Mapping the incidence of drug-induced liver injury: A systematic review and meta-analysis.

OBJECTIVES: Drug-induced liver injury (DILI) is an increasing etiology of liver dysfunction, with various incidence worldwide. To better understand the disease burden and establish appropriate preventive and treatment strategies, a systematic review and meta-analysis was conducted. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies on the incidence of DILI published up to June 1, 2022. According to the predefined criteria, only population-based studies were included. Incidence was presented as cases per 100 000 person-years with 95% confidence interval (CI) using a random-effects model. RESULTS: A total of 14 studies were included. The overall incidence of DILI was 4.94 per 100 000 person-years (95% CI 4.05-5.83). Time-based cumulative meta-analysis suggested that the incidence of DILI increased over time since 2010. The incidence varied by regions, with Asia having the highest incidence of 17.82 per 100 000 person-years (95% CI 6.26-29.38), while North America having the lowest incidence of 1.72 per 100 000 person-years (95% CI 0.48-2.95). All studies reported a higher incidence of DILI in the elderly but comparable incidences between male and female (3.42 per 100 000 person-years vs 4.64 per 100 000 person-years). CONCLUSIONS: The global incidence of DILI has been increasing since 2010, with the highest incidence in Asia. Understanding the epidemiological characteristics of DILI helps establish specific strategies to deal with this emerging health problems.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease: An extended study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.

BACKGROUND: The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. METHODS: We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. RESULTS: Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. CONCLUSIONS: Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.

New-onset hyperglycemia immediately after liver transplantation: A national survey from China Liver Transplant Registry.

BACKGROUND: New-onset hyperglycemia (NOH) is a common phenomenon after liver transplantation (LT), but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT. METHODS: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent. RESULTS: Of 3339 liver recipients, 1416 (42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis, and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients (P < 0.05). The independent risk factors of NOH were donor warm ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage (P < 0.05). Liver enzymes (alanine aminotransferase and gamma-glutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH (P < 0.001). CONCLUSIONS: NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.

Author Correction: Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit.

Correction to: Emerging Microbes & Infections (2016) 5:e1; https://doi.org/10.1038/emi.2016.1 ; Article published online 6 January 2016.

Percutaneous liver biopsy: retrospective study of primary and secondary hepatic lymphoma in twenty-one patients.

BACKGROUND: Hepatic lymphoma (HL) is categorized as primary and secondary hepatic lymphoma (PHL and SHL). This disorder can present as hepatic mass or mass-like lesion. Chemotherapy often is the first line treatment for patients with HL. Thus, an accurate pre-management histological diagnosis is essential to potentially improve clinical outcomes. The present study was to explore the prevalence of HL in ultrasound guided liver biopsies for hepatic mass or mass-like lesions, to investigate HL associated clinicopathological features, to raise the awareness of early recognition and proper diagnosis of this entity, and to assess specimen adequacy in needle core biopsy. METHODS: Twenty-one cases of HL were enrolled. Clinical and pathological characteristics were evaluated, quality of biopsies was assessed and pertinent literature was reviewed. RESULTS: HL was diagnosed in 0.94% of 2242 liver biopsy cases with ambiguous clinical presentation, laboratory tests and image studies. There were two cases of PHL (0.09%), and nineteen cases of SHL (0.85%). Histopathologically, diffuse large B-cell lymphoma was the most common type, followed by B-cell lymphoma not otherwise specified, T-cell lymphoma, Hodgkin's lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Additionally, three lymphocytic infiltration patterns were documented microscopically. The nodular infiltration was the most common type. CONCLUSIONS: HL is a rare entity and histopathology along with ancillary tests remains the only way to make the diagnosis. Clinicians' awareness of this entity and early liver biopsy are essential in patient management.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. METHODS: A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. RESULTS: The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). CONCLUSION: ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.