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

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.
Adult ; Biomarkers/blood ; Biopsy ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Hypertension, Portal/*blood/complications/mortality ; Intercellular Signaling Peptides and Proteins/*blood ; Liver/blood supply/pathology ; Liver Cirrhosis/*blood/etiology/mortality/pathology ; Male ; Middle Aged ; Portal Pressure ; Prognosis ; Proportional Hazards Models ; Prospective Studies

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

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody.
Acute Lung Injury* ; Anoxia ; Antibodies ; Blood Transfusion ; Catheters ; Cholecystitis ; Cyanosis ; Hemoptysis ; Humans ; Leukocytes ; Liver Cirrhosis ; Male ; Mortality ; Oxygen ; Plasma* ; Pulmonary Edema ; Tachycardia ; Tachypnea ; Thorax

The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions.
Alanine Transaminase/blood ; Alkaline Phosphatase/blood ; Animals ; Antigens, Differentiation/biosynthesis ; Aspartate Aminotransferases/blood ; Bone Marrow Cells/cytology ; *Bone Marrow Transplantation ; Cell Differentiation ; Cell- and Tissue-Based Therapy ; Cells, Cultured ; Collagen/metabolism ; Female ; Granuloma/parasitology/pathology ; Hepatocyte Growth Factor/pharmacology ; Hepatocytes/*cytology ; Liver/parasitology/pathology ; Liver Cirrhosis/parasitology/pathology/*therapy ; Male ; Mice ; Mice, Inbred BALB C ; Schistosoma mansoni/pathogenicity ; Schistosomiasis mansoni/mortality/*therapy ; *Stem Cell Transplantation ; Stem Cells/cytology

Acute variceal bleeding could be a fatal complication in patients with liver cirrhosis. In patients with decompensated liver cirrhosis accompanied by ascites or hepatic encephalopathy, acute variceal bleeding is associated with a high mortality rate. Therefore, timely endoscopic hemostasis and prevention of relapse of bleeding are most important. The treatment goals for acute variceal bleeding are to correct hypovolemia; achieve rapid hemostasis; and prevent early rebleeding, complications related to bleeding, and deterioration of liver function. If variceal bleeding is suspected, treatment with vasopressors and antibiotics should be initiated immediately on arrival to the hospital. Furthermore, to obtain hemodynamic stability, the hemoglobin level should be maintained at >8 g/dL, systolic blood pressure >90 to 100 mm Hg, heart rate <100/min, and the central venous pressure from 1 to 5 mm Hg. When the patient becomes hemodynamically stable, hemostasis should be achieved by performing endoscopy as soon as possible. For esophageal variceal bleeding, endoscopic variceal ligation is usually performed, and for gastric variceal bleeding, endoscopic variceal obturation is performed primarily. If it is considered difficult to achieve hemostasis through endoscopy, salvage therapy may be carried out while keeping the patient hemodynamically stable.
Anti-Bacterial Agents ; Ascites ; Blood Pressure ; Central Venous Pressure ; Endoscopy ; Esophageal and Gastric Varices* ; Heart Rate ; Hemodynamics ; Hemorrhage ; Hemostasis ; Hemostasis, Endoscopic ; Hepatic Encephalopathy ; Humans ; Hypovolemia ; Ligation ; Liver ; Liver Cirrhosis ; Mortality ; Recurrence ; Salvage Therapy

BACKGROUND/AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. METHODS: In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. RESULTS: Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16+/-5 to 14+/-10 (mean +/- SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (> or =2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). CONCLUSIONS: Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Hepatitis B/complications/*drug therapy ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Humans ; Lamivudine/*therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/mortality ; Male ; Middle Aged ; Odds Ratio ; Organophosphonates/*therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Survival Rate

PURPOSE: Refractory ascites (RA) is closely related to a high morbidity and mortality. In this study, we investigated predictors of RA development in patients with hepatitis B virus (HBV)-related cirrhosis who were hospitalized to control ascitic decompensation, and determined predictors for survival in patients who experienced RA. MATERIALS AND METHODS: We analyzed 199 consecutive patients with HBV-related cirrhosis who were hospitalized to control ascitic decompensation between January 1996 and December 2008. RESULTS: Multivariate analyses showed that only serum potassium at admission predicted RA development independently [p=0.013; hazard ratio (HR), 2.800; 95% confidence interval (CI), 1.166-6.722]. During the follow-up period, 16 (8.0%) patients experienced RA within 4.2 (range, 1.0-39.2) months after admission for controlling ascitic decompensation, and they survived a median of 8.7 (range, 3.9-51.3) months. Child-Pugh class and RA type were identified as independent prognostic factors affecting the survival in patients with RA (p=0.045; HR, 8.079; 95% CI, 1.231-67.984 and p=0.013; HR, 14.510; 95% CI, 1.771-118.874, respectively). CONCLUSION: Serum potassium was an independent predictor of RA development in patients with HBV-related cirrhosis who were hospitalized to control ascitic decompensation. After RA development, Child-Pugh class and RA type were independent predictors for survival.
Adult ; Aged ; Ascites/complications/*diagnosis/mortality ; Female ; Hepatitis B, Chronic/complications/mortality/*therapy ; Hospitalization ; Humans ; Liver Cirrhosis/complications/mortality/*therapy ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Potassium/blood ; Prognosis ; Retrospective Studies ; Treatment Outcome

