Outcome of liver transplantation in hepatic glycogen storage disease: A systematic review and meta-analysis.

INTRODUCTION: Liver transplantation (LT) is the choice of therapeutic option for end-stage hepatic GSD patients; however, reports about the long-term outcome of LT in these patients have remained controversial. METHODS: We performed a systematic review and meta-analysis of observational studies published until Dec 31, 2021, that investigated the long-term outcome of LT in hepatic GSD patients. A literature search in the MEDLINE/PubMed, EMBASE,Cochrane Library, Scopus and Web of Science Core Collection databases was performed. RESULTS: 14 studies with 210 patients were included in our analysis. As the results showed, the pooled proportion of GSD patients with complications after liver transplant (e.g., hemorrhagic shock, biliary complications, tacrolimus encephalopathy, chronic hepatitis, hepatic artery thrombosis, hepatic adenoma, sepsis, liver dysfunction, chronic rejection, acute cellular rejection, and CMV infection) was 27.7% (95% CI: 20.42-35.67) without heterogeneity (I2  = 24.04%), as calculated by the random-effect model. The pooled proportion of GSD patients with complications related to GSD after LT, including HCC (Hepatocellular carcinoma), renal complication, muscle problems, delayed menarche, persistent neutropenia, pneumonitis, renal failure, and hepatic adenoma was 22.2% (95% CI: 7.97-40.01) with high heterogeneity (I2  = 82.47%). Subgroup analysis including the age of patients (adult/pediatric), duration of follow-up, and type of donor was conducted to investigate the resources of heterogeneity. CONCLUSION: According to our investigation and review analysis, most GSD patients showed significant outcome improvement after liver transplantation. Overall, our findings showed an excellent outcome of liver transplantation in GSD patients; however, it needs further investigations to be confirmed.

The mutation spectrum and ethnic distribution of non-hepatorenal tyrosinemia (types II, III).

BACKGROUND: Different types of non-hepatorenal tyrosinemia are among the rare forms of tyrosinemia. Tyrosinemia type II and III are autosomal recessive disorders caused by pathogenic variants in the tyrosine aminotransferase (TAT), and 4-hydroxyphenyl-pyruvate dioxygenas (HPPD) genes, respectively. There are still unclarified aspects in their clinical presentations, mutational spectrum, and genotype-phenotype correlation. MAIN BODY: In this study, we evaluated the spectrum of TAT and HHPD gene mutations in patients with tyrosinemia type II and III. Moreover, biochemical and clinical findings are evaluated to establish a genotype-phenotype relationship in the above-mentioned patients. Thirty-three TAT variants have been reported in 42 families, consisting of 21 missense variants, 5 frameshift variants, 4 nonsense variants, 2 variants that primarily cause splicing site, and 1 skipping complete exon (large deletion). The most common variant is p.Arg57Ter, causing a splicing defect, and resulting in premature termination of translation, which was found in 10 patients from 3 families. In HPPD gene, eleven variants in 16 patients have been reported including 7 missense variants, 2 nonsense variants, 1 splice defect, and 1 frameshift variant so far. All variants are unique, except for p.Tyr160Cys, which is a missense variant found in two different patients. Regarding genotype-phenotype correlations, in 90% of tyrosinemia type II patients, positive clinical and biochemical correlations with a detected variant are observed. In HPPD gene, due to the small number of patients, it is not possible to make a definite conclusion. CONCLUSION: This is the first large review of variants in TAT and HPPD, highlighting the wide spectrum of disease-causing mutations. Such information is beneficial for the establishment of a privileged mutation screening process in a specific region or ethnic group.

Effectiveness of islet transplantation in diabetes mellitus type 1: a systematic review of the recent evidences.

