Melanie Beaton

Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients

Failure of liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) and unreliable results occur in ≈5% and 15% of patients, respectively, mainly due to obesity. In this multicenter study, we evaluated the feasibility and performance of the novel FibroScan XL probe in 276 patients with chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease [NAFLD]) and a body mass index (BMI) ≥28 kg/m2. Patients underwent liver biopsy and TE with the standard M and XL probes. TE failure was defined as no valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing ≥F2 fibrosis and cirrhosis (F4) versus biopsy were examined using areas under receiver operating characteristic curves (AUROC). FibroScan failure was less frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with the XL probe were obtained in 61% of patients in whom the M probe was unreliable. Among 178 patients with ≥10 valid LSMs using both probes, liver stiffness was highly correlated between probes (ρ = 0.86; P < 0.0005); however, median liver stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The AUROC of the XL and M probes were similar for ≥F2 fibrosis (0.83 versus 0.86; P = 0.19) and cirrhosis (0.94 versus 0.91; P = 0.28). Conclusion: Compared with the M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM in obese patients. Although the probes have comparable accuracy, lower liver stiffness cutoffs will be necessary when the XL probe is used to noninvasively assess liver fibrosis. (HEPATOLOGY 2012)

Controlled Attenuation Parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography.

Accurate tools for the noninvasive detection of hepatic steatosis are needed. The Controlled Attenuation Parameter (CAP) specifically targets liver steatosis using a process based on transient elastography.

Discordance in fibrosis staging between liver biopsy and transient elastography using the FibroScan XL probe

BACKGROUND & AIMS The FibroScan XL probe facilitates liver stiffness measurement (LSM) by transient elastography (TE) in obese patients, yet factors affecting its accuracy have not been described. Our objectives were to examine the prevalence, risk factors, and causes of discordance between fibrosis estimated by the FibroScan XL probe and biopsy. METHODS Two hundred and ten patients with chronic liver disease (45% viral hepatitis, 55% nonalcoholic fatty liver disease (NAFLD) and a body mass index (BMI) ≥ 28 kg/m(2)) underwent liver biopsy and TE with the FibroScan XL probe. Predictors of discordance ≥ 2 fibrosis stages between measures, which occurred in 11% of patients (n=24), were identified by comparing patient, TE, and biopsy characteristics of discordant and non-discordant cases. RESULTS Fibrosis estimated by the FibroScan XL probe was greater than biopsy in 75% (18/24) of discordant cases. Although biopsy quality was not associated with discordance, discordant cases were less likely to have ≥ 10 valid shots (75% vs. 97%; p=0.001), a success rate ≥ 60% (67% vs. 95%; p <0.0005), and an interquartile range over median liver stiffness (IQR/M) <21% (37% vs. 57%; p=0.07) than non-discordant cases. However, only increased BMI (odds ratio [OR] 1.09 per kg/m(2); 95% confidence interval [CI] 1.01-1.18; p=0.04) was independently associated with discordance; liver stiffness was of borderline significance (OR 1.73 per log(10)-transformed value; 95% CI 0.95-3.18; p=0.08). Discordance was 4- to 5-fold more frequent among patients with severe obesity (BMI ≥ 40 kg/m(2): 32% vs. 8%) and liver stiffness above the median of 7.0 kPa (20% vs. 4%; both p <0.0005). CONCLUSIONS Discordance between liver fibrosis estimated by biopsy and TE using the FibroScan XL probe was infrequent in this obese population. Patients with severe obesity and elevated liver stiffness have the greatest risk of discordance.

Meta‐analysis: vasoactive medications for the management of acute variceal bleeds

Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood.

Phase II clinical trial of phlebotomy for non-alcoholic fatty liver disease

Elevated iron indices are described in non‐alcoholic fatty liver disease and iron reduction has been suggested as a potential therapy.

CYP3A Activity and Expression in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the Western world, given its association with obesity, type 2 diabetes, and dyslipidemia. Medications are widely used in NAFLD to manage comorbid conditions, and there is significant interest in developing new drug therapies to treat the disease. Despite this, little is known about the effects of NAFLD on drug metabolism. We examined the activity and expression of the major drug-metabolizing enzyme subfamily, CYP3A, in subjects with NAFLD as well as in mouse and cellular models. CYP3A activity was determined in healthy volunteers and subjects with biopsy-proven NAFLD by oral midazolam phenotyping and measurement of plasma 4β-hydroxycholesterol, an endogenous metabolic biomarker. CYP3A4 transcriptional activity, metabolic activity, and expression were also assessed in a mouse and cellular model of NAFLD. Subjects with nonalcoholic steatohepatitis (NASH) had 2.4-fold higher plasma midazolam levels compared with controls. Plasma 4β-hydroxycholesterol was 51% and 37% lower than controls in subjects with simple steatosis and NASH, respectively. Fibrosis was associated with 57% lower plasma 4β-hydroxycholesterol levels than controls. Furthermore, hepatic CYP3A4 mRNA expression in NASH was 69% lower than control livers. CYP3A4 gene luciferase activity in the livers of NAFLD mice was 38% lower than that of controls. Lipid-loaded Huh7 human hepatoma cells had a 38% reduction in CYP3A4 activity and 80% lower CYP3A4 mRNA expression compared with the control. CYP3A activity is reduced in human NAFLD in addition to mouse and in vitro cell models of the disease.

Current Treatment Options for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.

Validation of volumetric and single-slice MRI adipose analysis using a novel fully automated segmentation method

To validate a fully automated adipose segmentation method with magnetic resonance imaging (MRI) fat fraction abdominal imaging. We hypothesized that this method is suitable for segmentation of subcutaneous adipose tissue (SAT) and intra‐abdominal adipose tissue (IAAT) in a wide population range, easy to use, works with a variety of hardware setups, and is highly repeatable.

Prognostic Factors and Survival in Patients with Hereditary Hemochromatosis and Cirrhosis

OBJECTIVES The survival of treated, noncirrhotic patients with hereditary hemochromatosis is similar to that of the general population. Less is known about the outcome of cirrhotic hereditary hemochromatosis patients. The present study evaluated the survival of patients with hereditary hemochromatosis and cirrhosis. METHODS From an established hereditary hemochromatosis database, all cirrhotic patients diagnosed from January 1972 to August 2004 were identified. Factors associated with survival were determined using univariate and multivariate regression. Survival differences were assessed using the Kaplan-Meier life table method. RESULTS Ninety-five patients were identified. Sixty patients had genetic testing, 52 patients (87%) were C282Y homozygotes. Median follow-up was 9.2 years (range 0 to 30 years). Nineteen patients (20%) developed hepatocellular carcinoma, one of whom was still living following transplantation. Cumulative survival for all patients was 88% at one year, 69% at five years and 56% at 20 years. Factors associated with death on multivariate analysis included advanced Child-Pugh score and hepatocellular carcinoma. Patients with hepatocellular carcinoma were older at the time of diagnosis of cirrhosis (mean age 61 and 54.6 years, respectively; P=0.03). The mean age at the time of diagnosis of hepatocellular carcinoma was 70 years (range 48 to 79 years). No other differences were found between the groups. CONCLUSIONS Patients with hereditary hemochromatosis and cirrhosis are at significant risk of developing hepatocellular carcinoma. These patients are older when diagnosed with carcinoma and may have poorer survival following transplantation than patients with other causes of liver disease. Early diagnosis and treatment of hereditary hemochromatosis by preventing the development of cirrhosis may reduce the incidence of hepatocellular carcinoma in the future.

Management of non-alcoholic fatty liver disease in 2015

There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease.