Clinical classification of liver cirrhosis - a way to plan individual definitive treatment.

OBJECTIVE: Aim: To develop clinical classification of liver cirrhosis, which can aid individualization and planning definitive treatment for this group of patients. PATIENTS AND METHODS: Materials and Methods: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "liver", "cirrhosis" and "classification"; or "liver", "cirrhosis" and "complications"; or "liver", "cirrhosis" and "treatment"; or "portal" ", "hypertension" and "complications". Articles were independently evaluated by each author, the etiological, morphological and current clinical classifications of LC were analyzed, their advantages and disadvantages identified, and after discussion classification of LC was developed by consensus. CONCLUSION: Conclusions: The developed clinical classification of liver cirrhosis will facilitate the planning of therapeutic tactics for each patient, allow to personalize the treatment of patients with this pathology.

Preventing Readmissions of Hepatic Encephalopathy: Strategies in the Acute Inpatient, Immediate Postdischarge, and Longitudinal Outpatient Setting.

Hepatic encephalopathy (HE) is a strong predictor of early hospital readmission in patients with cirrhosis. Early hospital readmission increases health care costs and is associated with worse survival. Herein we provide an overview of strategies to prevent hospital readmissions in patients with HE, divided into 3 contexts: (a) acute inpatient, (b) immediate postdischarge, and (c) longitudinal outpatient setting.

Assessing the Predictive Efficacy of Lok Score in Identifying Esophageal Varices in Liver Cirrhosis Patients: A Cross-Sectional Study.

Introduction Liver cirrhosis is a global health concern with various etiologies, leading to portal hypertension and gastroesophageal varices. Variceal bleeding, a severe complication of cirrhosis, necessitates early detection and intervention to reduce mortality. Endoscopic screening is the gold standard for varices detection but is invasive and expensive. This study evaluates the Lok Score, a non-invasive predictive tool, for identifying esophageal varices in patients with liver cirrhosis. Materials and methods A cross-sectional study involving 150 liver cirrhosis patients was conducted. The Lok score was calculated using specific parameters. Patient data, including age, gender, etiology of liver cirrhosis, Child-Pugh class, varices presence, and grades, were recorded. Statistical analysis was performed using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp., and diagnostic parameters for Lok Score were computed. Results The study demonstrates that the Lok score exhibits significant potential as a predictive tool for esophageal varices. The mean Lok score significantly differed between individuals with and without varices, suggesting a correlation between Lok score and varices presence. Higher Lok scores may indicate more advanced varices. Utilizing the Lok score in clinical practice could lead to timely interventions, improving patient outcomes. Conclusion The Lok score shows promise as a valuable predictive tool for esophageal varices in liver cirrhosis patients. Early identification using this non-invasive parameter can aid in risk stratification and guide appropriate management strategies. However, further validation and larger studies are needed to fully integrate the Lok score into clinical practice for the benefit of cirrhosis patients.

Non-alcoholic fatty liver disease is associated with greater risk of 30-day hospital readmission in the United States (U.S.).

