Degree Of Liver Disease Research Articles

HBV Biomarkers and Their Role in Guiding Treatment Decisions.

Over 300 million individuals worldwide are chronically infected with hepatitis B virus and at risk for progressive liver disease. Due to the lack of a therapy that reliably achieves viral elimination and the variability of liver disease progression, treatment decisions are guided by the degree of liver disease and viral biomarkers as the viral life-cycle is well characterized and largely conserved between individuals. In contrast, the immunological landscape is much more heterogeneous and diverse and the measurement of its components is less well standardized. Due to the lack of a universal and easily measurable set of biomarkers, clinical practice guidelines remain controversial, aiming for a balance between simplifying treatment decisions by reducing biomarker requirements and using all available biomarkers to avoid overtreatment of patients with low risk for disease progression. While approved therapies such as nucleos(t)ide analogs improve patient outcomes, the inability to achieve a complete cure highlights the need for novel therapies. Since no treatment candidate has demonstrated universal efficacy, biomarkers will remain important for treatment stratification. Here, we summarize the current knowledge on virological and immunological biomarkers with a specific focus on how they might be beneficial in guiding treatment decisions in chronic hepatitis B.

Interaction between coagulation and inflammatory system in liver disease: re-focus on hematological markers.

Aim: This study uses blood routine, coagulation and biochemical indicators to explore the relationship between the hematological parameters of patients with various types of liver diseases.Methods: The Kruskal-Wallis, Chi-squared and Fisher exact tests were used to compare the hematological parameters and clinical characteristics of three groups of patients with different degrees of liver disease. Spearman correlation analysis is used to analyze the correlation between two continuous variables. The logistic regression model evaluated the odds ratio between variables and disease changes. Receiver operating characteristic curve analysis was used to understand the predictive value of each index in relation to the progress of liver disease.Results: There are differences in inflammation and coagulation profiles among different types of liver diseases and there is a correlation between them. In addition to the traditional marker α-fetoprotein, the inflammatory marker c-reactive protein and the coagulation marker D-dimer also have good diagnostic value for liver injury.Conclusion: The coagulation and inflammation systems interact, are connected and play essential roles in the liver.

The Role of Bone Marrow Mesenchymal Stem Cells and Adipose Tissue-Derived Stem Cells in the Treatment of Liver Failure: A Literature Review

Liver disease is a major health problem that endangers human health worldwide. Stem cells have the unique ability to morph or differentiate into different types of cells within the body. In this way, stem cells can be used to seek out damaged liver tissue and regenerate the organ itself. Mesenchymal stem cells are multipotent stem cells that can self-renew and differentiate into different cell types. In other words, mesenchymal stem cells can become a variety of different cell types including adipose tissue, cartilage, muscle, tendon/ligament, bone, neurons, and hepatocytes. Many studies have shown that Mesenchymal stem cells play an essential role in liver recovery, and further research has verified the preliminary effectiveness and safety of these therapies. types of liver disease that are most suitable for MSC application should be determined, and the preparation and engraftment of MSCs should be standardized. Stem cell-based therapies will emerge as an effective treatment strategy for liver diseases in now and the future. Researchers conduct an examination of articles that are in accordance with the issue to be studied. Articles used in literature review are obtained through the database of international journal providers through PubMed, we investigated six clinical studies and discussed what happened in these clinical studies and the extent of the effectiveness of stem cells in treatment and whether the degree of liver disease had a role in the effectiveness of stem cells, we also discussed the mechanism of stem cells in treatment. One of six articles proved that Zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells, One of six articles proved that infusion of allogeneic bone marrow-derived MSCs improving liver function and decreasing the incidence of severe infections. The rest articles proved that MSCs both Bone Marrow Stem cells (BMSCs) and Adipose Derived Stem Cells (ADSCs) are promising therapeutic agents for the liver fibrosis and cirrhosis treatment. In this review, we suggest that formulating and following treatment, Further studies are needed to determine the related mechanisms to enhance MSC efficacy.

Atypically located spider angioma

To the Editor,
 A spider angioma or spider naevus is a type of telangiectasis found slightly beneath the skin surface, often containing a central arteriole and many small vessels which radiate outwards like a spider's web. Applying pressure to the center of the lesion leads to fading of the lesion. Spider angioma is a common presentation of liver cirrhosis, especially alcoholic cirrhosis. Spider angiomas are found only in the distribution of the superior vena cava, and are thus commonly found on the face, neck, upper chest and upper arm. Spider angioma is rarely observed on hand (1, 2). Here, we report a a very rare case with spider angioma on back of hand.
 A 54-year-old male patient admitted to our clinic with icterus and ascites. The patient had a diagnosis of alcoholic liver cirrhosis one month before. On physical examination, he had icterus and ascites. He had spider angiomas on his back, neck and on the back of his right hand, just proximal to second metacarpophalangeal joint (Figure 1). The patient’s Child Turcotte Pugh score (CTP) and model for end stage liver disease (MELD) scores were 12 and 22, respectively. Abdomen ultrasound showed cirrhosis with massive ascites. Endoscopy revealed grade 1 esophageal varices and portal hypertensive gastropathy. The patient gave written consent regarding this article.
 Spider angioma appears frequently in alcoholic cirrhotic or noncirrhotic alcoholic liver diseases with deuteriation of liver functions. Although, the exact cause of SA is not known, there have been many theories of possible etiologic factors such as disturbance of sex hormones (increased level of luteinizing hormone, decreased level of testosterone and a higher estradiol/testosterone ratio), angiogenesis, vasodilation, alcohol abuse, hyperdynamic circulation state, and liver dysfunction[3, 4]. The number and size of SA are correlated with the degree of liver disease (1, 3, 4). 
 Our patient was a heavy drinker and had alcoholic liver cirrhosis with high CTP and MELD score. Although, our patient had multiple telangiectasias, it is a very rare finding of SA, observed on back of hand.

Sleep disruption in nonalcoholic fatty liver disease: What is the role of lifestyle and diet?

Patients with nonalcoholic fatty liver disease (NAFLD) have sleep disruption. The aim of this study is to understand how underlying factors such as diet, degree of liver disease and morningness-eveningness tendencies contribute to this sleep disruption. Patients with NAFLD were recruited from liver clinics at a University and Veterans Affairs practice. Patients with decompensated cirrhosis were excluded. Patients completed self-reported surveys to evaluate sleep disturbance using the Epworth Sleepiness Scale (ESS) and chronotype (circadian preference) using the morningness-eveningness questionnaire (MEQ). Information on occupation, physical activity and dietary intake were collected at clinic intake. Dietary intake was evaluated via food-frequency questionnaire and analyzed as individual categories or grouped on the basis of dietary composition. A 54 patients completed the survey; 37% were female. Median ESS was 8 ± 4.2 and 37% of NAFLD patients were found to have sleep disturbance as defined by ESS >10. Sleep disturbance was common in NAFLD regardless of the liver disease stage. Dietary factors, including higher added sugar (P = 0.01), candy intake (P = 0.01), elevated Ferritin level (P = 0.04) and elevated platelet count (P = 0.05), were significantly associated with sleep disturbance. Chronotype, time to sleep, and duration of sleep were not associated with sleep disruption. Sleep disruption is present in NAFLD regardless of underlying cirrhosis. Interventions aimed at improving dietary and lifestyle practices such as reduced sugar intake may help mitigate the risk for sleep disruption in NAFLD. Further longitudinal studies are needed to further delineate these links.

Phase angle and non-alcoholic fatty liver disease before and after bariatric surgery.

