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Objective: Patients with liver cirrhosis (LC) are at increased risk for bacterial infections. It is not fully understood how exposure to infections induces further development of hepatic encephalopathy (HE). This study estimated risks of infection associated with HE among patients with LC. Methods: A nested case-control study of 14,428 adult patients with LC was performed using the population-based Longitudinal Health Insurance Database 2000 in Taiwan. Cases were cirrhotic patients who developed HE during follow-up. Controls were matched to each case by age at LC diagnosis (±2 years), sex, Charlson Comorbid index score, year of LC, and follow-up time with a 1:1 ratio. A multivariate logistic regression model was used to determine and compare the odds of developing HE based on exposure to various risk factors, including site of infection, cirrhosis-related complications, Helicobacter pylori eradication therapy, and peptic ulcer bleeding. Patient survival was evaluated using the time-dependent Cox regression model. Results: Cirrhotic patients with HE (n = 714) and without HE (n = 714) were matched to compare risks. Infections and more frequent yearly infections were significantly associated with increased risk of HE. Independent predictors of HE included (aOR, 5.13; 95% CI, 3.03–8.69), sepsis (aOR, 2.54; 95% CI, 1.82–-3.53), and biliary tract infection (aOR, 2.03; 95% CI, 1.2–3.46), controlling for confounders. Conclusion: Frequent infections are associated with increased risk of HE in cirrhotic patients. More frequent exposure to infection increases the risk of HE and mortality rates. Appropriate prevention of infection and the use of antibiotics for cirrhotic patients at risk for HE are needed. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997–2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10–1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01–1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74–0.96, p = 0.009), and patients with alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65–2.26, p<0.001) had a statistically significant difference in the incidence of HCC. In conclusion, complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan compared with cirrhosis without complications. [ABSTRACT FROM AUTHOR]

Although a few studies have investigated the risks of peptic ulcer bleeding (PUB) in cirrhotic patients, large population-based studies on in-hospital and long-term reports on recurrent PUB in a cohort of cirrhotic patients are lacking. This 12-year nationwide cohort study aimed to investigate the risks of in-hospital and long-term rebleeding and mortality in cirrhotic patients and to identify possible risk factors. Patient data from 1997 to 2008 were extracted from the National Health Insurance Research Database in Taiwan. A total of 15,575 patients who were discharged with a diagnosis of PUB were identified after strict exclusions (n = 2889). Among them, patients with cirrhosis (n = 737) and those with chronic hepatitis (n = 1044) were compared to propensity-score matched normal controls at a ratio of 1:1. Accumulated in-hospital and long-term follow-up PUB-free survival rates were analyzed in patients with cirrhosis, patients with chronic hepatitis, and matched controls. Cox proportional hazards regression was used to identify each independent risk factor. Compared with matched controls, patients with cirrhosis exhibited a 2.62-fold (95% CI: 1.74–3.92) higher risk of developing in-hospital rebleeding, but the risk of long-term rebleeding was comparable between cirrhotic patients and matched controls (hazard ratio: 1.29, 95% CI: 0.8–2.09). On the other hand, no significant difference was observed in in-hospital and long-term rebleeding between chronic hepatitis patients and matched controls. We compared the survival rates of cirrhotic and chronic hepatitis patients to that of matched controls. After propensity score matching, both cirrhotic and chronic hepatitis patients showed significantly lower survival than the matched controls (P < 0.0001 and 0.033, respectively) during the 12-year follow-up period. However, in-hospital and long-term rebleeding rates were not significantly different between chronic hepatitis patients and matched controls (P = 0.251 and 0.474, respectively). In conclusion, liver cirrhosis increased health care expenses in patients with PUB and these patients exhibited higher recurrent bleeding rate than non-cirrhotic patients during hospitalization. Cirrhosis and chronic hepatitis are independently associated with an increased long-term mortality when compared with patients without liver disease. [ABSTRACT FROM AUTHOR]

