Acute on Chronic Liver Failure: Role of the Bacterial Infections

Acute-on-chronic liver failure (ACLF) refers to a syndrome characterized by acute deterioration of liver function of a pre-existing chronic liver disease with increased short-term mortality at 3 months due to multiorgan failure. Definition of ACLF has been refined, but differences between western and eastern areas still exist. Diagnosis of ACLF as recommended by the EASL-CLIF consortium is based on the assessment of organ dysfunction. The pathogenesis of this syndrome is attributable to an exaggerated host response to inflammation, responsible for the severe haemodynamic derangement leading to multiorgan failure. ACLF is triggered by precipitating events like acute hepatitis either viral, drug-induced, toxic, or alcoholic, variceal bleeding and sepsis. Bacterial infection is currently considered the most frequent trigger of ACLF in Western countries. Cirrhotic patients, particularly if decompensated are prone to develop bacterial infection because loss of integrity of the intestinal mucosal barrier and translocation of pathogen-associated molecular patterns (PAMPs). Bacterial translocation may develop into overt infection at different sites, along with sepsis and septic shock that may lead to ACLF. Epidemiology of bacterial infection in cirrhosis has been changing and this accounts for new antibiotic regimens as empirical therapy in critically ill cirrhotic patients with bacterial infection. In this chapter, we will discuss on definition, pathogenesis, clinical aspects and therapy of bacterial infection-related ACLF

Periarticular injection and continuous femoral nerve block versus continuous femoral nerve block alone on postoperative opioid consumption and pain control following total knee arthroplasty: Randomized controlled trial

© 2017 Continuous femoral nerve block (CFNB) has been used to prevent the breakthrough pain after total knee arthroplasty (TKA). Multimodal drug injection (PMDI) has also been shown to decrease opioid consumption and pain. We investigated whether the use of PMDI further improves analgesic and rehabilitation outcomes when used in conjunction with CFNB. This is a prospective randomized controlled study of 44 patients undergoing primary TKA. The treatment group (n = 23) received a PMDI of combined ropivacaine, epinephrine, ketorolac and morphine, and the controlled group (n = 21) received saline at wound closure. Total opioid consumption, pain scores, knee range of motion (ROM) outcomes, length of stay, and patient satisfaction were measured and compared. The total consumption of morphine is similar between the two groups (52.6 ± 40.6 vs. 41.5 ± 32.9, p = 0.325). The mean morphine consumption of the treatment group was significantly lower than the control at 4 h after surgery (4.2 ± 5.5 vs. 11.3 ± 8.1, p = 0.002) but comparable on POD1, POD2, and POD3. The mean pain scores were significantly higher in the treatment group than the control group at POD2 (at rest: 47.3 ± 29.1 vs. 23.8 ± 20.6, p = 0.004; after PT: 57.7 ± 25.4 vs. 35.2 ± 26.8, p = 0.007) and POD3 (at rest: 30.9 ± 30.3 vs. 14.8 ± 20.9, p = 0.045; after PT: 50.2 ± 30.6 vs. 29.0 ± 32.1, p = 0.035), and not significantly different at 4 h after surgery or at POD1. Mean maximal knee flexion ROM in degrees during active and active assisted mobilization showed no significant difference between the control and the treatment groups on POD2 and POD3. The mean length of stay of the treatment group is significantly longer than the control group (5.1 ± 2.1 vs. 3.8 ± 1.6, p = 0.032). At discharge, no significant difference exists between the two groups for mean patient satisfaction. The addition of PMDI led to a decrease in opioid consumption in the immediate postoperative period but with no significant difference in the total consumption within the first three days postoperatively. This finding provides an opportunity for appropriate preoperative treatment and education for both patients and caregivers

Triple antiviral therapy in HCV positive patients who failed prior combination therapy

AIM: To assess the efficacy of triple therapy (peginte-rferon or high dose standard interferon, plus ribavirin and amantadine) in nonresponders to prior combination therapy. METHODS: A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 mug/wk of peginterferon-alpha-2a (40 kDa) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group A) or interferon-alpha-2a (6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group B). RESULTS: Overall sustained virologic response (SVR) was 26.6% (32.1% and 19.5% in group A and B, P = 0.057). Baseline ALT > 120 UI/L (OR 2.4; 95% CI: 1.11 to 5.20; P = 0.026) and HCV RNA negativity after 12 wk (OR 8.7; 95% CI: 3.87 to 19.74; P < 0.0001) were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon (P = 0.036). CONCLUSION: More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity

OBJECTIVES: We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. METHODS: We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. RESULTS: 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). CONCLUSIONS: Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 64 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score &gt; 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p &lt; 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p &lt; 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations

The Effect of Tuberculosis on the Mortality of Cirrhotic Patients: A Population-Based 3-Year Follow-Up Study

[[abstract]]Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. It is still unknown if TB, like other infectious diseases contributes a poor prognosis in cirrhotic patients. The aim of this study was to investigate the impact of TB on the mortality of cirrhotic patients. National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 434 cirrhotic patients with new diagnosis of TB between January 1, 2007 and December 31, 2007. The comparison group consisted of 4340 selected cirrhotic patients without TB in the same period by propensity score matching analysis. The 30-day, 90-day, 1-year and 3-year mortalities were 10.1%, 24.2%, 43.1%, and 63% in the TB group, and 7.9%, 15.5%, 31.2%, and 53.4% in the non-TB group. After Cox proportional hazard regression model adjusted by the patients' gender, age, and comorbid disorders, the hazard ratios (HR) in cirrhotic patients with TB for 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 1.33 [95% confidence interval (CI) 0.97-1.83], 1.91 (95% CI 1.45-2.51), 1.46 (95% CI 1.16-1.84), and 1.10 (95% CI 0.88-1.37), compared to the non-TB group. In conclusion, TB is a risk factor for the mortality of cirrhotic patients. The effect focused on the 30-day to 1-year after diagnosis of TB.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]紙本[[countrycodes]]IN

A Liver Index and its Relationship to Indices of HCC Aggressiveness

A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Development and validation of a new prognostic system for patients with hepatocellular carcinoma.

Background Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. Methods and Findings Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI. CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child\u2013 Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26\u2013106 mo) and 39 mo for Taiwanese patients (interquartile range, 12\u201361 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2\u20133), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4\u20135), and 9 and 8 mo in quartile 4 (ITA.LI.CA score &gt; 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p &lt; 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score\u2019s prognostic ability was significantly better (p &lt; 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. Conclusions The ITA.LI.CA prognostic system includes both a tumor staging\u2014stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)\u2014and a prognostic score\u2014integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations