OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular ; blood ; diagnosis ; virology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; blood ; diagnosis ; virology ; Mass Spectrometry ; Metabolome ; Metabolomics ; ROC Curve

BACKGROUND AND PURPOSE: To test whether alcohol intake, both observational and estimated by genetic instruments, is associated with risk of ischemic and haemorrhagic stroke. METHODS: We used data from the Copenhagen City Heart Study 1991 to 1994 and 2001 to 2003, and the Copenhagen General Population Study 2003 to 2012 (n=78,546). As measure of alcohol exposure, self-reported consumption and genetic variation in alcohol metabolizing genes (alcohol dehydrogenase ADH1B and ADH1C) as instrumental variables were used. Stroke diagnoses were obtained from a validated hospital register. RESULTS: During follow-up 2,535 cases of ischemic and haemorrhagic stroke occurred. Low and moderate alcohol intake (1 to 20 drinks/week) was associated with reduced risk of stroke. The hazard ratios associated with drinking 1 to 6, 7 to 13, and 14 to 20 drinks/week were 0.84 (95% confidence interval [CI], 0.76 to 0.92), 0.83 (95% CI, 0.73 to 0.94), and 0.84 (95% CI, 0.73 to 0.97), respectively, compared with drinking < 1 drink/day. ADH1B and ADH1C genotypes were not associated with risk of stroke. Further analysis to test the included measures revealed that increasing alcohol intake (per 1 drink/day) was positively associated with risk of alcoholic liver cirrhosis, but not associated with risk of stroke, and that increasing blood pressure (per systolic 10 mm Hg) was not associated with risk of alcoholic liver cirrhosis, but positively associated with risk of stroke. CONCLUSIONS: Low and moderate self-reported alcohol intake was associated with reduced risk of stroke. The result was not supported by the result from the causal genetic analysis.
Alcohol Drinking ; Blood Pressure ; Diagnosis ; Drinking ; Follow-Up Studies ; Genetic Variation ; Genotype ; Heart ; Incidence ; Liver Cirrhosis, Alcoholic ; Oxidoreductases ; Prospective Studies ; Stroke*

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

BACKGROUND/AIMS: The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. METHODS: A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). RESULTS: The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). CONCLUSIONS: In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population.
Aspartate Aminotransferases ; Biomarkers* ; Biopsy ; Blood Platelets ; Coinfection ; Diagnosis ; Fibrosis* ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis C, Chronic ; Hepatitis* ; Hepatitis, Chronic ; Humans ; Liver ; Liver Cirrhosis ; Platelet Count ; Prothrombin Time ; Retrospective Studies

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Esophageal and Gastric Varices/complications/prevention & control ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Ultrasonography

We aimed to estimate the threshold level of glycosylated hemoglobin (HbA1c) for the fasting plasma glucose of 100 and 126 mg/dL in the Korean adult population, using the 2011 Korea National Health and Nutrition Examination Survey. A total of 4,481 participants over 19 years of age without diabetic medications and conditions to influence the interpretation of HbA1c levels, such as anemia, renal insufficiency, liver cirrhosis, and cancers, were analyzed. A point-wise area under the receiver operating characteristic curve was used to estimate the optimal HbA1c cutoff value. A HbA1c threshold of 6.35% was optimal for predicting diabetes with a sensitivity of 86.9% and a specificity of 99.1%. Furthermore, the threshold of HbA1c was 5.65% for prediabetes, with a sensitivity of 69.3% and a specificity of 71%. Further prospective studies are needed to evaluate the HbA1c cutoff point for diagnosing prediabetes and diabetes in the Korean population.
Adult ; Anemia ; Blood Glucose ; Diabetes Mellitus ; Diagnosis ; Fasting ; Hemoglobin A ; Hemoglobin A, Glycosylated* ; Humans ; Korea* ; Liver Cirrhosis ; Nutrition Surveys* ; Prediabetic State* ; Prospective Studies ; Renal Insufficiency ; ROC Curve ; Sensitivity and Specificity

BACKGROUND/AIMS: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). METHODS: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. RESULTS: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). CONCLUSIONS: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.
Aged ; Blood Platelets ; Critical Illness ; Female ; Gastrointestinal Hemorrhage/blood/diagnosis/*etiology/mortality ; Hospital Mortality ; Humans ; Intensive Care Units ; Liver Cirrhosis/blood/*complications/diagnosis/mortality ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Platelet Count ; Prognosis ; Republic of Korea ; Respiratory Tract Diseases/blood/diagnosis/*etiology/mortality ; Retrospective Studies ; Risk Factors ; Sepsis/blood/complications ; Time Factors

PURPOSE: The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis. MATERIALS AND METHODS: Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed. RESULTS: During a median follow-up of 24 (interquartile range, 13-36) months, 22 patients (22.7%) died. The area under the receiver operating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG < or =17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG < or =17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly, for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes. CONCLUSION: HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.
Adult ; Aged ; Ascites/mortality ; Female ; Hepatic Veins/*physiopathology ; Humans ; Kaplan-Meier Estimate ; Liver Cirrhosis/blood/complications/diagnosis/*mortality/*physiopathology ; Liver Failure/diagnosis/*mortality/physiopathology ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Venous Pressure

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.
Biomarkers/*blood ; DNA, Viral/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/prevention & control ; Humans ; Liver Cirrhosis/etiology ; Organic Anion Transporters, Sodium-Dependent/genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Symporters/genetics

The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.
Acute Kidney Injury/complications/*diagnosis/drug therapy/pathology ; Biomarkers/blood ; Creatinine/blood ; Humans ; Liver Cirrhosis/*complications ; Prognosis ; Serum Albumin/therapeutic use ; Severity of Illness Index