cirrhosis

摘要： BACKGROUND Liver cirrhosis and hepatocellular carcinoma(HCC)are highly prevalent in Australia’s Northern Territory.Contributing factors include high levels of alcohol consumption,viral hepatitis and metabolic syndrome.Rural Aboriginal residents form a significant proportion of the Central Australian population and present a challenge to traditional models of liver care.HCC surveillance and variceal screening are core components of liver cirrhosis management.AIM To assess participation in HCC and variceal surveillance programmes in a Central Australian liver cirrhosis patient cohort.METHODS Retrospective cohort study of patients with liver cirrhosis presenting to Alice Springs Hospital,Australia between January 1,2012 and December 31,2017.Demographic data,disease severity,attendance at hepatology clinics,participation in variceal and/or HCC surveillance programmes was recorded.Regression analyses were conducted to assess factors associated with two independent outcomes:Participation in HCC and variceal surveillance.RESULTS Of 193 patients were identified.82 patients(42.4%)were female.154 patients(80%)identified as Aboriginal.Median Model for End-stage Liver Disease Score at diagnosis was 11.Alcohol was the most common cause of cirrhosis.Aboriginal patients were younger than non-Aboriginal patients(48.4 years vs 59.9 years,P<0.001).There were similar rates of excess alcohol intake(72.6%vs 66.7%,P=0.468)and obesity(34.5%vs 38.4%,P=0.573 across non-Aboriginal and Aboriginal cohorts.20.1%of patients took part in HCC surveillance and 42.1%of patients completed variceal screening.Aboriginal patients were less likely to engage with either HCC surveillance(OR:0.38,95%CI:0.16-0.9,P=0.025)or undergo variceal screening(OR:0.31,95%CI:0.14-0.65,P=0.002).CONCLUSION HCC or variceal surveillance programmes had less uptake amongst Aboriginal patients.Greater emphasis needs to be placed on eliminating cultural obstacles to accessing hepatology services.

摘要： BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centric"therapies,such as the administration of nonabsorbable disaccharides,nonabsorbable antibiotics,probiotics and prebiotics.AIM To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle(EcN)1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.METHODS From January 2017 to March 2020,a total of 45 patients with HE were enrolled in this prospective,single-centre,open-label,randomized study.Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups:The EcN group(n=15),lactulose group(n=15)or rifaximin group(n=15)for a 1 mo intervention period.The main primary outcomes of the study were changes in serum ammonia and Stroop test score.The secondary outcomes were markers of a chronic systemic inflammatory response(ІL-6,ІL-8,and IFN-γ)and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.RESULTS Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group.However,the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E.coli with altered properties and pathogenic enterobacteria in patient faeces.In the primary outcome analysis,improvements in the Stroop test parameters in all intervention groups were observed.Moreover,EcN-treated patients performed 15%faster on the Stroop test than the lactulose group patients(P=0.017).Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ,IL-6 and IL-8.EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSION The use of the probiotic EcN strain was safe and quite efficient for HE treatment.The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines,normalized the gut microbiota composition and improved the cognitive function of patients with HE.The application of the EcN strain was more effective than lactulose treatment.

摘要： BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affecting glucose and lipid metabolism and the regulation of bile acid secretion as well as cell proliferation,differentiation,and motility.Additionally,FGF-19 secretion in an autocrine style has reportedly contributed to cancer progression in various types of malignancies including hepatocellular carcinoma(HCC).AIM To estimate the serum FGF-19 concentrations in HCC cases and assess its diagnostic performance for the detection of HCC.METHODS We recruited 90 adult participants and divided them into three equal groups:Healthy controls,cirrhosis patients,and HCC patients.Serum FGF-19 concentrations were measured using the Human FGF-19 ELISA kit.RESULTS We detected a high statistically significant difference in serum FGF-19 levels among the three groups.The highest level was observed in the HCC group,followed by the cirrhosis and control groups(236.44±40.94 vs 125.63±31.54 vs 69.60±20.90 pg/mL,respectively,P≤0.001).FGF-19 was positively correlated with alpha fetoprotein(AFP;r=0.383,P=0.003)and international normalised ratio(r=0.357,P=0.005),while it was negatively correlated with albumin(r=-0.500,P≤0.001).For the detection of HCC,receiver operating characteristic curve analysis showed that the best cut-off point of AFP was>8.2 ng/mL with an area under the curve(AUC)of 0.78,sensitivity of 63.33%,specificity of 83.33%,positive predictive value(PPV)of 79.2%,negative predictive value(NPV)of 69.4%,and total accuracy of 78%.However,FGF-19 at a cut-off point>180 pg/mL had an AUC of 0.98,sensitivity of 100%,specificity of 90.0%,PPV of 90.0%,NPV of 100%,and total accuracy of 98%.CONCLUSION FGF-19 represents a possible novel non-invasive marker for HCC.It may improve the prognosis of HCC patients due to its utility in several aspects of HCC detection and management.