Background & Aims Liver stiffness measurement ( LSM) using transient elastography is useful in prediction of significant portal hypertension ( PHT). To evaluate the usefulness of baseline and serial LSM in predicting clinical disease progression ( CDP) for patients with compensated hepatic cirrhosis. Methods Consecutive patients with compensated cirrhosis and without hepatocellular carcinoma ( HCC) were prospectively enrolled. Baseline LSM was assessed at enrolment, then at a 6- to 12-month interval. Esophagogastroduodenoscopy and ultrasonography were performed regularly for surveillance of varices and HCC, while CDP including HCC development and PHT progression was recorded. Results Two hundred and twenty patients were enrolled. In a median follow-up of 36.9 months, CDP were detected in 49 patients including 30 PHT progression and 19 HCC developments. The cumulative incidence of CDP, PHT progression and HCC development at 3 years was 20.7%, 12.8% and 9.1% respectively. Multivariate analyses showed that baseline LSM was an independent predictor of PHT progression and CDP, however, not of HCC occurrence. The performance of baseline LSM in predicting PHT progression, varices growth/development and hepatic decompensation was 0.744, 0.638 and 0.929. With 17, 12 and 21.1 kPa as the cut-off, the negative predictive value was 92, 94 and 99% respectively. Patients with baseline LSM ≧17 kPa without serial changes had higher risk of PHT progression. Conclusion For patients with compensated cirrhosis, LSM was an independent predictor of PHT progression and CDP, but not of HCC occurrence. Baseline LSM was useful to exclude PHT progression. Patients with baseline and serial LSM ≧17 kPa had higher risk of PHT progression. [ABSTRACT FROM AUTHOR]

The influential roles of antibiotic prophylaxis on cirrhotic patients with peptic ulcer bleeding are still not well documented. The purpose of this study is to clarify these influential roles and to identify the risk factors associated with rebleeding, bacterial infection and in-hospital mortality. A cross-sectional, chart review study was conducted on 210 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients were divided into group A (with prophylactic intravenous ceftriaxone, n = 74) and group B (without antibiotics, n = 136). The outcomes were length of hospital days, prevention of infection, rebleeding rate and in-hospital mortality. Our results showed that more patients suffered from rebleeding and infection in group B than group A (31.6% vs. 5.4%; p<0.001 and 25% vs. 10.8%; p = 0.014 respectively). The risk factors for rebleeding were active alcoholism, unit of blood transfusion, Rockall score, model for end-stage liver disease score and antibiotic prophylaxis. The risk factors for infection were active alcoholism, Child-Pugh C, Rockall score and antibiotic prophylaxis. Rockall score was the predictive factor for in-hospital mortality. In conclusions, antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and rebleeding rate but not in-hospital mortality. Rockall score was the predictive factor of in-hospital mortality. [ABSTRACT FROM AUTHOR]

Liver stiffness measurement (LSM) using transient elastography has been proposed to assess liver fibrosis well in various liver diseases. This study was to determine the changes of LSM and its associated factors for chronic hepatitis B (CHB) patients undergoing Entecavir therapy. Consecutive CHB patients underwent Entecavir therapy with two LSMs were enrolled. Patients with aspartate transaminase (AST) and/or alanine transaminase ≧200 IU/L were excluded. The retrospective study enrolled 233 patients including 132 without cirrhosis (group 1) and 101 with cirrhosis (group 2). The mean values of initial liver stiffness were 7.9 and 16.6 kPa for patients in group 1 and group 2, respectively (p<0.001). In addition to the decline of transaminase levels, there was significant reduction of liver stiffness value in a mean interval of 52.8 and 61.9 weeks between the two LSMs for patients in group 1 and 2, respectively (p<0.001). Multivariate analysis showed that higher initial LSM value and presence of hepatitis B e-antigen were associated with a greater decline of LSM value, whereas follow-up AST≧40 IU/L with increased LSM value for group 1 patients. For group 2 patients, longer interval between the two LSMs, higher initial LSM value and AST≧40 IU/L were associated with a greater decline of LSM value, whereas presence of diabetes mellitus (DM) contributed to increased LSM value. In conclusion, CHB patients improved their LSM values after Entecavir therapy. Higher initial LSM value contributed to greater LSM reduction. However, in cirrhotic patients, DM was associated with an increased LSM value after therapy. [ABSTRACT FROM AUTHOR]