BACKGROUNDObesity is a global health problem that is continuing to increase in the young population. In Brazil, the frequency of obesity in 2018 was 19.8%. Several comorbidities are directly associated with obesity, such as non-alcoholic fatty liver disease (NAFLD), which is considered the most common liver disorder in Western countries and affects up to 46% of adults. Bariatric surgery is effective in treating obesity and can improve NAFLD; however, the effect of bariatric surgery on body composition, phase angle (PA), and improving NAFLD needs to be further studied.AIMTo analyze the PA in the postoperative period of bariatric surgery and to correlate it with changes in body composition and liver disease.METHODSThis study is a retrospective cohort study of the analysis of the medical records of patients undergoing bariatric surgery in a reference center of a teaching hospital in Porto Alegre over a 2-year period. Patients older than 18 years whose record contained all information relevant to the study were included. The data analyzed were body composition and PA through electrical bioimpedance and NAFLD through liver biopsy in the pre- and postoperative period. The level of significance adopted for the statistical analyses was 5%.RESULTSWe evaluated 379 patients with preoperative data. Regarding PA, 169 patients were analyzed, and 33 patients had liver biopsy pre- and postoperatively with NAFLD information. In total, 79.4% were female, with a mean age of 39.1 ± 10.6 years. The average body mass index (BMI) was 45.9 ± 7.5 kg/m². The PA showed a mean of 5.8 ± 0.62° in the preoperative period and a significant reduction in the postoperative period. A postoperative reduction in body composition data (skeletal muscle mass, fat percentage, fat mass, body cell mass, BMI and visceral fat area) was shown as well. Regarding liver disease, all patients presented a reduction in the degrees and stages of liver disease in the postoperative period, and some had no degree of liver disease at all. CONCLUSIONPA decreased after bariatric surgery, with a direct correlation with weight loss and changes in body composition. The decrease in PA was not correlated with the improvement in NAFLD.

Periostin Circulating Levels and Genetic Variants in Patients with Non-Alcoholic Fatty Liver Disease.

Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N. = 74; 10 with hepatocellular carcinoma, HCC) plasma periostin concentrations were analyzed. POSTN haplotype analysis was based on rs9603226, rs3829365, and rs1029728. Hepatitis C patients (N. = 81, 7 HCC) and healthy subjects (N. = 27) were used as controls. The median plasma periostin concentration was 11.6 ng/mL without differences amongst groups; it was not influenced by age, liver fibrosis or steatosis. However, possession of haplotype two (rs9603226 = G, rs3829365 = C, rs1028728 = A) was associated with lower circulating periostin compared to other haplotypes. Moreover, periostin was higher in HCC patients. At multivariate analysis, HCC remained the only predictor of high periostin. In conclusion, plasma periostin concentrations in Caucasians NAFLD patients are not influenced by the degree of liver disease, but are significantly higher in HCC. Genetically-determined differences may account for some of the variability. These data suggest extreme caution in predicting a possible future role of periostin antagonists as a rational therapeutic alternative for NAFLD, but show a potential periostin role in the management of NAFLD-associated HCC.

Shanxian granule ameliorates diethylnitrosamine-induced precancerous lesions in liver by regulating inflammatory mediators

To explore the effects of Shanxian Granules (SXG) on diethylnitrosamine (DEN) -induced precancerous lesions in rats and its possible molecular mechanism. A total of 50 male SD rats (190±10 g) were randomly divided into five groups. control group, DEN group, SXG low dose group, SXG medium dose group and SXG high dose group. The control group received saline injection. The precancerous liver cirrhosis group received 50mg/kg DEN via intraperitoneal injection twice a week for 16 weeks. The indexes of liver function (ALT, AST and GGT) were measured by blood sampling. HE staining was used to observe pathological changes of liver tissues. The levels of IL-6 and TNFα were measured by ELISA kits. Compared with the model group, the high (P<0.01) and middle dose (P<0.05) of SXG significantly reduced the damage of liver function and ameliorated the degree of liver disease, such as hepatic fibrosis. In addition, SXG significantly decreased the levels of IL-10 and TNFα in the liver of DEN-induced precancerous lesions. In conclusion, SXG can effectively and dose-dependently alleviate the morphological changes of rat liver precancerous lesions. and the underlying protective mechanism of SXG may be by inhibiting the release of inflammatory mediators, such as IL-6 and TNF-α.

Local care and treatment of liver disease (LOCATE) – A cluster-randomized feasibility study to discover, assess and manage early liver disease in primary care

BackgroundChronic liver disease is an escalating problem both in the United Kingdom and worldwide. In the UK mortality rates have risen sharply over the previous 50 years predominantly due to alcohol, however the increasing prevalence of non-alcohol related fatty liver disease both in the UK and elsewhere is also of concern. Liver disease develops silently hence early detection of fibrosis is essential to prevent progression. Primary care presents an opportunity to identify at risk populations, however assessment largely comprises of indirect markers of fibrosis which have little prognostic value. We hypothesised that setting up nurse-led primary care based liver clinics using additional non-invasive testing would increase the number of new diagnoses of liver disease compared to usual care.MethodsThis was a prospective, cluster randomised feasibility trial based in urban primary care in Southampton, United Kingdom. 10 GP practices were randomised to either intervention (liver health nurse) or control (care as usual). Pre recruitment audits were carried out in each practice to ascertain baseline prevalence of liver disease. Participants were subsequently recruited in intervention practices from July 2014-March 2016 via one of 3 pathways: GP referral, nurse led case finding based on risk factors or random AUDIT questionnaire mailouts. Liver assessment included the Southampton Traffic Light test (serum fibrosis markers HA and P3NP) and transient elastography (FibroScan). Cases were ascribed as ‘no fibrosis’, ‘liver warning’, ‘progressive fibrosis’ or ‘probable cirrhosis’. Post recruitment audits were repeated and incident liver diagnoses captured from July 2014-September 2016. Each new diagnosis was reviewed in a virtual clinic by a consultant hepatologist.Findings910 participants were seen in the nurse led clinic—44 (4.8%) probable cirrhosis, 141 (15.5%) progressive fibrosis, 220 (24.2%) liver warning and 505 (55.5%) no evidence of liver fibrosis. 450 (49.5%) cases were due to NAFLD with 356 (39.1%) from alcohol. In the 405 with a liver disease diagnosis, 136 (33.6%) were referred by GP, 218 (53.8%) from nurse led case finding and 51 (12.6%) from the AUDIT mailout. 544 incident cases were identified in the intervention arm compared to 221 in the control arm in the period July 2014-September 2016 (adjusted odds ratio 2.4, 95% CI 2.1 to 2.8).ConclusionsThe incorporation of a liver health nurse into GP practices was simple to arrange and yielded a much higher number of new diagnoses of liver disease compared to usual care. Nearly half of all participants recruited had a degree of liver disease. Nurse led case finding and GP referrals were most effective compared to AUDIT questionnaire mailouts in an urban population in identifying unknown disease. Utilising study and previous data allowed quick and effective virtual review by a hepatologist. Identifying those who are at risk of liver disease from harmful alcohol use remains a challenge and needs to be addressed in future work.

Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection

Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins <1 cm and being beyond the Milan criteria. HCC late recurrence at univariate analysis was associated with esophageal varices (hazard ratio [HR] 3.321, 95% CI 1.564-7.053), spleen length (HR 3.123, 95% CI 1.377-7.081), platelet/spleen length ratio if <909 (HR 2.170, 95% CI 1.026-4.587), LSM (HR 1.036, 95% CI 1.005-1.067), SSM (HR 1.046, 95% CI 1.020-1.073). HCC late recurrence at multivariate analysis was independently associated only with SSM (HR 1.046, CI 1.020-1.073). Late HCC recurrence-free survival was significantly different according to the SSM cut-off of 70 kPa (p = 0.0002). SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

Safety and Effectiveness of Suture-mediated Arterial Closure Device in Hepatocellular Carcinoma Patients Who Underwent Drug-Eluting Beads Transarterial Chemoembolization