INTRODUCTION AND OBJECTIVES: Data about 30-day readmission for patients with chronic liver disease (CLD) and their contribution to CLD healthcare burden are sparse. Patterns, diagnoses, timing and predictors of 30-day readmissions for CLD from 2010-2017 were assessed. MATERIALS AND METHODS: Nationwide Readmission Database (NRD) is an all-payer, all-ages, longitudinal administrative database, representing 35 million discharges in the US population yearly. We identified unique patients discharged with CLD including hepatitis B (HBV) and C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) from 2010 through 2017. Survey-weight adjusted multivariable analyses were used. RESULTS: From 2010 to 2017, the 30-day readmission rate for CLD decreased from 18.4% to 17.8% (p=.008), while increasing for NAFLD from 17.0% to 19. 9% (p<.001). Of 125,019 patients discharged with CLD (mean age 57.4 years, male 59.0%) in 2017, the most common liver disease was HCV (29.2%), followed by ALD (23.5%), NAFLD (17.5%), and HBV (4.3%). Readmission rates were 20.5% for ALD, 19.9% for NAFLD, 16.8% for HCV and 16.7% for HBV. Compared to other liver diseases, patients with NAFLD had significantly higher risk of 30-day readmission in clinical comorbidities adjusted model (Hazard ratio [HR]=1.08 [95% confidence interval 1.03-1.13]). In addition to ascites, hepatic encephalopathy, higher number of coexisting comorbidities, comorbidities associated with higher risk of 30-day readmission included cirrhosis for NALFD and HCV; acute kidney injury for NAFLD, HCV and ALD; HCC for HCV, and peritonitis for ALD. Cirrhosis and cirrhosis-related complications were the most common reasons for 30-day readmission, followed by sepsis. However, a large proportion of patients (43.7% for NAFLD; 28.4% for HCV, 39.0% for HBV, and 29.1% for ALD) were readmitted for extrahepatic reasons. Approximately 20% of those discharged with CLD were readmitted within 30 days but the majority of readmissions occurred within 15 days of discharge (62.8% for NAFLD, 63.7% for HCV, 74.3% for HBV, and 72.9% for ALD). Among readmitted patients, patients with NAFLD or HCV readmitted ≤30-day had significantly higher costs and risk of in-hospital mortality (NAFLD +5.69% change [95% confidence interval, 2.54%-8.93%] and odds ratio (OR)=1.58 [1.28-1.95]; HCV +9.85% change [95%CI:6.96%-12.82%] and OR=1.31, 1.08-1.59). CONCLUSIONS: Early readmissions for CLD are prevalent causing economic and clinical burden to the US healthcare system, especially NAFLD readmissions. Closer surveillance and attention to both liver and extrahepatic medical conditions immediately after CLD discharge is encouraged.

Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study.

BACKGROUND: There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD. METHODS: Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality. RESULTS: Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64-1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55-2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68-2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13-1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29-2.30, p = 0.71). CONCLUSIONS: Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy.

Liver Stiffness Is a Predictor of Rebleeding in Patients With Hepatitis B-Related Cirrhosis: A Real-World Cohort Study.

Background: Esophageal vein rebleeding is a life-threatening complication of liver cirrhosis. However, the role of non-invasive methods that were developed to evaluate the severity of chronic liver disease, especially in rebleeding, remains unclear. Aims: To evaluate the performance of liver stiffness and non-invasive fibrosis scores in predicting esophageal vein rebleeding in hepatitis B virus (HBV) cirrhotic patients. Methods: A prospective analysis of 194 HBV patients between 2017 and 2021 was performed. Receiver operating characteristic (ROC) curves and time-dependent ROC curves were used to assess the power for predicting rebleeding with non-invasive fibrosis score and liver stiffness. Results: During the median follow-up time of 68.28 weeks, 55 patients experienced rebleeding. In the entire cohort, the area under the ROC curve for liver stiffness measurement (LSM) predicting for rebleeding was 0.837, with a cut-off value of 17.79 kPa, and the time-dependent ROC curve also showed stable prediction performance of LSM. The predictive ability of the non-invasive fibrosis score was less than that of LSM, and there were statistical differences. Moreover, patients using non-selective beta-blockers and HBV DNA-negative patients experienced significantly reduced rebleeding. Conclusions: Compared with non-invasive fibrosis scores, LSM can more simply and accurately predict rebleeding events of hepatitis B liver cirrhosis.

