Higher Child-Pugh Score Research Articles

Impact of Sustained Viral Response in the Evolution of Minimal Hepatic Encephalopathy: a Prospective Pilot Study

Introduction and aimsTo determine the prevalence of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. Material and methodsWe performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. Results64 patients were included. 51.6% were male, the median age was 62years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 KPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). ConclusionWe found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Cephalosporin resistance in community acquired spontaneous bacterial peritonitis.

Objective:To determine 3rd generation cephalosporin resistance in patients with community-acquired spontaneous bacterial peritonitis (SBP) using early response assessment.Methods:This prospective quasi-experimental study was carried out at Doctors Hospital & Medical Center from January 2016 to September 2018. Patients with cirrhosis and SBP were included. Third generation cephalosporins i.e. cefotaxime/ceftriaxone were used for treatment of SBP. Response after 48 hours was assessed and decline in ascitic fluid neutrophil count of < 25% of baseline was labelled as cephalosporin resistant. Carbapenem were used as second line treatment. Recovery and discharge or death of patients were primary end points.Results:Male to female ratio in 31 patients of SBP was 1.2/1 (17/14). Hepato-renal syndrome was diagnosed in 11(37.9%) patients. Cefotaxime was used for 16(51.6%) patients whereas ceftriaxone for 15(48.3%) patients. Early response of SBP was noted in 26(83.8%) patients while 5 (16.2%) were non-responders to cephalosporins. SBP resolved in all non-responding patients with i/v carbapenem. In-hospital mortality was 12.9% and had no association with cephalosporin resistance. High bilirubin (p 0.04), deranged INR (p 0.008), low albumin (p 0.04), high Child Pugh (CTP) score (p 0.03) and MELD scores (p 0.009) were associated with in-hospital mortality.Conclusion:Cephalosporin resistance was present in 16.2% of study patients with community-acquired SBP. Mortality in SBP patients is associated with advanced stage of liver disease.

Analysis of survival and prognostic factors in treatment of hepatocellular carcinoma in Spanish patients with drug-eluting bead transarterial chemoembolization.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) improves the survival of patients with hepatocellular carcinoma (HCC), intermediate stage [i.e. Barcelona Clinic Liver Cancer-B (BCLC-B)]. The aim of our study was to analyse the overall survival (OS) and prognostic factors of patients with HCC treated with DEB-TACE. Patients' clinical course was recorded from January 2005 to July 2014. The median OS was obtained by the Kaplan-Meier method and compared using the log-rank test. The prognosis factors associated with OS were determined by a multivariate Cox regression analysis and the accuracy of the OS prediction was determined by calculation of the assessment for retreatment with TACE score (ART score). A cohort of 147 consecutive patients treated with DEB-TACE was included. Median age of the patients was 73.4 years. Overall, 68.7% were men, and all had cirrhosis, with 68.8% being hepatisis C virus positive. Moreover, 35.2% were staged as BCLC-A and 60.2% as BCLC-B. After a median follow-up of 19.2 months, 29.3% were alive, 4.3% needed treatment with sorafenib and 56.1% underwent DEB-TACE retreatment. Median OS was 22.8 [95% confidence interval (CI)=19.6-25.9]. After censoring for ascites and more than one nodule, OS was 23.87 (95% CI =20.72-27.01) and 26.89 (95% CI =21.00-32.78), respectively. The risk of death decreased by 22.3% with the number of DEB-TACE sessions (hazard ratio=0.777) and increased by 25.9% with higher Child-Pugh score (hazard ratio=1.259). Overall, 61.2% of the cohort had an ART score between 0 and 1.5. There were no statistical differences in OS between cohort groups with ART of 0-1.5 and at least 2.5. The results validate the efficacy and safety of DEB-TACE in patients with HCC and the importance of some prognostic factors for patient survival.

Endoscopic treatment or balloon-occluded retrograde transvenous obliteration is safe for patients with esophageal/gastric varices in Child-Pugh class C end-stage liver cirrhosis.