The number of transarterial percutaneous procedures has risen over the years, consequently reducing puncture site related complications has become a necessity. To this end, the use of arterial closure devices has been growing progressively and their benefits have become a focus of research. The purpose of this study is to assess the safety and effectiveness of a suture-mediated closure device, Perclose ProGlide® (Abbott Vascular, Redwood City, CA), in patients with liver disease and hepatocellular carcinoma who underwent transarterial liver chemoembolization with drug-eluting beads. A cohort of 253 hepatocellular carcinoma patients who underwent 449 procedures of transarterial liver chemoembolization with drug-eluting beads using the Perclose Proglide device was prospectively studied. The main endpoints evaluated were the technical success of the device, defined as complete hemostasis achieved within 3min after the closure, and the incidence of puncture-site complications. The secondary endpoints evaluated were the correlation between epidemiological factors, coagulation profile and degree of liver disease, and the occurrence of complications. Technical success was achieved in 96% of the cases. Among patients who underwent repeated procedures using the same vascular access, this rate was 95.3%. Puncture-site complications were observed in 7 procedures (1.56%); 4 (0.89%) were due to hemorrhage, 2 (0.44%) hematomas and 2 (0.44%) pseudoaneurysms; 2 (0.44%) due to limb ischemia; and 1 (0.22%) due to arterial dissection. Among them, 3 cases required intervention. The statistical analysis of demographic characteristics, Child-Pugh classification, and coagulation status did not show a significant correlation with the occurrence of complications. Of the 449 procedures, only 4 (0.89%) needed hospitalization due to puncture-site complications. The use of Perclose Proglide is safe and effective in patients with liver disease and hepatocellular carcinoma who underwent transarterial liver chemoembolization with drug-eluting beads.

Ultrasound Shear Wave Elastography as a Measure of Porcine Hepatic Disease in Right Heart Dysfunction: A Pilot Study

Patients with congenital heart disease with a pressure-overloaded right ventricle can develop liver disease and would benefit from non-invasive diagnostic modalities such as ultrasound shear wave elastography (US SWE). We sought to investigate the ability of US SWE to measure dynamic changes in liver stiffness with an acute fluid bolus in an animal model. Three piglets underwent surgical intervention to create a pressure-overloaded right ventricle and, 12 wk later, underwent US SWE, both pre- and post-intravenous infusion of a saline bolus. Ultrasound measures of shear modulus, velocity and attenuation were taken to characterize hepatic mechanical properties. Liver stiffness exhibited a dynamic component that increased after fluid bolus, although not reaching statistical significance with our small sample size, and these changes were greater in more diseased livers. US SWE may provide a promising non-invasive method for assessing dynamic changes in hydration status and degree of liver disease.

Hepatic Lipid Profiling in Fatty Liver Disease—Degree of Saturation Matters

Introduction: Hepatic lipids can take on several storage forms, which vary by degree of saturation. The health consequences of hepatic lipids may vary by storage type, in that polyunsaturated lipids may be favorable, while saturated lipids may be detrimental. The purpose of this study was to determine if the degree of hepatic lipid saturation is related to hallmark characteristics of obesity-related nonalcoholic fatty liver disease, including low exercise capacity and insulin resistance. Methods: Hepatic lipid profiles were measured using 1H-MRS in 30 adults (55 ± 13.4 years, 31 ± 5.5 kg/m2). Methyl, allylic, methylene, and diallylic peaks were quantified. Hepatic lipids were categorized by storage form, including polyunsaturation, unsaturation, and saturation indices. Explored health correlates include exercise capacity, 40 mU/m2 euglycemic-hyperinsulinemic clamps, and abdominal CT scans. Results: 20 participants met the diagnostic criteria for nonalcoholic fatty liver disease (total hepatic fat &amp;gt; 5%). Hepatic polyunsaturation index was positively related to absolute maximal oxygen uptake (r=0.41, P=0.04). In addition, hepatic saturation index was inversely related to clamp-derived skeletal muscle insulin sensitivity (r=-0.48, P=0.007). Discussion/Conclusion: We found that the hepatic polyunsaturation index was positivity related to exercise capacity, independent of body weight. Conversely, saturation index was inversely related to insulin sensitivity. These data show that the health consequences of hepatic fat vary by storage type. Insulin resistance is associated with a higher degree of saturation and a consequential lower degree of polyunsaturation. Thus, effective treatment strategies for nonalcoholic fatty liver disease should not only aim to reduce total hepatic lipid content, but also promote a shift in storage type, from saturation to polyunsaturation, in order to maximize metabolic benefit. Disclosure M.L. Erickson: None. J.M. Haus: None. C. Flask: None. J.P. Kirwan: None.