摘要： BACKGROUND Von-Willebrand factor(vWF)disposes certain prognostic value in patients with liver cirrhosis,but its relation to other prognostic indicators has not been fully investigated.AIM To analyze the relation between vWF and other prognostic indicators in cirrhotic patients and to evaluate its prognostic value for mortality.METHODS This analytic prospective study was carried out in a tertiary center and initially enrolled 71 patients with liver cirrhosis and portal hypertension.It analyzed the relation between vWF and the stage of the disease and several inflammatory and prognostic indicators.The prospective analysis,performed on a sample of 63 patients,evaluated the association between the selected variables[vWF,Model for End-stage Liver Disease(MELD)score,C-reactive protein(CRP),ferritin,vitamin D,activated partial thromboplastin time,thrombin time,D-dimer concentration]and the survival time as well as their predictive value in terms of 3-mo,6-mo and 1-year mortality.RESULTS vWF was significantly higher in patients with higher Child-Turcotte-Pugh class(P=0.0045),MELD group(P=0.0057),ferritin group(P=0.0278),and D-dimer concentration(P=0.0232).vWF significantly correlated with D-dimer concentration,ferritin,CRP,International Normalized Ratio,and MELD,Child-Turcotte-Pugh,Sequential Organ Failure Assessment,and CLIF-consortium organ failure(CLIF-C OF)scores.vWF,MELD score,and CRP were significantly associated with death and were significant predictors of 3-mo,6-mo,and 1-year mortality.Each vWF unit significantly increased the probability for 3-mo mortality by 1.005 times(P=0.008),for 6-mo mortality by 1.006 times(P=0.005),and for 1-year mortality by 1.007 times(P=0.002).There was no significant difference between the diagnostic performance of vWF and MELD score and also between vWF and CRP regarding the 3-mo,6-mo,and 1-year mortality.CONCLUSION In patients with liver cirrhosis,vWF is significantly related to other prognostic indicators and is a significant predictor of 3-mo,6-mo,and 1-year mortality similar to MELD score and CRP.

摘要： BACKGROUND Acute kidney injury(AKI)in cirrhosis is important complication with poor outcomes.And infections are common cause for acute decompensation.Infections in cirrhosis lead to acute deterioration of hemodynamics leading to precipitation of AKI.AIM To study predictors of mortality in patients with infection-associated AKI in cirrhosis.METHODS This was a prospective,observational study conducted at Tertiary care centre from January 2018 till April 2019.Total 119 participants with cirrhosis of liver presenting with AKI were included into the study.AKI was defined as per international club of Ascites-AKI criteria 2015.Patients were grouped into infection AKI and non-infection AKI.Non-infection AKI included patients with diuretic induced AKI and pre-renal AKI.Logistic regression analysis was used to determine predictors of mortality at 28-d.RESULTS Out of 119 patients,alcohol(n=104)was most common etiology of cirrhosis.The infection AKI included 67(56%)patients and non-infection AKI(n=52)included pre-renal AKI in 36(30%)and diuretic-induced AKI in 16(14%)patients.Infection AKI had significantly higher bilirubin,higher international normalized ratio(INR),low serum sodium,higher total leukocyte count(TLC)and higher prevalence of hepatic encephalopathy(HE)as compared to non-infection AKI.Infection AKI had higher progression of AKI(19/67 vs 2/52;P=0.01)and 28-d mortality(38/67 vs 4/5;P≤0.01)as compared to non-infection AKI.At 28-d,non-survivors(n=42)had significantly higher bilirubin,higher INR,low serum sodium,higher TLC and higher prevalence of HE as compared to survivors(n=77).On subgroup analysis of Infection AKI group,on multivariate analysis,serum bilirubin as well as presence of HE were independent predictors of 28-d mortality.There was no significant difference of mortality at 90-d between two groups.CONCLUSION Infection AKI in cirrhosis has a dismal prognosis with higher 28-d mortality as compared to noninfection AKI.Serum bilirubin and presence of HE predict 28-d mortality in infection AKI.

摘要： BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.Atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(P30 ng/kg/min are the most effective.However,safety increases with infusion rates≤30 ng/kg/min.

摘要： Alpha-fetoprotein(AFP)is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma(HCC)in combination with ultrasound and other imaging modalities.Its utility is limited because of both low sensitivity and specificity,and discrepancies among the different methods of measurements.Moreover,its accuracy varies according to patient characteristics and the AFP cut-off values used.Combination of AFP with novel biomarkers such as AFP-L3,Golgi specific membrane protein(GP73)and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC.Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis.Hereditary and other non-hepatic disorders can also cause AFP elevation.

摘要： BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis(NASH), through to advanced fibrosis and cirrhosis. Many patients with NAFLD remain undiagnosed and recognizing those at risk is very crucial. Although liver biopsy is the gold standard method for diagnosing and staging NAFLD, non-invasive imaging and lab modalities are also very promising in diagnosing these diseases.AIM To explore some of these non-invasive modalities in this context and assess how they hold up in terms of making a diagnosis while avoiding an invasive procedure like a liver biopsy.METHODS This study was conducted on NAFLD/NASH patients(n = 73) who underwent Fibroscan examinations at Saint George Hospital University Medical Center over 17 mo in order to assess liver fibrosis. Obtained Fibroscan results were correlated to laboratory tests and calculated aspartate transaminase(AST)/alanine transaminase(ALT) ratio, AST platelet ratio index(APRI) score and Fibrosis-4 score.RESULTS A significant age difference was observed across fibrosis stages of investigated patients. The mean stiffness score was 9.48 ± 11.77 KPa. A significant negative correlation was observed between ALT, AST, Albumin, gamma-glutamyl transferase, cholesterol, LDL, HDL, triglycerides, and ALP when compared across fibrosis stages. On the other hand, a significant positive correlation was found between Bilirubin, PT INR, partial thromboplastin time, glucose, and Platelet count when compared across fibrosis stages, in addition to AST/ALT ratio, APRI, and Fib-4 scores.CONCLUSION This study showed that Ultrasound alone is not efficient in the assessment of advancement of liver disease. Furthermore, the high positive relation between AST/ALT ratio, APRI and Fib-4 scores with fibrosis stages in NAFLD patients suggests that they could be used clinically in combination with Fibroscan to predict significant fibrosis and cirrhosis and to avoid liver biopsy.

摘要： BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases.Fibrosis progression varies markedly in patients with hepatitis C virus(HCV).Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV.AIM To investigate changes in liver stiffness measured by transient elastography(TE)in a large,racially diverse cohort of United States patients with chronic hepatitis C(CHC).METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral(DAA)therapy and untreated patients.Patients had≥2 TE measurements and no prior DAA exposure.We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment,controlling for age,sex,race,diabetes,smoking status,human immunodeficiency virus status,baseline alanine aminotransferase,and baseline liver stiffness.Separate regression models analyzed the change in liver stiffness as measured by kPa,stratified by cirrhosis status.RESULTS Of 813 patients,419(52%)initiated DAA treatment.Baseline liver stiffness was 12 kPa in 127(16%).Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients,respectively.There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment(0.016 kPa/month;CI:-0.051,0.084)or in the untreated group(0.001 kPa/mo;CI:-0.090,0.092),controlling for covariates.A higher baseline kPa score was independently associated with decreased liver stiffness.CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.

摘要： Hepatocellular carcinoma(HCC)is a global health challenge.Due to the high prevalence in low-income countries,hepatitis B virus(HBV)and hepatitis C virus infections remain the main risk factors for HCC occurrence,despite the increasing frequencies of non-viral etiologies.In addition,hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection.The molecular processes underlying HCC development are complex and various,either independent from liver disease etiology or etiology-related.The reciprocal interlinkage among non-viral and viral risk factors,the damaged cellular microenvironment,the dysregulation of the immune system and the alteration of gutliver-axis are known to participate in liver cancer induction and progression.Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis.The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance,both through clinical-biochemical scores and periodic ultrasound assessment.This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.