Background/AimsThere is a controversy about the availability of invasive treatment for esophageal/gastric varices in patients with Child-Pugh class C (CP-C) end-stage liver cirrhosis (LC). We have evaluated the validity of invasive treatment with CP-C end-stage LC patients.MethodsThe study enrolled 51 patients with CP-C end-stage LC who had undergone invasive treatment. The treatment modalities included endoscopic variceal ligation in 22 patients, endoscopic injection sclerotherapy in 17 patients, and balloon-occluded retrograde transvenous obliteration (BRTO) in 12 patients. We have investigated the overall survival (OS) rates and risk factors that contributed to death within one year after treatment.ResultsThe OS rate in all patients at one, three, and five years was 72.6%, 30.2%, and 15.1%, respectively. The OS rate in patients who received endoscopic treatment and the BRTO group at one, three, and five years was 67.6%, 28.2% and 14.1% and 90.0%, 36.0% and 18.0%, respectively. The average of Child-Pugh scores (CPS) from before treatment to one month after variceal treatment significantly improved from 10.53 to 10.02 (P=0.003). Three significant factors that contributed to death within one year after treatment included the presence of bleeding varices, high CPS (≥11), and high serum total bilirubin levels (≥4.0 mg/dL).ConclusionsThe study demonstrated that patients with a CPS of up to 10 and less than 4.0 mg/dL of serum total bilirubin levels may not have a negative impact on prognosis after invasive treatment for esophageal/gastric varices despite their CP-C end-stage LC.

Lymphocyte-to-Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma.

Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment.

Impact of Sustained Viral Response in the Evolution of Minimal Hepatic Encephalopathy: a Prospective Pilot Study

Introduction and aims. To determine the prevalence of minimal hepatic encephalopathy (MHE) in patients with liver cirrosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. Material and methods. We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. Results. 64 patients were included. 51.6% were male, the median age was 62years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 KPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p &lt; 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p &lt; 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). Conclusion. We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

PS01.039: RECURRENCE PREDICTION EQUATION OF ESOPHAGEAL VARICES

Abstract Background Endoscopic treatment is widely performed for esophageal varices, but prediction of post-treatment recurrence is difficult. Methods The subjects were 298 patients with cirrhosis who underwent initial endoscopic treatment for esophageal varices from January 1997 to December 2010 and were followed-up at our hospital. The average age was 64.5 years (29–84) and the male/female ratio was 119:89. The causes of cirrhosis were hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholism, non-alcoholic steatohepatitis (NASH), and others in 66, 14, 13, 3 and 4% of the subjects, respectively. Hepatic reserve capacity before treatment was Child-Pugh score 6.9 ± 1.5 points, albumin 3.2 ± 0.6 g/dl, total bilirubin 1.4 ± 0.7 mg/dl, and PT% 71.0 ± 13.8%. Complication of hepatocellular cancer (HCC) was present in 63 subjects (30.4%). Treatment-indicated recurrence was defined as ³F2 and ³RC2. Recurrence occurred in 102 subjects, including 65 who redeveloped varicosity within 1 year. Data were compared between patients with (n = 65) and without (n = 43) early recurrence (within 1 year). Results The early recurrence group had a significantly higher Child-Pugh score (7.4 ± 1.8 vs. 6.7 ± 1.3, P &lt; 0.01), total bilirubin (1.6 ± 0.8 vs. 1.2 ± 0.6 mg/dl, P &lt; 0.01), and HCC complication rate (44.6% vs. 23.9%, P &lt; 0.01), and significantly lower albumin (3.0 ± 0.7 vs. 3.3 ± 0.6 g/dl, P &lt; 0.01) and administration rate of antihypertensive drugs (10.8% vs. 41.0%, P &lt; 0.01). In multivariate logistic regression analysis, use of antihypertensive drugs, total bilirubin, HCC, underlying disease (alcoholism), and treatment method (endoscopic injection sclerotherapy [EIS] or endoscopic variceal ligation [EVL]) emerged as factors that affected early recurrence. Based on these findings, we developed the following predictive equation: recurrence time (months) = - 12.5206 (HCC: confirmed = 1, not confirmed = 0) - 3.5029 (total bilirubin) + 6.2169 (antihypertensive drug: used = 1, not used = 0) - 7.2581 (alcoholism: yes = 1, no = 0) - 6.0764 (EVL = 1, EIS = 0) + 35.7165. Based on this formula, we examined the predicted and actual recurrence times in 68 subjects from January 2011 to December 2012 and found a significant positive correlation between these data (R = 0.583, P &lt; 0.01). Conclusion An equation was developed for prediction of recurrence of esophageal varices after treatment and was shown to have utility in actual cases. Disclosure All authors have declared no conflicts of interest.