A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can be treated effectively if detected at an early stage. Recommended surveillance strategies for at-risk patients include ultrasound with or without α-fetoprotein (AFP), but their sensitivity is suboptimal. We sought to develop a novel, blood-based biomarker panel with improved sensitivity for early-stage HCC detection. METHODS: In a multicenter, case-control study, we collected blood specimens from patients with HCC and age-matched controls with underlying liver disease but without HCC. Ten previously reported methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins, including AFP, were assayed and analyzed by a logistic regression algorithm to predict HCC cases. The accuracy of the multi-target HCC panel was compared with that of other blood-based biomarkers for HCC detection. RESULTS: The study included 135 HCC cases and 302 controls. We identified a multi-target HCC panel of 3 MDMs (HOXA1, EMX1, and TSPYL5), B3GALT6 and 2 protein markers (AFP and AFP-L3) with a higher sensitivity (71%, 95% CI: 60-81%) at 90% specificity for early-stage HCC than the GALAD score (41%, 95% CI: 30-53%) or AFP ≥7.32 ng/mL (45%, 95% CI: 33-57%). The AUC for the multi-target HCC panel for detecting any stage HCC was 0.92 compared with 0.87 for the GALAD score and 0.81 for AFP alone. The panel performed equally well in important subgroups based on liver disease etiology, presence of cirrhosis, or sex. CONCLUSIONS: We developed a novel, blood-based biomarker panel that demonstrates high sensitivity for early-stage HCC. These data support the potential for liquid biopsy detection of early-stage HCC to clinically benefit at-risk patients. This study was registered on ClinicalTrials.gov (NCT03628651).

Surveillance of hepatocellular carcinoma in cirrhotic patients: Current knowledge and future directions.

Patients with cirrhosis are at the highest risk to develop hepatocellular carcinoma (HCC), with a variable annual risk of 1-8%. Currently, biannual abdominal ultrasound (USG) with or without alpha fetoprotein (AFP) is the recommended HCC surveillance strategy of major professional liver societies for all cirrhotic patients. However, the effectiveness of USG and AFP has been a sprawling subject of debate due to conflicting results and the low quality of the evidence. The role of cross-sectional imaging is controversial due to potential harm and cost-effectiveness concerns. Several novel serum biomarkers have been introduced for HCC screening, but have yet to be validated for various geographic regions. A risk-stratified algorithm is needed to increase the yield of HCC surveillance by distinguishing a high-risk group that requires more intense screening with cross-sectional imaging and serum biomarkers, and a low-risk group, where the standard surveillance strategy is continued. In this review, the strengths and concerns related to standard USG-based surveillance strategy are discussed, as well as efforts to increase the effectiveness of surveillance.

Transjugular Intrahepatic Portosystemic Shunt does not affect the efficacy and safety of direct-acting antivirals in patients with advanced cirrhosis: A real-life, case-control study.

BACKGROUND: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a well-established treatment for complications of portal hypertension. AIMS: To analyze the impact of TIPS on virologic response and safety profile in patients treated with direct-acting antivirals (DAAs). METHODS: We analyzed data from HCV-positive cirrhotic patients treated with DAAs. Twenty-one patients with previous TIPS placement were compared with 42 matched subjects without TIPS. Logistic regression was used to identify predictors of hepatic function worsening and adverse events. RESULTS: No differences were found between the two groups in particular regarding sustained virologic response (92.5 and 97.6% in TIPS vs no-TIPS, p = 0.559). Model for End-stage Liver Disease (MELD) of both TIPS and no-TIPS groups declined from baseline to week 24 of follow-up (from 12.5 ±â€¯3.5 to 10.8 ±â€¯3.4 and from 11.1 ±â€¯3.5 to 10.3 ±â€¯3.4, p = 0.044 and 0.025). There were no differences in adverse event rates. At univariate analysis, age was associated with MELD increase from baseline to week 24 (OR 1.111, 95% CI 1.019-1.211, p = 0.017), and patients with higher baseline MELD developed serious adverse events more frequently (OR 0.815, 95% CI 0.658-1.010, p = 0.062). Patients with or without TIPS did not show differences in transplant-free survival. CONCLUSION: TIPS placement does not affect virologic response and clinical outcome of patients receiving DAAs.

Prognostic Implications of Minimal/Covert Hepatic Encephalopathy: Large-scale Validation Cohort Studies.

