Han Deng

Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma: A systematic review and meta-analysis of observational studies

Background and aims Neutrophil to lymphocyte ratio (NLR) is an inflammatory-based marker. A systematic review and meta-analysis was performed to explore the prognostic role of NLR in patients with hepatocellular carcinoma (HCC). Results Overall, 598 papers were identified, of which 90 papers including 20,475 HCC patients were finally included. Low baseline NLR was significantly associated with better overall survival (HR = 1.80, 95% CI: 1.59–2.04, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.80–2.76, p < 0.00001). Low post- treatment NLR was significantly associated with better overall survival (HR = 1.90, 95% CI: 1.22–2.94, p = 0.004). Decreased NLR was significantly associated with overall survival (HR = 2.23, 95%CI: 1.83–2.72, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.83–2.72, p < 0.00001). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses. Materials and Methods All relevant literatures were identified via PubMed, EMBASE, and Cochrane library databases. Hazard ratio (HR) with 95% confidence interval (95%CI) was calculated. Subgroup meta-analyses were performed according to the treatment options, NLR cut-off value ranges, and regions. Conclusions NLR should be a major prognostic factor for HCC patients. NLR might be further incorporated into the prognostic model of HCC.

Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study

Background Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. Material/Methods All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. Results A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506–0.6 and 0.539–0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601–0.664 and 0.596–0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627–0.69 and 0.607–0.692, respectively. Conclusions APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis.

Epidemiology, Risk Factors, and In-Hospital Mortality of Venous Thromboembolism in Liver Cirrhosis: A Single-Center Retrospective Observational Study

Background Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be increased in liver cirrhosis. We conducted a single-center study to explore the epidemiology, risk factors, and in-hospital mortality of VTE in Chinese patients with liver cirrhosis. Material/Methods All patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and December 2013 were retrospectively included. Results Of 2006 patients with liver cirrhosis included, 9 patients were diagnosed with or developed VTE during hospitalization, including 5 patients with a previous history of DVT, 1 patient with either a previous history of DVT or new onset of PE, and 3 patients with new onset of VTE (PE, n=1; DVT, n=2). Risk factors for VTE included a significantly higher proportion of hypertension and significantly higher red blood cells, hemoglobin, alanine aminotransferase, aspartate aminotransferase, prothrombin time (PT), international normalized ratio (INR), D-dimer, and Child-Pugh scores. The in-hospital mortality was significantly higher in patients with VTE than those without VTE (33.3% [3/9] versus 3.4% [67/1997], P<0.001). Conclusions VTE was observed in 0.4% of patients with liver cirrhosis during hospitalization and it significantly increased the in-hospital mortality. Elevated PT/INR aggravated the risk of VTE.

Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study

Objective: A retrospective study was performed to compare the difference in platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), between cirrhotic patients with and without acute upper gastrointestinal bleeding (AUGIB) or acute oesophageal variceal bleeding (AEVB). Methods: Between January 2012 and June 2014, a total of 1734 cirrhotic patients were enrolled and were classified into ‘AUGIB’ (n = 497) and ‘no AUGIB’ (n = 1237) groups according to their disease history. They were further divided into ‘AEVB’ (n = 297) and ‘no AEVB’ (n = 1259) groups according to the endoscopic findings. Additionally, 178 patients with AUGIB were not assigned to either the ‘AEVB’ or ‘no AEVB’ groups due to the absence of any endoscopic findings. Results: Compared with the ‘no AUGIB’ group, the ‘AUGIB’ group had similar PLT (99.99 ± 89.90 vs.101.47 ± 83.03; P = 0.734) and APTT (42.96 ± 15.20 vs.43.77 ± 11.01; P = 0.219), but significantly higher PT (17.30 ± 5.62 vs.16.03 ± 4.68; P < 0.001) and INR (1.45 ± 0.69 vs.1.31 ± 0.59; P < 0.001). A lower PT was independently associated with the absence of AUGIB (OR = 0.968; 95% CI: 0.942–0.994). Compared with the ‘no AEVB’ group, the ‘AEVB’ group had significantly lower PLT (86.87 ± 62.14 vs.101.74 ± 83.62; P = 0.004) and APTT (40.98 ± 7.9 vs.43.72 ± 10.97; P < 0.001), but similar PT (16.53 ± 3.71 vs.16.04 ± 4.68; P = 0.088) and INR (1.35 ± 0.41 vs.1.31 ± 0.59; P = 0.225). A higher PLT was independently associated with the absence of AEVB (OR = 1.004; 95% CI: 1.002–1.006; P = 0.001). Conclusions: PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.