: Antibiotic prophylaxis with norfloxacin, intravenous ciprofloxacin, or ceftriaxone has been recommended for cirrhotic patients with gastrointestinal hemorrhage but little is known about intravenous cefazolin. This study aimed to compare the outcome of intravenous cefazolin and ceftriaxone as prophylactic antibiotics among cirrhotic patients at different clinical stages, and to identify the associated risk factors. The medical records of 713 patients with acute variceal bleeding who had received endoscopic procedures from were reviewed. Three hundred and eleven patients were entered for age-matched adjustment after strict exclusion criteria. After the adjustment, a total of 102 patients were enrolled and sorted into 2 groups according to the severity of cirrhosis: group A (Child’s A patients, n = 51) and group B (Child’s B and C patients, n = 51). The outcomes were prevention of infection, time of rebleeding, and death. Our subgroup analysis results failed to show a significant difference in infection prevention between patients who received prophylactic cefazolin and those who received ceftriaxone among Child’s A patients (93.1% vs. 90.9%, p = 0.641); however, a trend of significance in favor of ceftriaxone prophylaxis (77.8% vs. 87.5%, p = 0.072) was seen among Child’s B and C patients. More rebleeding cases were observed in patients who received cefazolin than in those who received ceftriaxone among Child’s B and C patients (66.7% vs. 25.0%, p = 0.011) but not in Child’s A patients (32% vs. 40.9%, p = 0.376). The risk factors associated with rebleeding were history of bleeding and use of prophylactic cefazolin among Child’s B and C patients. In conclusion, this study suggests that prophylactic intravenous cefazolin may not be inferior to ceftriaxone in preventing infections and reducing rebleeding among Child’s A cirrhotic patients after endoscopic interventions for acute variceal bleeding. Prophylactic intravenous ceftriaxone yields better outcome among Child’s B and C patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Transient elastography (TE) has been useful in esophageal varices (EV) diagnosis for chronic hepatitis C patients. In the present study, we evaluate the usefulness of TE and simple blood markers in the EV diagnosis of patients with hepatitis B virus (HBV)-related cirrhosis, prospectively. Methods: Consecutive patients with compensated cirrhosis and positive HBV surface antigen were enrolled, prospectively. At enrollment, the aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR) and the AST to platelet ratio index (APRI) were recorded, and TE was performed. Two experienced endoscopists assessed EV independently. High-risk EV was defined as small size with a red color sign, and medium or large in size. The diagnostic performances, optimal cut-offs, and the validities of TE, APRI, platelet count (PLT), and AAR in EV diagnosis were assessed. Results: A total of 126 patients (male/female: 93/33; mean age: 54.5 years) with reliable TE results were analyzed. There was good agreement between two endoscopists in assessing the presence of EV and high-risk EV (kappa value: 0.82 and 0.96). Forty-eight (38.1%) patients had EV (small: 35; high risk: 13). There was correlation between TE result and EV size (r = 0.515, P < 0.001). TE, APRI, and PLT were similar; however, superior to AAR in the diagnostic accuracies for EV and high-risk EV. In high-risk EV prediction, the negative predictive value (NPV) was 97%, 98%, and 98%, with cut-offs of 21 kPa, 1.24, and 110 (× 109/L) for TE, APRI, and PLT, respectively. Conclusions: For compensated patients with HBV-related cirrhosis, TE, APRI, and PLT are useful in excluding high-risk EV with high NPV. [ABSTRACT FROM AUTHOR]

Background/Purpose: Chronic hepatitis C (CHC) shows a significant association with cirrhosis and hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is important in the diagnosis of HCC, but elevated AFP levels have also been observed in CHC without HCC. We evaluated the clinical correlation between elevated AFP levels and CHC. Methods: From April 1999 to November 2004, 654 CHC patients with no evidence of HCC from imaging studies were collected by chart review. Results: The prevalence of elevated AFP levels (≥ 15 ng/mL) was 23.9%. Univariate analysis revealed that age, histological activity index (HAI) fibrosis score of 3/4, HAI inflammation score ≥ 7, aspartate amino-transferase (AST) and alanine transaminase (ALT) levels, AST/ALT ratio, and total bilirubin level were associated with elevated AFP levels. Multivariate analysis revealed that age (≥ 55 vs. < 55 years), HAI inflammation score (≥ 7 vs.. < 7), ALT (> 150 vs.. ≤ 150 U/L), and platelet count (≤ 150 × 109 vs. > 150 × 109 cells/L) were associated with elevated AFP levels. Multivariate analysis also revealed that hepatitis C virus (HCV) genotype 1b, platelet count ≤ 150 × 109 cells/L, AST > 80 U/L and AFP ≥ 6 ng/mL were associated with advanced fibrosis. Using a cut-off AFP level of ≥ 6.0 ng/mL, the sensitivity and specificity of diagnosing fibrosis score 3/4 was 74.3% and 68.4%, respectively. Using a cut-off AFP level of ≥ 15.0 ng/mL, the sensitivity and specificity of diagnosing fibrosis score 3/4 was 35.7% and 91.1%, respectively. Conclusion: Elevated AFP levels were observed in 23.9% of patients with CHC. Elevated AFP levels correlated positively with age, HAI inflammation score, ALT elevation, and thrombocytopenia. In addition, HCV genotype 1b, thrombocytopenia, AST elevation, and AFP level ≥ 6 ng/mL were associated with advanced fibrosis. [Copyright &y& Elsevier]