-type versus L-type in patients with unresectable distal malignant biliary obstruction. We performed a systematic review in PubMed, Embase and Cochrane databases, searching for studies comparing both types of CSEMS in this population. The primary outcome was stent occlusion. The secondary outcomes were tumor ingrowth, tumor overgrowth, stent migration, pancreatitis and cholecystitis. The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics.

Results

The meta-analyses included 4 studies and 430 patients. There was no significant difference for any outcome: stent occlusion (OR 1.28; 95% CI 0.73 to 2.23; p=0.388; I²=0%), tumor ingrowth (OR 1.12; 95% CI 0.46 to 2.76; p=0.800; I²=0%), tumor overgrowth (OR 1.23; 95% CI 0.36 to 4.25; p=0.740; I²=0%), stent migration (OR 1.60; 95% CI 0.28 to 9.20; p=0.600; I²=73%), pancreatitis (OR 1.28; 95% CI 0.53 to 2.90; p=0.559; I²=0%) and cholecystitis (OR 0.73; 95% CI 0.26 to 2.06; p=0.553; I²=0%).

Conclusion

In patients with distal malignant biliary obstruction, no significant difference was observed between CSEMS B-type and L-type.

References

1. HASEGAWA, S. et al. Braided-type stent versus laser-cut-type stent for patients with unresectable distal malignant biliary obstruction: a randomized controlled trial. Gastrointestinal Endoscopy, v. 99, n. 5, p. 739-746.e1, 1 maio 2024.
2. OKUNO, M. et al. The evaluation of bilateral stenting using braided or laser-cut self-expandable metallic stent for malignant hilar biliary obstruction. Surgical Endoscopy, v. 37, n. 11, p. 8489–8497, 1 nov. 2023.
‌3. KITAGAWA, K. et al. Laser-cut-type versus braided-type covered self-expandable metallic stents for distal biliary obstruction caused by pancreatic carcinoma: a retrospective comparative cohort study. Clinical Endoscopy, v. 55, n. 3, p. 434–442, 1 maio 2022.
​4. TANISAKA, Y. et al. Can the laser-cut covered self-expandable metallic stent be the first choice for patients with unresectable distal malignant biliary obstruction? (with video). Journal of Hepato-Biliary-Pancreatic Sciences, v. 29, n. 5, p. 585–593, 1 maio 2022.
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Introduction

Mycophenolate mofetil (MMF) is considered an alternative treatment for patients with autoimmune hepatitis (AIH) who have insufficient response to azathioprine (AZA). However, it is hypothesized that MMF may be more effective than AZA to induce remission in treatment-naive patients as well.

Aims & Methods

This study aims to compare the effectiveness of MMF and AZA in inducing remission in patients with treatment-naive AIH. PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials and observational studies. The primary outcome was complete biochemical remission (CBR) at the end of the follow-up period. The secondary outcome was non-response rate. Heterogeneity was examined using I² statistics, and a random-effects model was employed. Review manager 5.4 was used for statistical analyses.

Results

The meta-analysis included 3 studies (1 RCT and 2 observational) and 265 patients (180 in the MMF group vs. 85 in the AZA group). CBR was significantly higher in the MMF group (OR 3.81; 95% CI 1.98 to 7.36; p < 0.0001; I2 = 0%). There was no significant difference between groups regarding the non-response rate (OR 0.46; 95% CI 0.14 to 1.52; p = 0.20; I2 = 53%).

Conclusion

In patients with treatment-naive AIH, MMF is more effective in inducing CBR compared to conventional treatment with AZA. Larger RCTs are needed to consolidate the evidence of MMF's impact on AIH treatment as a first-line agent and to provide concise insights for guiding clinical decisions.