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) has been known to greatly influence the survival rate of patients with liver cirrhosis. However, the factors that affect the survival rate in patients with SBP need to be clarified. METHODS: This study enrolled 95 liver cirrhosis patients diagnosed with SBP. The laboratory findings of their serum and ascitic fluid were examined and the characteristics of the isolated microorganisms in their peritoneal fluid were analyzed. RESULTS: The proportion of patients with culture-positive SBP was 41.1%, and 47 microorganisms were isolated from the ascitic fluid. The proportions of cultured bacteria that were Gram negative and Gram positive were 57.4% and 40.4%, respectively. The proportions of Escherichia coli, Klebsiella species, and Streptococcus species were 25.5%, 19.1%, and 19.1%, respectively. Enterococcus species represented 12.8% of the microorganisms cultured. The overall survival rates at 6, 12, and 24 months were 44.5%, 37.4%, and 32.2%, respectively. There was no relationship between the bacterial factors and the survival rate in SBP. Multivariate analysis revealed that the presence of hepatocellular carcinoma (HCC; P=0.001), higher serum bilirubin levels (> or =3 mg/dL, P=0.002), a prolonged serum prothrombin time (i.e., international normalized ratio >2.3, P<0.001), renal dysfunction (creatinine >1.3 mg/dL, P<0.001), and lower glucose levels in the ascitic fluid (<50 mg/dL, P<0.001) were independent predictive factors of overall survival rate. CONCLUSIONS: HCC, higher serum bilirubin levels, a prolonged serum prothrombin time, renal dysfunction, and lower ascitic glucose levels are associated with higher mortality rates in cirrhotic patients with SBP.
Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Ascitic Fluid/metabolism/microbiology ; Bilirubin/blood ; Carcinoma, Hepatocellular/complications/diagnosis ; Creatinine/blood ; Female ; Glucose/analysis ; Gram-Negative Bacteria/isolation & purification ; Gram-Positive Bacteria/isolation & purification ; Humans ; Liver Cirrhosis/complications/*mortality ; Liver Neoplasms/complications/diagnosis ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Peritonitis/complications/*diagnosis/drug therapy ; Prognosis ; Prothrombin Time ; Survival Rate

BACKGROUND/AIMS: Variceal rupture is the most common cause of upper gastrointestinal bleeding (UGIB) in cirrhotic patients and is well investigated. However, there are few documented studies on nonvariceal UGIB (NVUGIB) in these patients. This study was conducted to evaluate clinical features, in-hospital mortality rate and factors associated with mortality in cirrhotic patients with NVUGIB. MATERIALS AND METHODS: Among 399 cirrhotic patients who presented UGIB at Gyeongsang National University Hospital during 5 years since January 2007, patients with NVUGIB were selected by retrospective review of medical records. The patients' clinical and endoscopic findings, treatment outcomes, in-hospital mortality rates and its risk factors were investigated. RESULTS: NVUGIB was documented in 83 patients (20.8%). Mean age was 60.7+/-9.7 years, 85.5% was male. Child-Pugh class was A or B in 88%. Initial hemodynamic instability was reported in 25.3%, and 65.1% required blood transfusions. The major bleeding source was peptic ulcer 95.2% (79/83), and 44.6% (37/83) had endoscopic high risk bleeding stigmata and required endoscopic hemostasis. Rebleeding rate was 7.2% and in-hospital mortality rate was 8.4%. Hemodynamic instability (71.4% vs. 22.4%, P=0.013) and rebleeding (57.1% vs. 2.6%, P=0.000) were more frequent in the mortality group compared to the survival group. Hemodynamic instability was the risk factor for mortality at univariate and multivariate analyses. CONCLUSIONS: NVUGIB accounted for 20.8% of UGIB in liver cirrhosis and its development was not related to liver function. Peptic ulcer was the major cause and 45% required endoscopic hemostasis. It's in-hospital mortality rate was 8.4%, and hemodynamic instability was an independent risk factor of mortality in NVUGIB.
Blood Transfusion ; Christianity ; Hemodynamics ; Hemorrhage* ; Hemostasis, Endoscopic ; Hospital Mortality ; Humans ; Liver Cirrhosis* ; Liver* ; Male ; Medical Records ; Mortality ; Peptic Ulcer ; Retrospective Studies ; Risk Factors ; Rupture