Clinical impact of healthcare-associated acquisition in cirrhotic patients with community-onset spontaneous bacterial peritonitis.

Background/AimsHealthcare-associated (HCA) infection is a recently suggested new category of community-onset infections. The implications of HCA infections in terms of diagnosis, treatment, and outcomes of spontaneous bacterial peritonitis (SBP) are not well understood. We sought to delineate the differences between community-acquired (CA) SBP and HCA SBP with specific interest in the antimicrobial resistance of causative microorganisms and outcomes.MethodsWe conducted a retrospective cohort study of all SBP episodes with positive ascitic culture and/or blood culture from June 2000 to August 2011. Community-onset SBP episodes were included when they occurred within 48 hours after admission and were classified as CA SBP and HCA SBP based on the predefined criteria.ResultsA total of 188 episodes of community-onset SBP were analyzed (65.4% HCA SBP and 34.6% CA SBP). HCA SBP had a higher resistance rate to third-generation cephalosporin (6.8% vs. 1.6%, p = 0.168). The overall 30-day mortality was similar between both groups (37.4% vs. 41.5%, p = 0.638). The independent risk factors for 30-day all-cause mortality in community-onset SBP included high Child-Pugh score, acute kidney injury, and resistance to third-generation cephalosporins; HCA infection was not associated.ConclusionsHepatic functional status, renal dysfunction, and third-generation cephalosporin resistant pathogens more adversely affected the outcome of cirrhotic patients with community-onset SBP rather than HCA infection. The higher rate of third-generation cephalosporin resistance was notable in HCA SBP, which will require a novel approach to empirical antibiotic treatment selection in this population.

Abstract No. 532 Percutaneous portal vein stent placement: efficacy and predictors of patency: a single-center experience in 27 patients

To evaluate patency of portal vein (PV) stents and identify factors and predictors of stent patency. From May 2007 to March 2017, 27 patients (17 males, 10 females, mean age of 60.3, range 37-83) with main PV stenosis successfully treated with percutaneous stent were reviewed. Etiologies included: cholangiocarcinoma (n = 16), OLT stricture (n = 4), HCC (n = 3), gastric cancer (n = 2), colon cancer (n = 1) and surgical injury (n = 1). Overall survival (OS), primary patency (PP, assessed with abdominal Doppler, CT or MRI) and lab values were recorded. Mean OS was 538.5 days compared to mean PP of 533.3 days (range, for both 18-3758). Splanchnic vein involvement (p = 0.003), Child-Pugh score (p = 0.047), PV occlusions (p = 0.018), age at procedure (p = 0.038), and primary tumor staging (p = 0.045) were all found to be correlates associated with decreased PV stent patency. Specifically, patients with a primary tumor staging greater than 2 experienced decreased PV stent patency (p = 0.0183). Patients with an albumin level greater than 3 g/dL (p = 0.0017), or an alkaline phosphatase level within the normal range of 44-147 U/L (p = 0.0008) at the time of procedure experienced statistically significant longer patency. PV stent placement is safe with moderate primary patency. Factors associated with decreased patency include splanchnic vein involvement, high Child-Pugh score, PV complete occlusion, and primary tumor component (T) of TNM cancer staging. Albumin and alkaline phosphatase levels at time of procedure are predictive for portal vein stent patency.

Covert hepatic encephalopathy leads to distinct alterations in the emotional state, independently of MELD-Score.

