Prediction of biochemical nonresolution in patients with chronic drug-induced liver injury: A large multicenter study.

BACKGROUND AND AIMS: To clarify high-risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI. APPROACH AND RESULTS: Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high-risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3-fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR-6) with a concordance index of 0.824 (95% CI, 0.798-0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort. CONCLUSIONS: Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR-6 model provides an easy-to-use approach to assess the outcome of chronic DILI.

Idiopathic acute superior mesenteric venous thrombosis after renal transplantation: A case report.

BACKGROUND: Acute superior mesenteric venous thrombosis (MVT) is a rare condition associated with a high mortality rate. The treatment strategy for MVT is clinically challenging due to its insidious onset and rapid development, especially when accompanied by kidney transplantation. CASE SUMMARY: Here we present a rare case of acute MVT developed 3 years after renal transplantation. A 49-year-old patient was admitted with acute abdominal pain and diagnosed as MVT with intestinal necrosis. An emergency exploratory laparotomy was performed to remove the infarcted segment of the bowel. Immediate systemic anticoagulation was also initiated. During the treatment, the patient experienced bleeding, anastomotic leakage, and sepsis. However, after aggressive treatment was administered, all thrombi were completely resolved, and the patient recovered with his renal graft function unimpaired. CONCLUSION: The present case suggests that accurate diagnosis and timely surgical treatment are important to improve the survival rate of MVT patients. Bleeding with anastomotic fistula needs to be treated with caution because of grafts. Also, previously published cases of mesenteric thrombosis after renal transplantation were reviewed.

Comparison of emergency cholecystectomy and delayed cholecystectomy after percutaneous transhepatic gallbladder drainage in patients with acute cholecystitis: a systematic review and meta-analysis.

Laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) are common treatments for patients with acute cholecystitis. However, the safety and efficacy of emergency laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC) after PTGBD in patients with acute cholecystitis remain unclear. The PubMed, EMBASE, and Cochrane Library databases were searched through October 2019. The quality of the included nonrandomized studies was assessed using the Methodological Index for Nonrandomized Studies (MINORS). The meta-analysis was performed using STATA version 14.2. A random-effects model was used to calculate the outcomes. A total of fifteen studies involving 1780 patients with acute cholecystitis were included in the meta-analysis. DLC after PTGBD was associated with a shorter operative time (SMD - 0.51; 95% CI - 0.89 to - 0.13; P = 0.008), a lower conversion rate (RR 0.43; 95% CI 0.26 to 0.69; P = 0.001), less intraoperative blood loss (SMD - 0.59; 95% CI - 0.96 to - 0.22; P = 0.002) and longer time of total hospital stay compared to ELC (SMD 0.91; 95% CI 0.57-1.24; P < 0.001). There was no difference in the postoperative complications (RR 0.68; 95% CI 0.48-0.97; P = 0.035), biliary leakage (RR 0.65; 95% CI 0.34-1.22; P = 0.175) or mortality (RR 1.04; 95% CI 0.39-2.80; P = 0.933). Compared to ELC, DLC after PTGBD had the advantages of a shorter operative time, a lower conversion rate and less intraoperative blood loss.

A perspective of the relationship of serum HBV DNA and HBsAg apportioned by the same hepatic parenchyma cell volume with inflammation in the natural history of chronic hepatitis B.

BACKGROUND: This study aimed to investigate the dynamic changes of serum HBV DNA and hepatitis B surface antigen (HBsAg) titers apportioned by the same hepatic parenchyma cell volume (HPCV) at different liver histological inflammation grades in the natural history of chronic hepatitis B (CHB). METHODS: The serum HBV DNA and HBsAg titers were detected by real-time polymerase chain reaction and electrochemiluminescence, separately, in CHB patients without any treatment. The serum HBV DNA levels and HBsAg titers apportioned by the same HPCV were figured out based on sphere geometry theory. In addition, the differences of HBV DNA levels and HBsAg titers apportioned by the same HPCV in different liver inflammation grades were further assessed based on statistical analysis. RESULTS: There was no difference of serum HBV DNA levels or HBsAg titers before apportioned by the same HPCV in liver inflammation grades 1-4, but significant differences were observed after apportion in CHB patients (HBV DNA: P=0.101; HBsAg: P=0.211 & HBV DNA apportioned by HPCV: P<0.001; HBsAg apportioned by HPCV: P<0.001). No correlation was observed between HBV DNA levels and liver inflammation grades (r=0.083, P=0.186), or between HBsAg titers and liver inflammation grades (r=0.083, P=0.078). A significant correlation was observed between HBV DNA levels apportioned by HPCV and liver inflammation grades (r=0.249, P<0.001), and obvious correlation of HBsAg titers apportioned by HPCV and liver inflammation grades was also found in CHB patients (r=0.554, P<0.001). CONCLUSIONS: These results suggest that the levels of serum HBV DNA and HBsAg apportioned by the same HPCV are correlated with the severity of liver histological inflammation grade in the natural history of CHB.