Minimal or Covert Hepatic Encephalopathy (MHE/CHE), the preclinical phase of Hepatic Encephalopathy (HE), is strongly associated with poorer Quality of Life (QOL), Overt HE (OHE), and death. Several diagnostic tests have been developed that have prognostic value in predicting clinical outcomes such as OHE, cirrhosis progression, and death. However, dispute among clinicians and HE researchers have kept its application largely underutilized. Current issues contributing to the confusion include: lack of a formal definition for CHE, uncertainty of which diagnostic tools to use, and whether one or two abnormal tests are required for a diagnosis. Due to this misunderstanding, the aims of this review were to consolidate large-scale (n ≥ 100) validation studies in order to discuss these obstacles and make recommendations for improving our approach to MHE/CHE. The studies included in this review are a great resource for initiating a unified effort for advancement in HE, and as such, it is our hope that this will drive progress toward common goals that will permanently improve the lives of patients with cirrhosis.

Cirrosis hepática y fibrosis quística en un paciente pediátrico / Hepatic cirrhosis and cystic fibrosis in pediatric patients

RESUMEN Fundamento: aunque la enfermedad hepática crónica como complicación de la fibrosis quística ha sido eclipsada por otros signos y síntomas más obvios a nivel respiratorio y pancreático, constituye la segunda causa de muerte en los pacientes con fibrosis quística. Objetivo: presentar el caso de una transicional de tres años con hepatomegalia y pruebas analíticas hepáticas alteradas como manifestaciones iniciales de la fibrosis quística. Caso clínico: paciente de tres años, femenina, con historia de distensión abdominal, hepatomegalia y desnutrición. Por esta sintomatología es remitida a la consulta de Gastroenterología. Conclusiones: se debe sospechar la fibrosis quística en pacientes pediátricos con hepatopatía crónica. Se observó mejoría clínica de las manifestaciones respiratorias y del estado nutricional, sin embargo, la hepatopatía evolucionó a la cirrosis hepática establecida.

ABSTRACT Background: although the chronic hepatic illness as complication of the cystic fibrosis has been eclipsed by other signs and more obvious symptoms at breathing and pancreatic level, is the second cause of death in the patients with cystic fibrosis. Objective: to present the case of a three year-old transitional one with hepatomegaly and hepatic analytic tests altered as initial manifestations of the cystic fibrosis. Clinical case: a three-year old, female patient with history of abdominal distension, hepatomegaly, and malnutrition. For this symptoms, she is remitted to the Gastroenterology consultation. Conclusions: the cystic fibrosis should be suspected in pediatric patient with chronic hepatic diseases. Clinical improvement of the breathing manifestations was observed and of the nutritional state, however the chronic hepatic disease evolved to the established hepatic cirrhosis.

Nontumorous Portal Vein Thrombosis in Liver Cirrhosis: Possible Role of ß-Blockers.

OBJECTIVE: Nonselective ß-blockers (NSBB) are used in liver cirrhosis (LC) to prevent variceal bleeding because they decrease portal pressure. A main risk factor for the development of portal vein thrombosis (PVT) in LC is decreased portal vein inflow velocity. The aim of our study was to examine retrospectively the incidence of PVT and its correlation with the use of ß-blockers in a cohort of LC patients. SUBJECTS AND METHODS: Data from 230 LC patients (90% Child-Pugh class A), who had been followed up for at least 5 years, were reviewed. The diagnosis of PVT was made by ultrasound. The presence of PVT was evaluated with multiple logistic regression analysis where the independent variables were those significant in the univariate analysis. RESULTS: The prevalence of PVT at baseline was 4.5%, and the incidence was 4.3% at 5 years; among the subjects taking ß blockers, 46.4% were taking NSBB. A total of 19 PVT cases were found. Grade of esophageal varices (p < 0.01), PLT (p < 0.003), INR (p < 0.03), spleen diameter (p < 0.001) and PLT/spleen ratio (p < 0.0005) were significantly associated with PVT. The use of NSBB indicated a higher risk of PVT compared to selective ß-blockers (SBB) (p < 0.05). In logistic regression analysis only the grade of esophageal varices was significant (p < 0.02). Univariate analysis of patients taking ß-blockers showed an association of PVT with grade of esophageal varices (p < 0.01), CP class (p < 0.02), AST (p < 0.03), ALT and albumin (p < 0.02), PLT count and PLT/LD (p < 0.03), longitudinal diameter of the spleen (p < 0.005), ascites (p < 0.05), portal vein (p < 0.0001) and NSBB (OR 8.1; 95% CI 1.7-38.8). CONCLUSION: NSBB seem to play a role in PV thrombogenesis. Further studies are needed, especially in decompensated LC patients.

Pathogenesis of solute-free water retention in experimental ascitic cirrhosis: is vasopressin the only culprit?

Catecholamines trigger proximal tubular fluid retention and reduce renal excretion of solute-free water. In advanced cirrhosis, non-osmotic hypersecretion of vasopressin (antidiuretic hormone or ADH) is considered the cause of dilutional hyponatraemia, but ADH V2 receptor antagonists are not beneficial in long-term treatment of ascites. To test the hypothesis that water retention in experimental ascitic cirrhosis might depend primarily on adrenergic hyper-function, hormonal status, renal function and tubular free-water reabsorption (TFWR) were assessed in six groups of rats with ascitic cirrhosis: rats with cirrhosis due to 13-week CCl4 (carbon tetrachloride) administration (group G1); cirrhotic rats receiving daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K(+)-canrenoate) from the 11th to the 13th week of CCl4 (G2), diuretics associated with guanfacine oral prodrug (α2A-adrenergic receptor agonist and sympatholytic agent) at 2 (G3), 7 (G4) or 10 (G5) mg/kg, or with SSP-004240F1 (V2 receptor antagonist) at 1 mg/kg (G6). Natriuresis was lower in G1 than in G2, G4 and G6 (all P<0.05). Guanfacine, added to diuretics (i.e. G3 compared with G2), reduced serum noradrenaline from 423±22 to 211±41 ng/l (P<0.05), plasma renin activity (PRA) from 35±8 to 9±2 ng/ml/h (P<0.05) and TFWR from 45±8 to 20±6 µl/min (P<0.01). TFWR correlated with plasma aldosterone (r=0.51, P<0.01) and urinary potassium excretion (r=0.90, P<0.001). In ascitic cirrhosis, reduced volaemia, use of diuretics (especially furosemide) and adrenergic hyper-function cause tubular retention of water. Suitable doses of sympatholytic agents are effective aquaretics.

Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF).

BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor (sMR) and related them to the short-(1-3 months) and long-term (6 months) mortality in the cirrhosis patients of the CANONIC study. METHODS: Eighty-six cirrhosis patients had no ascites and no ACLF, 580 had ascites but no ACLF; 100, 66, and 19 had ACLF-grade-I (ACLF-I), ACLF-II, and ACLF-III, respectively. The patients' clinical course was registered and their MELD, CLIF-C Acute Decompensation (AD), and CLIF-C ACLF-scores computed at inclusion. RESULTS: We found a stepwise increase (p<0.001) in median sCD163 (5.68 (IQR: 3.86-9.60); 8.26 (5.02-12.34); 9.50 (5.37-17.91); 15.68 (10.12-19.42); 20.18 (15.26-32.20) mg/L) and sMR (0.60 (0.40-0.84); 0.81 (0.57-1.12); 0.81 (0.61-1.26); 1.17 (0.89-1.62); 1.41 (1.14-1.79)mg/L) with increasing grades of ACLF. Both sCD163 and sMR were independently associated with short and long-term mortality and showed equal or higher predictive accuracy than MELD, CLIF-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index: 0.74 (0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality (C-index: 0.80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform of the clinical scores improved the prognostic performance beyond that of the original scores.

Fasting Blood Ammonia Predicts Risk and Frequency of Hepatic Encephalopathy Episodes in Patients With Cirrhosis.

BACKGROUND & AIMS: There is controversy over the use of measuring blood levels of ammonia (NH3) in the management of patients with overt hepatic encephalopathy (HE). METHODS: We performed a retrospective analysis of data from a randomized, double-blind study of 178 patients with cirrhosis given glycerol phenylbutyrate (an NH3-lowering agent) or placebo for 16 weeks. Blood samples were collected at baseline and on study days 7 and 14 and NH3 levels were measured. The probabilities of having an HE episode, based on ammonia values, were modeled using binary logistic regression. A Cox proportional model was used to determine the risk of HE episodes in patients with baseline fasting NH3 levels ≤1.5-fold the upper limit of normal (ULN) versus patients with fasting NH3 levels >1.5-fold the ULN. RESULTS: The risk and frequency of HE episodes and HE-related hospitalizations correlated with baseline (mean, 51 ± 6 µmol/L; ULN, 35 µmol/L) and on-study fasting levels of NH3, and increased sharply at levels >1.5-fold the ULN. Regardless of baseline level, NH3 exposure and the relative risk of HE episodes were decreased by glycerol phenylbutyrate. CONCLUSIONS: In analysis of data from a phase 2 study of the effects of glycerol phenylbutyrate in patients with cirrhosis, we found that fasting levels of NH3 in blood can identify patients at risk for HE-related morbidity. Patients with HE might benefit from NH3-lowering therapy. ClinicalTrials.gov no: NCT 00999167.

Dose-dependency of clonidine's effects in ascitic cirrhotic rats: comparison with α1-adrenergic agonist midodrine.

BACKGROUND & AIMS: Sympathetic nervous system (SNS) activation decreases response to diuretics, but both α1-adrenoceptor agonists and sympatholytic α2-adrenoceptor agonists are recommended in the management of ascitic cirrhosis. We intend to compare the effects of increasing doses of clonidine (α2-agonist) vs. midodrine (α1-agonist) in advanced cirrhosis. METHODS: Renal function, mean arterial pressure (MAP), and hormonal status were measured in rats with ascitic cirrhosis due to 13-week CCl(4) administration (groups G1-G5), in control rats (Gc), and in rats with ascitic cirrhosis untreated (G6) or treated with daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K(+) -canrenoate during the 11(th) -13(th) weeks of CCl(4)) (G7). G1-G5 cirrhotic rats received daily, during the 11(th)-13(th) CCl(4) weeks: clonidine 0.3 µg only (G1), diuretics + clonidine 0.2 (G2), 0.5 (G3) or 1 µg (G4), and diuretics + midodrine 1 mg/kg b.w. (G5). RESULTS: Cirrhotic rats in G1 or G2 had higher glomerular filtration rate, renal plasma flow and natriuresis than cirrhotic rats treated with diuretics (G7) (all P < 0.05). The addition of clonidine 0.2 µg to diuretics (G2 vs. G7) reduced serum norepinephrine (169 ± 71 ng/L vs. 523 ± 88 ng/L) and plasma renin activity (12 ± 3 ng/ml/h vs. 25 ± 5 ng/ml/h) (all P < 0.05). Midodrine did not improve the renal performance in ascitic rats treated with diuretics. In comparison to absolute cirrhotic controls (G6), MAP was lower in G4 and higher in G5 (all P < 0.05). CONCLUSION: Low-dose α2-agonists improve natriuresis and reduce SNS function and hyper-aldosteronism without affecting arterial pressure in experimental ascitic cirrhosis treated with diuretics.

Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients.

BACKGROUND AND AIM: The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. METHODS: A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). RESULTS: Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14-4.85], P = 0.02), hepatic complications (HR 2.04, [1.16-3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05-4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96-4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). CONCLUSION: The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.

Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®).

BACKGROUND & AIMS: The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. METHODS: The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. RESULTS: Of the 1312 patients without a history of complications, varices had occurred after 10 years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6-2.8]), and severe complications in 25 (F4.3 3.7% [1.8-5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5-5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71-0.90]; p<0.0001) and (n=8/844; AUROC=0.82 [0.72-0.89]; p<0.0001) respectively. Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p=0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p=0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2-9.1]) including 19 HCC (5.8% [2.6-9.0]) and 10 with varices (2.6% [0.8-4.4]). Of the 138 responders with advanced fibrosis, only 31% (15-47%) had fibrosis regression. CONCLUSIONS: FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.

Diabetes mellitus como complicación de la cirrosis hepática. Hospital Territorial Docente Mario Muñoz Monroy. 2003-2013 / Mellitus as a complication of liver cirrhosis. Teaching Territorial Hospital Mario Muñoz Monroy. 2003-2013

La cirrosis hepática se encuentra dentro de las primeras 10 causas de muerte en Cuba. Además, constituye un problema de salud a escala mundial. Las complicaciones que se presentan como consecuencia de la misma agravan el pronóstico reservado de la enfermedad. Con el objetivo de determinar la frecuencia de diabetes mellitus como una de dichas complicaciones, se realizó un estudio descriptivo retrospectivo a 27 pacientes cirróticos, que se siguieron en la consulta externa de Gastroenterología, del Hospital Territorial Docente Mario Muñoz Monroy, del municipio de Colón, Matanzas, en el período de enero de 2003 hasta enero de 2013. El 77,8 % de los pacientes fueron hombres, el 51,85 % presentaron cirrosis de causa alcohólica, y un 25,92 % de causa viral. En el 22,2 % de los cirróticos se diagnosticó diabetes en la evolución de su enfermedad. Se concluyó que la diabetes mellitus tiene una alta frecuencia como complicación, que incide en la historia natural de un paciente con cirrosis hepática. Se recomendó la pesquisa sistemática de esta enfermedad en el seguimiento de rutina de los pacientes cirróticos.

Liver cirrhosis is among the first 10 causes of death in Cuba. It is also a health problem at the world level. The complications presented as a consequence of this disease increase its reserved prognosis. With the objective of determining the Diabetes Mellitus frequency as one of those complications, a descriptive retrospective study was carried out in 27 cirrhotic patients followed in the Gastroenterology outpatient consultation of the Teaching Territorial Hospital Dr. Mario Muñoz Monroy, municipality of Colón, Matanzas, in the period from January 2003 to January 2013. 77,8 % of the patients were men; 51,9 % presented alcoholic-caused cirrhosis and 25,9 % of them viral-caused cirrhosis; in 22,2 % of the cirrhotic patients, diabetes was diagnosed in the evolution of their disease. We arrived to the conclusion that Diabetes Mellitus shows a high frequency as a complication influencing the natural history of patients with liver cirrhosis. We recommended systematically screening this disease in the cirrhotic patients’ routine follow-up.

Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®).

BACKGROUND & AIMS: FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of critical steps defined by occurrence of cirrhosis without complications (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or jaundice). METHODS: The updated individual data of 3927 patients (1046 cirrhotics) without complications at baseline were pooled from three prospective cohorts called "EPIC", "Paris", and "Bordeaux" cohorts. RESULTS: At 5 years, among 501 patients without varices at baseline (F4.1) varices occurred in 19 patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance (AUROC) of FT was 0.77 (0.66-0.84; p<0.001). At 10 years severe complications occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on treatment) of severe complications [AUROC 0.79 (76-82); p<0.0001], including primary liver cancer [AUROC 0.84 (80-87); p<0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p<0.0001], including primary liver cancer [AUROC 0.86 (81-90); p<0.0001]. CONCLUSIONS: FibroTest™ and TE increase were associated with the occurrence of all severe complications including hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding. FibroTest™ increase was also associated with the occurrence of esophageal varices.