Covert hepatic encephalopathy impairs many aspects of quality of life, although its impact on the emotional state has not been evaluated. This study aims to evaluate the impact of covert hepatic encephalopathy on the emotional state and which factors are associated with changes in the emotional state in patients with cirrhosis. This single-center study included all patients with cirrhosis who underwent the portosystemic encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional state assessment with the Eigenschaftswörterliste 60-S in 2011. Covert hepatic encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests were used according to variable distribution. One hundred seventeen patients with cirrhosis were included (median age: 59 [interquartile range: 48 - 67], 32 %female, 74 % alcohol-associated). Seventy patients had covert hepatic encephalopathy (60 %) with a higher MELD (16[interquartile range: 13 - 21], p = 0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without encephalopathy. Patients with covert encephalopathy felt reduced mental activity (p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p = 0.021). The scores in the negative domains such as general lethargy (p = 0.031) and anxiousness/depressiveness (p = 0.033) were higher in patients with covert hepatic encephalopathy. There was no correlation between MELD and the emotional state. Patients with 2 pathological tests (critical flicker frequency and PSE) showed the most distinct alterations in the emotional state in the group of patients with covert hepatic encephalopathy. Patients with covert hepatic encephalopathy have an alteration of the emotional state, which is more marked in patients with 2 pathological tests. Interestingly, MELD had no impact on the emotional state.

Muscle fat infiltration assessed by total psoas density on computed tomography predicts mortality in cirrhosis.

Background:Ongoing evidence suggests that sarcopenia adversely affects outcomes in cirrhosis. The aim of this study was to evaluate muscle fat infiltration as a component of sarcopenia and its prognostic value in this setting.Methods:In 98 consecutive patients with cirrhosis, muscle density was measured during a computed tomography scan at the level of the fourth to fifth lumbar (L4) vertebrae. Univariate and multivariate Cox regression analysis was used to determine predictors of survival.Results:Body mass index: median 26 (range 17-45.2); model for end-stage liver disease (MELD) score: median 11 (6-29); Child-Pugh (CP) score: median 7 (5-13), CP class: A=49 (50.5%), B=39 (40%), C=10 (9.5%); hepatocellular carcinoma: 14 (14.3%); follow up: median 45 (1-140) months. Median L4 total psoas area (TPA): 2022 (777-3806) mm2; L4 average total psoas density (ATPD): 42.52 (21.26-59.8) HU. ATPD was significantly correlated with age (r=-0.222, P=0.034), creatinine (r=-0.41, P<0.001), albumin (r=0.224, P=0.035), MELD score (r=-0.218, P=0.034), and TPA (r=0.415, P<0.001). Fifty-four patients (55.1%) died during follow up. In the multivariate analysis, higher CP score (hazard ratio [HR] 1.2, 95% confidence interval [CI] 1.04-1.41), advanced age (HR 1.038, 95%CI 1.006-1.07) and lower ATPD (HR 0.967, 95%CI 0.937-0.997) were predictors of mortality.Conclusion:Muscle fat infiltration, as a result of sarcopenia, is a negative predictive factor of survival in cirrhosis, emphasizing the need for early identification of this subgroup of patients.

Bacterial Infection and Predictors of Mortality in Patients with Autoimmune Liver Disease-Associated Acute-On-Chronic Liver Failure.

Objective To date, few studies are available on autoimmune liver disease-associated acute-on-chronic liver failure (ACLF). The aim of this study is to investigate bacterial infection and predictors of mortality in these patients. Methods We retrospectively studied patients with autoimmune liver disease from August 2012 to August 2017. Clinical data of the patients were retrieved for analysis. Results There were 53 ACLF patients and 53 patients without ACLF in this study. The ACLF group had a higher prevalence of complications (P < 0.05). The 28-day and 90-day mortality rates were also obviously high in patients with ACLF (38.3% and 74.5%, resp.) (P < 0.05). No predictor was significantly associated with 28-day and 90-day transplant-free mortality. In 53ACLF patients, 40 (75.5%) patients showed bacterial infection. ACLF patients with bacterial infection showed high Child-Pugh score, MELD score, CLIF-SOFA score, 28-day mortality, and 90-day mortality (P > 0.05). Moreover, C-reactive protein (CRP) using 12.15 mg/L cut-off value proved to be more accurate than procalcitonin in identifying patients with infection. Conclusions Autoimmune liver disease-associated ACLF showed more complications and high mortality. Bacterial infection patients displayed a more severe condition than those without infection. Elevated CRP is an accurate marker for diagnosing bacterial infection in autoimmune liver disease-associated ACLF patients.

Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients.

Chronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to severe liver failure, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Previous evidence has indicated that the dysbiosis of gut microbiota occurs after liver virus infection and is associated with severe liver disease. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in early-stage CHB and to understand their influence on disease progression. We investigated the gut microbial composition of stool samples from 85 CHB patients with low Child-Pugh scores and 22 healthy controls using the Illumina MiSeq sequencing platform. Furthermore, the serum metabolome of 40 subjects was measured by gas chromatography mass spectrometry. Compared with the controls, significant alteration in the gut microbiota was observed in the CHB patients; 5 operational taxonomic units (OTUs) belonging to Actinomyces, Clostridium sensu stricto, unclassified Lachnospiraceae and Megamonas were increased, and 27 belonging to Alistipes, Asaccharobacter, Bacteroides, Butyricimonas, Clostridium IV, Escherichia/Shigella, Parabacteroides, Ruminococcus, unclassified Bacteria, unclassified Clostridiales, Unclassified Coriobacteriaceae, unclassified Enterobacteriaceae, unclassified Lachnospiraceae and unclassified Ruminococcaceae were decreased. The inferred metagenomic information of gut microbiota in CHB showed 21 enriched and 17 depleted KEGG level-2 pathways. Four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224 (Streptococcus), and OTU55 (Haemophilus), had high correlations with hosts' hepatic function indices and 10 serum metabolites, including phenylalanine and tyrosine, which are aromatic amino acids that play pathogenic roles in liver disease. In particular, these 4 OTUs were significantly higher in patients with higher Child-Pugh scores, who also showed diminished phenylalanine and tryptophan metabolisms in the inferred gut metagenomic functions. These compositional and functional changes in the gut microbiota in early-stage CHB patients suggest the potential contributions of gut microbiota to the progression of CHB, and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.

Detection of bacterial DNA by in situ hybridization in patients with decompensated liver cirrhosis

BackgroundSpontaneous bacterial peritonitis (SBP) is often difficult to diagnose because bacteria in ascites cannot be detected accurately by conventional culture. In situ hybridization (ISH) was previously developed for rapid detection of genes from bacteria phagocytized by neutrophils. SBP may develop after bacteria enter into the systemic circulation following bacterial translocation. Therefore, we performed ISH to identify bacteria in blood samples collected from patients with decompensated liver cirrhosis (LC).MethodsIn this retrospective study, peripheral blood samples were collected from 60 patients with decompensated LC, and bacteria were detected by both blood culture and ISH. Moreover, 35 patients underwent paracentesis for diagnosis of SBP.ResultsEight of 35 patients were diagnosed with SBP by polymorphonuclear neutrophil counts, and one patient was diagnosed with bacterascites. Seven of the nine patients showed positive results for ISH, whereas bacteria were detected in only two cases by blood culture. Thirty-seven of 60 cases (62%) showed positive results for ISH, whereas only six samples (10%) were positive by blood culture analysis. Compared with the 23 cases of negative ISH, the 37 cases of positive ISH showed a higher frequency of fever, higher Child-Pugh scores, and lower albumin levels.ConclusionsDetection of bacteria by ISH suggested that bacterial translocation, which cannot be proven by conventional culture, occurred in these patients, and that ISH could be helpful for the early diagnosis of some types of infection and prevention of SBP in these patients.

Transjugular intrahepatic portosystemic shunt treatment of variceal bleeding in an unselected patient population

Objective: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) in variceal bleeding in a clinical setting.Materials and methods: Retrospective review of 131 patients (116 with liver cirrhosis) treated with TIPS with covered stent grafts in a single centre from 2002 to 2016.Results: Survival at 1 and 2 years was 70% and 57% in patents with, and 100% at 2 years in patients without liver cirrhosis, respectively. A high Child–Pugh score and severe hepatic encephalopathy (HE) within 12 months post-TIPS were related to increased mortality. Re-bleeding occurred in 8% within 12 months and was related to TIPS dysfunction and a post-TIPS portosystemic gradient (PSG) of ≥5 mmHg. The main cause of TIPS dysfunction was that the stent did not fully reach the inferior vena cava. There was no correlation between the PSG and the occurrence of HE.Conclusions: TIPS was safe and prevented re-bleeding in patients with variceal bleeding, with or without liver cirrhosis, regardless of Child–Pugh class and of how soon after bleeding onset, the TIPS procedure was performed. A post-TIPS PSG of ≥5 mmHg was associated with an increased risk for re-bleeding and there was no correlation between the post-TIPS PSG and the occurrence of HE.

Clinical Impact of Intrapulmonary Vascular Dilatation in Candidates for Liver Transplant

Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease. We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 Study, a multicenter, prospective cohort study of patients being evaluated for liver transplant. We excluded patients with obstructive or restrictive lung disease, HPS, or intracardiac shunting. We compared patients with and those without IPVD. Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6[interquartile range (IQR), 5-7] vs5 [IQR, 4-7]; P= .04), possibly higher Model for End-Stage Liver Disease scores (14.5 [IQR, 11.6-15.8] vs12.2 [IQR, 9.4-15.5]; P= .06), higher PaO2 levels (97.9 [IQR, 92.0-103.0] vs89.0 [IQR, 82.0-96.9] mmHg; P< .001), and lower A-a gradients (9.9 [IQR, 6.2-13.5] vs14.9 [IQR, 9.0-21.8] mmHg; P< .001). Symptoms and quality of life were similar between the groups. Autoimmune hepatitis and increased liver disease severity were associated with the presence of IPVD, which was characterized by higher PaO2 levels. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

Prevalence and Impact of Bacterial Infections in Children With Liver Disease—A Prospective Study

Risk of infections is increased in patients with Acute Liver Failure (ALF) and Decompensated Chronic Liver Disease (DCLD). We evaluated the frequency, site, type and risk-factors for bacterial infections in children with ALF and DCLD and its effect on outcome. ALF or DCLD children were enrolled prospectively. Clinical and laboratory details were recorded. Cultures (blood, urine and ascites) and chest X-ray were done at admission followed by weekly surveillance cultures. 173 patients, 68 ALF and 105 DCLD were enrolled. Infections were more common in DCLD than ALF (60/105 [57.1%] vs. 27/68 [39.7%]; P=0.02). Ascitic fluid infection, pneumonia, urinary tract infection and bacteremia were seen in 19%, 17.9%, 13.2% and 12.1% patients respectively. Healthcare-Associated (HCA) infections were most frequent (39/87, 44.8%), followed by Nosocomial (NC, 32%) and Community-Acquired (CA, 23%). Nearly 3/4th of bacterial isolates were resistant to cephalosporins and quinolones, 23% being Multiresistant Bacteria (MRB). DCLD patients with infection had higher Child-Pugh Score (10 [6-14] vs. 7 [6-14]; OR 3.2 [1.77-5.10]: P=0.007), need for ICU care (26/60 vs. 3/45; OR 10.70 [2.98-38.42]: P=0.01), in-hospital mortality (24/60 vs. 8/45;OR 3.08 [1.22-7.75]: P=0.04) and mortality at 3 month follow-up (32/60 vs. 9/45; OR 4.57 [1.87-11.12]: P=0.00). Infection did not affect the outcome in ALF. Infections develop in 40% ALF and 57% DCLD children. HCA and NC infections account for 77% of infections. Most culture isolates are resistant to cephalosporins and fluoroquinolones and 23% have MRB. Risk of infections is higher in DCLD patients with advanced liver disease.

Bacterial meningitis complicating the course of liver cirrhosis.

Patients with cirrhosis and bacterial meningitis were enrolled. Cirrhosis was defined by liver histology or clinical, laboratory, and ultrasonographic and endoscopic findings. Bacterial meningitis was defined by cerebro-spinal fluid pleocytosis (>10/mcl) and characteristic clinical presentation. Fisher exact test and Wilcoxon rank-sum test were employed as appropriate for statistical analysis. Forty-four patients with bacterial meningitis and cirrhosis were enrolled in the study. Sex ratio (male:female) was 1.4:1 and median (IQR) age was 64 (55-72) years. Cirrhosis was viral in 40 patients. At admission, median (IQR) MELD score was 12 (9-14), and median (IQR) Child-Pugh score was 8 (6-10). Other conditions associated with immunodepression were present in 22 (50%) cases. Streptococcus pneumoniae and Listeria monocytogenes were the agents more frequently identified. An extra-meningeal focus of infection was identified in 17 (39%) cases. Main symptoms at admission were fever, nuchal rigidity, and an obtunded or comatose status, and at least 2 of these were reported in 37 (84%) episodes. Cerebro-spinal fluid showed high cells, low CSF/serum glucose ratio, and elevated protein. Seventeen patients (39%) died and 8 (18%) reported sequelae. High MELD and Child-Pugh scores were related to the mortality risk (p<0.001). The findings of blood and cerebro-spinal fluid analysis were not predictive of outcome. Bacterial meningitis should be considered in cirrhotics presenting with fever and altered conscience status. MELD and Child-Pugh scores predicted prognosis.

Erythropoietin and hepatocellular carcinoma: What is patients survival outcome?

e15660 Background: Erythropoietin (Epo) is a glycoprotein that stimulates cell proliferation and angiogenesis. Both, hypoxia and anemia are triggering factors that induce Epo overproduction. Although, previous studies reported that Epo induces angiogenesis in hepatocellular cancer (HCC), the relationship between Epo and HCC remains unclear .Our study aims to assess Epo level in HCC patients and evaluate its prognostic roles. Methods: We enrolled 766 HCC patients from MD Anderson Cancer Center Between 2001 and 2014. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. Based on the plasma level of Epo, we classified our patients into two groups: group 1 (N = 407) had normal serum level ( &lt; 20mIU/ml) and group 2 (N = 359) had higher level (≥20mIU/ml). Median overall survival (OS) was estimated by kaplan meier curve and log rank test. We used multivariate hazard ratio (HR) and 95% Confidence interval (CI) to determine the independent effect of Epo on the prognosis of HCC patients. Results: Univariate analysis showed that higher level of Epo had a statistically significant association to a higher Child Pugh Score (CTP), and an advanced stage in Barcelona clinic liver cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Median OS and 95%CI was 16.1 months (12.7 – 19.4) in group 1 compared to 11.4 months (8.6 – 14.3) in group 2 ( P&lt; .0001). The same significant difference was achieved among HCC patients with cirrhosis ( P = .005) and without cirrhosis ( P= .002). The estimated multivariate HR and 95%CI for elevated Epo level was 1.4 (1.04 – 1.9) (P = .03) in the absence of cirrhosis, while it was 0.97 (0.79 – 1.2) (P = .8) in the presence of cirrhosis after adjustment for several confounding factors. Conclusions: Abnormal Epo level in the plasma is significantly associated with a worse clinico-pathological characteristics and a shorter OS. Previous studies showed that HCC stimulates erythrocytosis and increases Epo production. Although, our study concluded that Epo is an independent prognostic factor among non-cirrhotic HCC patients only. Future studies are warranted to understand the mechanistic pathways of Epo effect in HCC patients and its variation in the presence and absence of cirrhosis.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.

BackgroundIncreasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown.MethodsWe prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively.ResultsThree hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients.ConclusionsThe microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.