Risk factors analysis for surgical site infection following elective colorectal resection: a retrospective regression analysis.

BACKGROUND: A surgical site infection (SSI) is a major post-operative complication from elective colorectal surgery; however, few studies have focused on evaluating the risk factors for SSI. This study aimed to analyze the relative correlation of medical and environmental factors as well as patient-related factors that contribute to the incidence of all types of SSI. METHODS: A retrospective search for eligible patients was conducted using the patient database of the Gastrointestinal Surgery Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2011 to August 2017. Pre-operative demographic and surgical data were extracted and recoded according to the study protocol. Univariate and multivariate analyses were performed to clarify factors affecting the incidence of SSI. Propensity analysis was conducted to minimize bias in the demographic characteristics to explore the prophylactic effect of pre-operative administration of oral antibiotics. RESULTS: Univariate analysis of the baseline characteristics revealed that younger age (odds ratio [OR]: 0.378; 95% confidence interval [CI]: 0.218-0.657) and pre-operative oral antibiotic use (OR: 0.465; 95% CI: 0.255-0.850) were protective factors, while pre-operative anemia (OR: 4.591; 95% CI: 2.567-8.211), neoadjuvant chemotherapy history (OR: 2.398; 95% CI: 1.094-5.256), and longer surgical duration (OR: 2.393; 95% CI: 1.349-4.246; P = 0.002) were identified as risk factors for SSI. Multivariate analysis indicated that age (P = 0.003), surgical duration (P = 0.001), and pre-operative oral antibiotic use (P < 0.001) were independent factors that affect the incidence of SSI. Furthermore, a propensity-matched analysis confirmed the protective effect of oral antibiotic use, with a 1-day course of oral antibiotic producing a similar effect to a 3-day course. CONCLUSIONS: Age, surgical duration, and pre-operative oral antibiotic use were associated with the incidence of SSI. However, pre-operative oral antibiotic use was the only controllable factor. From the results of our study, pre-operative oral antibiotic use is recommended before elective colorectal surgery and a 1-day course is enough to provide the protective effect.

KCNK levels are prognostic and diagnostic markers for hepatocellular carcinoma.

Two-pore-domain (KCNK, K2P) K+ channels are transmembrane protein complexes that control the flow of ions across biofilms, which underlie many essential cellular functions. Because KCNK family members are known to contribute to tumorigenesis in various types of cancer, we hypothesized that they might be differentially expressed in hepatocellular carcinoma (HCC) cells as compared to healthy tissue and serve as diagnostic or prognostic biomarkers. We tested this hypothesis through bioinformatic analyses of publicly available data for the expression of various KCNK subunits in HCC. We observed reduced expression of KCNK2, KCNK15, and KCNK17 in liver cancer, as well as overexpression of KCNK9, all of which correlated with a better prognosis for HCC patients per survival analyses. Moreover, ROC curves indicated that KCNK2, KCNK9, KCNK15, and KCNK17 levels could be used as a diagnostic biomarker for HCC. Finally, our western blot and qRT-PCR results were consistent with those obtained from bioinformatic analyses. Taken together, these results suggest that KCNK2, KCNK9, KCNK15, and KCNK17 could serve as potential diagnostic and prognostic biomarkers of HCC.

Sorafenib-induced acute-on-chronic liver failure in a patient with hepatocellular carcinoma after transarterial chemoembolization and radiofrequency ablation: A case report.

Comprehensive treatments together with sorafenib provide a survival benefit for patients with advanced hepatocellular carcinoma (HCC). Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct entity; however, only few cases induced by sorafenib have been reported to date. We herein present a rare case of ACLF in a patient under treatment with sorafenib. A 63-year-old woman who suffered from hepatitis B for 10 years was admitted to our hospital. A computed tomography (CT) scan led to a diagnosis of HCC in the V/VIII hepatic segment, with invasion of the middle hepatic and the right portal veins. The patient received multidisciplinary treatment, including transarterial chemoembolization, radiofrequency ablation and sorafenib. Two months after sorafenib treatment, the patient was readmitted due to progressive jaundice and ACLF was diagnosed by liver biopsy shortly thereafter. Although aggressive treatment was administered, the patient succumbed to the disease following rapid deterioration of her clinical condition. The majority of patients with HCC have underlying liver disease and combination therapy with sorafenib should be administered with caution, as it may increase the risk of severe hepatotoxicity. The present case suggests that patients treated with sorafenib may require a dose reduction following interventional treatment.

Complications Following Radiofrequency Ablation of Benign Thyroid Nodules: A Systematic Review.

OBJECTIVE: This systematic review examined whether radiofrequency ablation (RFA) is a safe treatment modality for benign thyroid nodules (BTNs). DATA SOURCES: PubMed, Embase, and the Cochrane Library database were searched for articles that (a) targeted human beings and (b) had a study population with BTNs that were confirmed by fine-needle aspiration cytology and/or core needle biopsy. STUDY SELECTION: Thirty-two studies relating to 3409 patients were included in this systematic review. RESULTS: Based on literatures, no deaths were associated with the procedure, serious complications were rare, and RFA appears to be a safe and well-tolerated treatment modality. However, a broad spectrum of complications offers insights into some undesirable complications, such as track needle seeding and Horner syndrome. CONCLUSIONS: RFA appears to be a safe and well-tolerated treatment modality for BTNs. More research is needed to characterize the complications of RFA for thyroid nodules.

Inhibition of mTOR promotes hyperthermia sensitivity in SMMC-7721 human hepatocellular carcinoma cell line.

The mammalian target of rapamycin (mTOR) is a critical mediator of the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway, and mTOR activity is induced following heat shock. Thermotherapy is used to treat hepatocellular carcinoma (HCC). However, the role of mTOR in modulating thermosensitivity in HCC has yet to be elucidated. In the present study, the antisense plasmid pEGFP-C1-mTOR was transfected into SMMC-7721 cells, and the expression levels of mTOR were analyzed by reverse transcription-polymerase chain reaction and western blot analysis. The thermal responses of the transfected cells were also examined. The results revealed that SMMC-7721 cells were sensitive to heat treatment, and cell viability was significantly inhibited following hyperthermia treatment (P<0.01). The mRNA and protein expression levels of mTOR decreased post-transfection. Cell proliferation, colony-forming ability and motility were all significantly decreased following hyperthermia treatment in the transfected cells. Flow cytometry analysis demonstrated that apoptosis was significantly increased following treatment (P<0.01). The number of cells in S phase was increased, and the cell cycle was arrested in S phase. In conclusion, inhibition of mTOR increased the thermosensitivity of SMMC-7721 cells by increasing cellular apoptosis and inducing S phase arrest.

Beneficial effect of splenic artery ligation on bacterial translocation after major liver resection in rats.

OBJECTIVE: In major liver resection, bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infection. This study was designed to investigate the effects of splenic artery ligation on bacterial translocation after major liver resection. MATERIALS AND METHODS: Rats were divided into three groups: the sham operation group (SO group), the two-thirds partial hepatectomy group (PHx group) and the two-thirds partial hepatectomy plus splenic artery ligation group (PHx+Sp group). Bacterial translocation, endotoxemia, d-lactic acid and intestinal histology were analyzed among three groups. RESULTS: The rate of bacterial translocation was higher in the PHx rats than in the SO rats (65.0% vs. 6.67%; P=0.001), so that in the PHx+Sp rats (25.0%; P=0.011). Endotoxemia was not evident in the SO rats (0pg/ml) and blood endotoxin levels decreased in the PHx+Sp rats (1.47pg/ml) compared with the PHx rats (4.05pg/ml, P<0.001). d-lactic acid was also higher in both the PHx and PHx+Sp rats compared with the SO rats (39.09mg/ml, 23.36mg/ml, and 1.68mg/ml; P<0.01). CONCLUSION: Splenic artery ligation enhanced intestinal barrier function and diminished blood endotoxin levels and bacterial translocation in rats with major liver resection.