Supersonic shear imaging for the diagnosis of liver fibrosis and portal hypertension in liver diseases: a meta-analysis

ABSTRACT Background and aims: The meta-analysis aimed to summarize the technical success rate of supersonic shear imaging (SSI) and to evaluate the diagnostic performance of liver and spleen stiffness measurement (LSM and SSM) with SSI for the detection of liver fibrosis, portal hypertension, and gastroesophageal varices in liver diseases. Methods: PubMed, EMBASE, and Cochrane Library databases were searched. Technical success rate of SSI was pooled. Area under curve (AUC), sensitivity, and specificity with corresponding 95% confidence interval (CI) were calculated. Results: Included studies regarding the diagnostic performance of SSI for liver fibrosis, portal hypertension, and esophageal varices numbered 28, 4, and 4 respectively. The pooled technical success rates of LSM and SSM were 95.3% and 75.5%, respectively. The AUC, sensitivity, and specificity of LSM/SSM for different stages of liver fibrosis were 0.85–0.94, 0.7–0.89, and 0.82–0.92, respectively. The AUC, sensitivity, and specificity of LSM were 0.84 (95%CI = 0.8–0.86), 0.79 (95%CI = 0.7–0.85), and 0.82 (95%CI = 0.72–0.88) for clinically significant portal hypertension, 0.85 (95%CI = 0.82–0.88), 0.8 (95%CI = 0.68–0.88), and 0.8 (95%CI = 0.6–0.92) for any varices, and 0.86 (95%CI = 0.83–0.89), 0.86 (95%CI = 0.76–0.92), and 0.61 (95%CI = 0.35–0.83) for high-risk varices, respectively. Conclusions: LSM with SSI had a high diagnostic accuracy for liver fibrosis, but a moderate diagnostic accuracy for portal hypertension and esophageal varices.

Association Between Hepatocellular Carcinoma and Type 2 Diabetes Mellitus in Chinese Hepatitis B Virus Cirrhosis Patients: A Case-Control Study

Background Whether the presence of type 2 diabetes mellitus (T2DM) increases the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) cirrhosis patients is controversial. We conducted a retrospective case-control study to evaluate this issue. Material/Methods We considered all patients diagnosed with HBV-related liver cirrhosis at our hospital from July 2011 to June 2014. The case (n=91) and control (n=91) groups were HBV cirrhosis patients with and without T2DM, respectively. They were matched at a ratio of 1: 1 according to the individual age (±2 years) and same sex and Child-Pugh score. Results None of the baseline data were significantly different between the 2 groups. The percentage of HCC was similar between the 2 groups (case versus control group: 34.1% versus 46.2%, P=0.13). In the case group, sex (P=0.002), alkaline phosphatase (P<0.001), γ-glutamine transferase (P=0.001), and sodium (P=0.003) were associated with the risk of HCC. In the control group, platelet (P=0.041), alanine aminotransferase (P=0.034), aspartate aminotransferase (P=0.026), alkaline phosphatase (P<0.001), and γ-glutamine transferase (P<0.001) were associated with the risk of HCC. Conclusions T2DM may not be a risk factor for the presence of HCC in HBV cirrhosis.

Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

Background Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. Material/Methods All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152–61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247–276.949; clinically significant PVST: OR=40.415, 95%CI=3.895–419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953–0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895–0.980; clinically significant PVST: OR=0.935, 95%CI=0.891–0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909–0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. Conclusions Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

Knowledge about non-invasive diagnostic tests for varices in liver cirrhosis: A questionnaire survey to the Gastroenterology Branch of the Liaoning Medical Association, China

Background and aims: Due to the invasiveness of upper gastrointestinal endoscopy, non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies. A questionnaire survey, which was aimed at understanding the current knowledge about non-invasive diagnostic tests for varices in liver cirrhosis, was distributed among the members of Gastroenterology Branch of the Liaoning Medical Association. Methods: A questionnaire assessing the knowledge about non-invasive diagnostic tests for varices was sent to 42 members who participated in the entire ninth committee. They were from 33 hospitals in 13 cities of Liaoning Province, China. Results: Overall, 97.6% (41/42) of participants responded to the questionnaire. A majority of participants were chief physicians (85.4%), had >20 years of experience in clinical work of digestive diseases (80.5%) and worked at tertiary hospitals (97.6%). In 46.3% of participants’ departments, there were >200 patients with liver cirrhosis and gastroesophageal varices admitted every year. In 90.2% of participants’ departments, upper gastrointestinal endoscopy was regularly employed for the diagnosis of gastroesophageal varices. Only six (15%) participants often used non-invasive diagnostic tests for varices in clinical practice. Thirty (75%) participants knew at least one non-invasive diagnostic test for varices. The knowledge of at least one non-invasive diagnostic test was significantly associated with the number of cirrhotic patients with varices (P = 0.038) or the regular use of gastrointestinal endoscopy to diagnose varices (P = 0.022). Conclusions: This questionnaire survey suggested that non-invasive diagnostic tests for varices in liver cirrhosis were rarely or never used in clinical practices in Liaoning Province, China. Reliable, non-invasive indexes should be further explored in a well-designed multi-center observational study.

Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review

ABSTRACT Backgrounds: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. Aims: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). Methods: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched. Demographic, clinical, and survival data were extracted and pooled. Factors associated with worse outcomes were calculated. For the proportion meta-analyses, the data were pooled by using a random-effects model. Results: Overall, 21,027 articles were retrieved, of which 625 were finally included. There was a predominance of female and older patients. The proportion of liver transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly associated with an increased risk of death/liver transplantation in TCM-ILI patients. The proportion of TCM-ILI in all DILI was 25.71%. The proportion was gradually increased with year. Conclusions: Our work summarises current knowledge regarding clinical presentation, disease course, and prognosis of TCM-ILI. TCM can result in hepatotoxicity, even death or necessitate life-saving liver transplantation. Governmental regulation of TCM products should be strictly established.

Ischemic stroke in liver cirrhosis: epidemiology, risk factors, and in-hospital outcomes

Background and aims Patients with cirrhosis are reportedly more prone to develop hemorrhagic stroke, thereby increasing the risk of death. However, the effect of ischemic stroke on liver diseases remains unclear. In addition, few studies have explored the risk factors for ischemic stroke in patients with liver cirrhosis. Our study aimed to explore the epidemiology, risk factors, and in-hospital outcomes of ischemic stroke in a large cohort of hospitalized patients with cirrhosis. Patients and methods In this single-center observational study, we retrospectively reviewed the medical records of patients with liver cirrhosis admitted to our hospital from January 2011 to June 2014. A diagnosis of ischemic stroke was further identified. Results Of the 2444 patients with liver cirrhosis, 160 had ischemic stroke, including 128 patients with previous ischemic stroke and 32 patients with new-onset ischemic stroke during their hospitalizations. Compared with patients with cirrhosis without ischemic stroke, those with ischemic stroke were significantly older; had a significantly higher proportion of arterial hypertension and a significantly lower proportion of hepatitis B virus infection; had significantly higher white blood cell, platelet, blood urea nitrogen, and triglyceride levels; and had significantly lower alanine aminotransferase and aspartate aminotransferase levels and prothrombin time. The in-hospital mortality was significantly higher in patients with ischemic stroke than in those without [8.80% (14/160) vs. 3.2% (72/2284), P=0.001]. Conclusion Ischemic stroke was often observed in patients with cirrhosis, and it significantly increased the in-hospital mortality. The association of inflammation, coagulation disorders, and viral hepatitis with development of ischemic stroke in liver cirrhosis should be further evaluated in prospective cohort studies.