Effect of Meal Ingestion on Liver Stiffness and Controlled Attenuation Parameter

Background and Aims: Despite the increasing use of noninvasive methods for the assessment of liver fibrosis and steatosis, the effect of fasting and food intake on these parameters is not yet clear. Our aims were to evaluate the effect of food intake on liver stiffness (LS) (measured by transient elastography) and controlled attenuation parameter (CAP) in patients with different degrees of liver disease and healthy volunteers, and secondarily, to assess possible factors associated with variations of LS and CAP. Methods: We performed a prospective single-center study including patients with liver disease and healthy volunteers. LS and CAP were evaluated using FibroScan® (Echosens, Paris, France), before (fasting ≥8 h) and 30 min after intake of a standardized breakfast. We used common cutoffs for LS: > 7 kPa for significant fibrosis (F2 to F4) and > 11 to 14 kPa (mean 12.5 kPa) for cirrhosis. Results: Fifty-nine (72%) patients with liver disease and 22 (28%) healthy volunteers were included. LS significantly increased 30 min after food intake (pre-meal 6.1 kPa [IQR: 4.7–9.8] vs. after-meal 6.8 kPa [IQR: 5.5–10.6]; p < 0.001). This difference was only significant in patients with chronic liver disease (p = 0.02) and not in healthy volunteers (p = 0.106). CAP values did not increase significantly after food intake. Gender, body mass index, mass of body fat, lean body mass, and percent of body fat were not related with significant variations of LS and CAP values after meal intake. Conclusions: Significant variations of LS were observed after ingestion of a standard meal, which may have consequences for patient management. CAP values were not significantly affected by food intake. Therefore, we consider that before the isolated evaluation of CAP, it is not necessary to perform any fasting period.

Platelet Count Does Not Predict Bleeding in Cirrhotic Patients: Results from the PRO-LIVER Study.

Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child-Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800-1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11-3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16-3.62; P=0.013) independently predicted overall bleeding events. Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

Chapter 9 - Hepatic features of Wilson disease

In Wilson disease (WD) defective AT7B function leads to biliary copper excretion and pathologic copper accumulation, particularly in liver and brain, where it induces cellular damage. Liver disease most often precedes neurologic or psychiatric manifestations. In most patients with neurologic or psychiatric symptoms there is some degree of liver disease at the time of disease presentation. Hepatic manifestations of WD can be extremely variable. Patients with clinically asymptomatic WD are often found by family screening or identified on routine laboratory testing. Others may have a clinical picture of chronic active hepatitis or of end-stage liver disease with cirrhosis. A minority present with acute liver failure, often on the background of advanced fibrosis. Complications from liver disease may be related to portal hypertension and concomitant liver disease may accelerate the course of liver disease. Liver cancer may occur in patients with WD, most commonly when cirrhosis and inflammation are present. The prognosis of patients with WD is excellent, especially for those without cirrhosis at the time of diagnosis, but requires timely initiation of appropriate therapy specific for WD and for the patient's liver disease independent of WD.

New organ allocation policy in liver transplantation in the United States.

New organ allocation policy in liver transplantation in the United States.

Outcomes of abdominal surgery in patients with liver cirrhosis

Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery.

Epidemiological characteristics of bloodstream infections in patients with different degrees of liver disease.

Observational retrospective study to evaluate the etiology, the outcome and the risk factors of bloodstream infections (BSIs) in patients with liver disease. One hundred and forty-eight BSIs were diagnosed (infection rate: 0.60 per 100 days of hospital stay), 62 BSIs (41.9 %) were associated with Gram-positive bacteria (infection rate: 0.25 per 100 days of hospital stay) and 80 (54.4 %) with Gram-negative bacteria (infection rate: 0.32 per 100 days of hospital stay). Admission-associated mortality was higher in patients with BSI than in those without BSI (20.6 versus 5.0 %, p < 0.001). Patients with cirrhosis had an increased risk to develop a BSI compared with patients with chronic hepatitis, specifically for Gram-positive (and Staphylococcus spp)-related BSI.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions

IntroductionThe introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. AimWe evaluated the effect of food intake on LS in patients with different degrees of liver disease. Patients and methodsWe evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. ResultsFood intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. ConclusionLS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions.