Liver stiffness assessed by transient elastography in patients with β thalassaemia major

Rationale for the study. This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by β thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values.Materials and methods. The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearson’s rcoefficient was used to test correlations between liver stiffness measurements and all other variables.Results. In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls β thalassaemia major patients had a significant increase in LSMs independently from HCV infection.     

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals

IntroductionThe aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents.Patients and methodsThis cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness–spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed.ResultsNinety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p = 0.02), spleen stiffness measurement (39.4 vs 46.05; p = 0.04), liver stiffness–spleen diameter to platelet ratio score (1.21 vs 2.02; p = 0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p = 0.04) and variceal risk index (?3.4 vs ?1.02; p = 0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3 kPa for liver stiffness measurement and 27 kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance.DiscussionLiver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.     

Dietary supplementation in patients with alcoholic liver disease：a review on current evidence

BACKGROUND: Alcoholic liver disease (ALD) is one of the main causes of liver disease worldwide. Although the patho-genesis of ALD has not yet been well elucidated, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxy-gen species play a pivotal role in the clinical and pathological spectrum of the disease. This review summarizes the existing evidences on dietary supplements considered to have antioxi-dant, and/or anti-inlfammatory properties, and their role in the management of ALD and the proposed mechanisms.
DATA SOURCES: The present study reviewed all studies pub-lished in PubMed, ScienceDirect and Scopus, from 1959 to 2015, indicating the role of different dietary supplementation in attenuation of many pathophysiological processes involved in development and progression of ALD. Full-texts of citations were used except for those that were published in languages other than English.
RESULTS: Signiifcant progress has been made to understand the key events and molecular players for the onset and pro-gression of ALD from both experimental and clinical studies;however, there is no successful treatment currently available. The present review discussed the role of a variety of dietary supplements (e.g. vitamin A, carotenoids, vitamins B3, C and E, in addition to antioxidants and anti-inlfammatory agents) in treating ALD. It has been shown that supplementation with some carotenoids, vitamin B3, vitamin C, silymarin, curcumin, probiotics, zinc, S-adenosylmethionine and garlic may have potential beneifcial effects in animal models of ALD; however, the number of clinical studies is very limited. In addition, sup-plementation should be accompanied with alcohol cessation.
CONCLUSIONS: Since oxidative stress and inlfammation are involved in the pathogenesis of ALD, dietary supplements that can modulate these pathologies could be useful in the treat-ment of ALD. In addition to alcohol cessation, these supple-ments have shown beneifcial effects on animal models of ALD. Clinical trials are needed to validate the beneifciary role of these supplements in patients with ALD.     

High prevalence of metabolic complications in patients with non‐alcoholic fatty liver disease

Background: Non‐alcoholic fatty liver disease (NAFLD) is considered to be the liver component of the metabolic syndrome and is frequently associated with obesity, dyslipidemia and type II diabetes mellitus (NIDDM). We aimed to determine the development of liver function tests (LFTs) and metabolic complications in patients previously diagnosed with NAFLD. Methods: One‐hundred‐and‐two patients with NAFLD diagnosed in the period 1994–2001 were identified. Eighty were brought in for new investigations, including LFTs, blood pressure, BMI, lipid profile, blood glucose and insulin. Original liver biopsy was re‐evaluated. Results: Sixty‐two patients (77%) were males (median age 46 years; mean follow‐up time 2.8?±?1.2 years). Fifty‐four patients (68%) were light to moderately overweight with body mass index (BMI) 25–30?kg/m ² . Mean BMI (28.2) was the same at diagnosis and at follow‐up (28.3). At the new examination, 18 patients (23%) had developed diabetes mellitus type II (n?=?6) or had impaired fasting glucose (IFG) (n?=?12), compared to only 2 patients at diagnosis. Hyperinsulinemia was observed in 19 patients (24%). Dyslipidemia, with elevated triglycerides and/or hypercholesterolemia, was now present in 65 patients (81%). Twenty‐two patients (27%) had hypertension compared to 9 (11%) at diagnosis. Liver biopsy was performed in 24%, and 89% of those fulfilled the criteria for NASH. However, mild inflammation and fibrosis was observed, grade 1–2 (n?=?17), stage I–II (n?=?13) and none had cirrhosis. Conclusion: A significant proportion of patients with both clinical and histological diagnosis of NAFLD develop metabolic problems soon after diagnosis. These patients should be screened regularly for metabolic disorders.     

Screening for liver fibrosis by using FibroScan® and FibroTest in patients with diabetes

BackgroundPatients with diabetes are at risk for nonalcoholic fatty liver disease leading to cirrhosis. Existing guidelines do not advocate screening for liver related complications amongst persons with diabetes.AimThe aim of this prospective study was to identify patients with severe liver fibrosis amongst patients hospitalized for their diabetes, using non-invasive methods, and to evaluate factors associated with severe fibrosis.MethodsConsecutive patients with type 1 or 2 diabetes had clinical, biological parameters and liver fibrosis evaluation. Severe fibrosis was predicted when FibroTest was >0.59 or liver stiffness >8.7 kPa.ResultsA total of 277 patients were evaluated (type 1 diabetes 52%). The prevalence of severe fibrosis was 15.5%. By univariate analysis, factors associated with severe fibrosis were age, type 2 diabetes, body mass index, metabolic syndrome, previous cardiovascular events, no retinopathy, past history of foot ulcer, and elevated alanine aminotransferase. By multivariate analysis, factors associated with severe fibrosis were age >50 years, type 2 diabetes, no retinopathy, and past history of foot ulcer.ConclusionThis study showed an elevated prevalence of severe fibrosis in hospitalized diabetic patients, especially patients aged 50 years or older with type 2 diabetes, or with a past history of foot ulcer.     

Comments on “Effect of type 2 diabetes mellitus in the prognosis of acute-on-chronic liver failure patients in China”

A study addressing the influence of type 2 diabetes on the prognosis of acute-on-chronic liver failure patients was reviewed. Some statistical deficiencies were found in the reviewed article, and the sample size was too small to support the study. In addition, age should have been considered as one of the prognostic factors.     

Effect of Human Angiostatin® Protein on Human Angiogenesis in vitro

Angiostatin, a 38-kD fragment of plasminogen, inhibits angiogenesis in both animal tumor models and in vitro endothelial cell models. However, human Angiostatin has not been tested in vitro against an intact human tissue target to determine its ability to inhibit the initiation or subsequent promotion of the human angiogenic response. We hypothesized that high doses of human Angiostatin would inhibit the development of an angiogenic response in an intact human vessel target, and would suppress the subsequent growth of blood vessels following the initiation of an angiogenic response. To test these hypotheses, full-thickness human placental vein disks were cultured for 15 days in an in vitro fibrin-thrombin clot assay. This assay system had been used to evaluate the efficacy of a wide variety of compounds. Vessels were obtained from three placentas. Treatments included a control medium plus fetal bovine serum (FBS), heparin-steroid (300 micro g/ml heparin and 350 micro g/ml hydrocortisone; a treatment known to inhibit angiogenesis) and Angiostatin at doses from 1 x 10(-4) to 1 x 10(-9) M. In the control groups, 81% of vessels initiated an angiogenic response compared to 53% of the vessels treated with heparin-steroid. Angiostatin (10(-4)-10(-9) M) decreased the initiation of an angiogenic response, but this was not statistically significant. Of the disks that initiated an angiogenic response, the mean ( +/- standard error of the mean (SEM)) semi-quantitative visual angiogenic index (AI) of the control vessels was 9 +/- 1.7 on day 15. In comparison, the mean AI of heparin-steroid treated vessels was 3.7 +/- 0.4. Angiostatin at doses of 10(-4)-10(-9) M also failed to inhibit blood vessel growth after initiation of the angiogenic response. Based on these observations, we cannot demonstrate significant activity of human Angiostatin (10(-4)-10(-9) M) against the initiation or promotion of a human angiogenic response in this in vitro model of angiogenesis using an intact human vessel target.     

Effect of Prometheus liver assist system on systemic hemodynamics in patients with cirrhosis： A randomized controlled study

AIM： To evaluate treatment safety and hemodynamic changes during a single 6-h treatment with the PrometheusTM liver assist system in a randomized, controlled study. METHODS： Twenty-four patients were randomized to either the study group or to one of two control groups： Fractionated Plasma Separation Adsorption and Dialysis, PrometheusTM system （Study group; n = 8）; Molecular Adsorbent Recirculation System （MARS）TM （Control group 1, n = 8）; or hemodialysis （Control group 2; n = 8）. All patients included in the study had decompensated cirrhosis at the time of the inclusion into the study. Circulatory changes were monitored with a Swan-Ganz catheter and bilirubin and creatinine were monitored as measures of protein-bound and water-soluble toxins. RESULTS： Systemic hemodynamics did not differ between treatment and control groups apart from an increase in arterial pressure in the MARS group （P = 0.008）. No adverse effects were observed in any of the groups. Creatinine levels significantly decreased in the MARS group （P = 0.03） and hemodialysis group （P = 0.04）. Platelet count deceased in the Prometheus group （P = 0.04）.CONCLUSION： Extra-corporal liver support with Prometheus is proven to be safe in patients with endstage liver disease but does not exert the beneficial effects on arterial pressure as seen in the MARS group,     

Dynamic changes of capillarization and peri-sinusoid fibrosis in alcoholic liver diseases

AIM:To investigate the dynamic changes of capillarizationand ped-sinusoid fibrosis in an alcoholic liver disease modelinduced by a new method.METHODS:Male SD rats were randomly divided into 6groups,namely normal,4 d,2 w,4 w,9 w and 11 w groups.The animals were fed with a mixture of alcohol for designateddays and then decollated,and their livers were harvestedto examine the pathological changes of hepatocytes,hepaticstellate cells,sinusoidal endothelial cells,sinusoid,peri-sinusoid.The generation of three kinds of extra cellular matrixwas also observed.RESULTS:The injury of hepatocytes became severer asmodeling going on.Under electronic microscope,fattyvesicles and swollen mitochondria in hepatocytes,activatedhepatic stellate cells with fibrils could been seen near oraround it.Fenestrae of sinusoidal endothelial cells weredecreased or disappeared,sinusoidal basement was formed.Under light microscopy typical peri-sinusoid fibrosis,gridding-like fibrosis,broaden portal areas,hepatocyte's fatty andballoon denaturation,iron sediment,dot necrosis,congregated lymphatic cells and leukocytes were observed.Type Ⅰ collagen showed an increasing trend as modelinggoing on,slightly recovered when modeling stopped for 2weeks.Meanwhile,type Ⅳ collagen decreased rapidly whenmodeling began and recovered after modeling stopped for2 weeks.Laminin increased as soon as modeling began anddid not recover when modeling stopped for 2 weeks.CONCLUSION:The pathological changes of the modelwere similar to that of human ALD,but mild in degree.Ithad typical peri-sinusoid fibrosis,however,capillarizationseemed to be instable.It may be related with the reductionof type Ⅳ collagen in the basement of sinusoid duringmodeling.     

Is liver biopsy necessary in the management of alcoholic hepatitis?

Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.     

Risk factors for alcoholic liver disease in China

AIM:To examine the association of daily alcohol intake,types of alcoholic beverage consumed,drinking patternsand obesity with alcoholic liver disease in China.METHODS:By random cluster sampling and a 3-yearfollow-up study,1270 alcohol drinkers were recruited fromdifferent occupations in the urban and suburban areas ofXi'an City.They were examined by specialists and inquiredfor information on:Medical history and family medicalhistory,alcohol intake,types of alcoholic beverageconsumed,drinking patterns by detailed dietaryquestionnaires.Routine blood tests and ultrasonographywere done.RESULTS:Multivariate analysis showed that:(1) The riskthreshold for developing alcoholic liver disease wasingestion of more than 20 g alcohol per day,keeping ondrinking for over 5 years in men.The highest OR was atthe daily alcohol consumption≥160g,the occurrencerate of ALD amounted to 18.7% (P<0.01).No ALDoccurred when ingestion of alcohol was less than 20gper day.(2) 87.9% of all drank only at mealtimes.Thecumulative risk of developing ALD was significantly higherin those individuals who regularly drank alcohol withoutfood than in those who drank only at mealtimes,especiallyfor those who regularly drank hard liquors only andmultiple drinks (P<0.05).(3) The alcohol consumption inthose with BMI≥25 was lower than in those with BMI<25,but the risk increased to 11.5%,significantly higherthan that of general population,6.5% (P<0.01).(4)Abstinence and weight reduction could benefit the liverfunction recovery.CONCLUSION:In the Chinese population the ethanol riskthreshold for developing ALD is 20 g per day,and this riskincreases with increased daily intake.Drinking 20g ofethanol per day and for less than 5 years are safe fromALD.Drinking alcohol outside mealtimes and drinking hardliquors only and multiple different alcohol beverages bothincrease the risk of developing ALD.Obesity also increasesthe risk.Abstinence and weight reduction will directly affectthe prognosis of ALD.Doctor's strong advice might influencethe prognosis indirectly.     

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial

Abstract

Background. Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. Aim. To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. Methods. Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. Conclusions. (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.     

Assessment of prognosis in alcoholic liver disease: can serum hyaluronate replace liver biopsy?

1. Only 15-20% of chronic alcohol misusers ever develop cirrhosis. 2. Currently it is not possible to predict clinically who will develop progressive fibrotic alcoholic liver disease. 3. Liver biopsy is currently the gold standard diagnostic test in alcoholic liver disease, but it has associated morbidity and mortality. 4. Serum hyaluronic acid is a simple non-invasive test that may be able to give an estimate of the severity of fibrosis in alcoholic liver disease. The full clinical assessment of alcoholic liver disease includes liver biopsy, since accurate clinical prediction of the severity of liver damage is extremely difficult in all except very advanced cases. Unfortunately, liver biopsy has an associated complication rate and is contraindicated in, or unacceptable to, some patients. A reliable non-invasive test of the severity of fibrotic disease would be clinically useful at initial clinical assessment in some patients with alcoholic liver disease. Such a test would be more useful in subsequent monitoring of disease progression, and in particular may diminish the need for follow-up liver biopsy. Serum hyaluronic acid has been put forward as such a non-invasive test. Based on current evidence, serum hyaluronic acid may well be a useful adjunctive test in the assessment of certain categories of alcoholic liver disease patients, but at present it is unlikely to displace liver biopsy as the investigation of choice in alcoholic liver disease.