INTRODUCTION: Islet transplantation has been introduced as a promising approach for the treatment of diabetes mellitus type 1. Despite many efforts to achieve a perfect treatment, further investigation is still needed to eliminate limitations and challenging issues. The objective of the present systematic review is to evaluate the efficacy of islet transplantation in diabetes mellitus type 1. EVIDENCE ACQUISITION: We conducted a systematic review on the results of clinical studies on islet cell transplantation between January 2015 and November 2021. The Search strategy was designed and conducted in PubMed, Cochrane, Scopus, and Web of Science. EVIDENCE SYNTHESIS: Studies have indicated that islet transplantation can reduce the daily insulin requirement as well as improving metabolic stability in diabetic patients. Even in some patients, insulin independence was achieved during the first year of transplantation. CONCLUSIONS: Findings show that islet transplantation has a potential to become a promising treatment for diabetes mellitus type 1. In this regard, to obtain a trustworthy result, it is essential to design clinical studies (RCTs) with large sample size and long follow-up (cohort studies) to achieve a comprehensive and accurate appraisal of islet transplantation.

Ethical consumption: why should we understand it as a social practice within a multilevel framework?

This article discusses the importance of a multilevel and intertwined understanding of ethical consumption given its conjunction with other social practices. Although the literature on ethical consumption is vast, the role of sociotechnical regimes including technological and cultural elements, infrastructure, market and regulation has been mainly overlooked in this literature. This may be so because ethical consumption practices that refer to other-oriented consumption practices are mainly considered in the view of the motivations and preferences of individual consumers. Due to the insufficiency of individualistic approaches in explaining stimulators and inhibitors of ethical consumption, there might be "various constraints" and "competing demands" in society which limit the formation of "ethical consumption". Therefore, to avoid an oversimplified view of ethical consumption, this paper contributes with a theoretical discussion on combining social practice theory (SPT) with a multi-level perspective (MLP). Although the SPT is a very well-structured framework in consumption studies, the necessity of a combined approach concerns the often-insufficient attention paid to structural prerequisites of various consumption forms in social practice theories. By understanding ethical consumption practices according to a multi-level framework, the paper emphasizes the importance of structural factors at macro- and mesolevels. It also contributes attention to how ethical consumption grows due to dialectical processes between levels, showing that niche practices can simultaneously challenge and rely on existing regimes.

Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature.

BACKGROUND: Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue diagnosis, either histopathology or enzyme assay, are invasive. Meanwhile, GSDs are diseases with significant genetic heterogeneity, and gene-sequencing methods can be more useful. This systematic review aims to review the literature to assess the value of massively parallel sequencing in the diagnosis of GSDs on patients with previously undiagnosed hepatic involvement. METHODS: Relevant studies identified in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science Core Collection databases up to July 2019 with no time and language restrictions. Publications were included in the review if they analyzed GSDs with hepatic involvement (GSD I, GSD III, GSD IV, GSD VI, GSD IX), using targeted gene sequencing (TGS) or exome sequencing (ES). RESULTS: Eleven studies were included in this systematic review. ES demonstrated a 93% diagnostic yield. These methods correctly distinguished all types of pathogenic variants. The diagnostic yield of the TGS method was around 79.7%. CONCLUSIONS: According to our results, TGS analysis can be considered as the first-line diagnostic method with valuable results and ES can be used to diagnose complex cases of GSD with liver involvement. Overall, these molecular methods are considered as accurate diagnostic tools, which expedite correct diagnosis and treatment with significant cost-effectiveness by reducing unnecessary and inaccurate tests. PROSPERO REGISTRATION: CRD42020139931. Registered 8 January 2020.

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis.

Background: The impact of de novo anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of de novo DSAs on the outcome in LT. Methods: We did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported de novo DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed. Results: Of 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with de novo DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94-6.71, P < 0.001; I2 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17-13.04; P < 0.001; I2 49.77%); they were compared to patients without de novo DSAs. The association between de novo DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis. Conclusions: Our study suggested that de novo DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of de novo DSAs may be beneficial as noninvasive biomarker-guided risk stratification.