Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal.

The prevalence of the non-alcoholic fatty liver disease has reached major proportions, being estimated to affect one-quarter of the global population. The reference techniques, which include liver biopsy and the magnetic resonance imaging proton density fat fraction, have objective practical and financial limitations to their routine use in the detection and quantification of liver steatosis. Therefore, there has been a rising necessity for the development of new inexpensive, widely applicable and reliable non-invasive diagnostic tools. The controlled attenuation parameter has been considered the point-of-care technique for the assessment of liver steatosis for a long period of time. Recently, many ultrasound (US) system manufacturers have developed proprietary software solutions for the quantification of liver steatosis. Some of these methods have already been extensively tested with very good performance results reported, while others are still under evaluation. This manuscript reviews the currently available US-based methods for diagnosing and grading liver steatosis, including their classification and performance results, with an appraisal of the importance of this armamentarium in daily clinical practice.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Assessment of clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND AND AIMS: To evaluate two-dimensional shear wave elastography (2DSWE) in parallel with transient elastography (TE) for diagnosing clinically significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with chronic liver disease. PATIENTS AND METHODS: Consecutive patients with suspicion of compensated advanced chronic liver disease (cACLD) [liver stiffness measurement (LSM) ≥ 10 kPa by TE, or morphological signs suggestive of cACLD on imaging], with no history of liver decompensation, underwent hepatic venous pressure gradient (HVPG) measurement, transjugular liver biopsy and esophagogastroduodenoscopy, which served as the reference methods for diagnosing CSPH, cACLD and HRV. All patients underwent LSM and spleen stiffness measurements (SSM) by 2DSWE and TE. RESULTS: Seventy-six (76) patients were included (78% men, mean age 62 years, body mass index 28.3 kg/m2 , 36.8% alcoholic, 30.3% non-alcoholic fatty liver disease, 14.5% viral hepatitis). Of them, 80.3%, 69.7%, 52.6% and 22.4% had cACLD, cirrhosis, CSPH and HRV respectively. LSM performed better than SSM in diagnosing CSPH and HRV. For CSPH, AUROCs (0.926 vs. 0.866), optimal cut-offs (20.1 vs. 20.2 kPa) and sensitivity/specificity (80.5%/94.3% vs. 77.5% /86.1%) were comparable for 2DSWE and TE. Ruling-out of CSPH by 2DSWE (LSM at cut-off with ≥90% sensitivity (13.5 kPa) and platelets ≥ 150 x 109 /L) performed comparably to TE, with 1/24 cases falsely classified as negative. For HRV, AUROCs were similar (0.875 2DSWE, 0.851 TE) with similar optimal LSM cut-offs enabling 100% sensitivity and ruling-out HRV. CONCLUSION: Liver stiffness measurement by 2DSWE appears to perform equally well as TE for diagnosing CSPH and ruling-out HRV in compensated chronic liver disease.

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

[Assessment of liver disease severity in patients with chronic viral hepatitis]. / Procjena tezine ostecenja jetre u bolesnika s kronicnim virusnim hepatitisom.

The best indicator of the severity of liver damage and prognosis in chronic viral hepatitis is extension of liver fibrosis. Extension of liver fibrosis can be assessed by liver biopsy and non-invasive physical or biological methods. Biopsy is used to define ethiology, severity (stage of fibrosis) and prognosis of liver disease. These informations are also usefull when estimating the risk-benefit and deciding on the modalities of antiviral therapy. Serological tests and elastography may distinguish significant fibrosis (F > or = 2) from baseline fibrosis (AUROC 0.77-0.83 for serology and 0.84 for elastography) and cirrhosis from noncirrhotic stages (AUROC 0.77-0.86 for serology and 0.9-0.94 for elastography). Individual method of choice with best performance to distinguish cirrhosis from noncirrhotic stages of liver is elastography. Combination of serological tests and transient elastography has 93-95% accuracy to predict liver cirrhosis, and in case of concordant values of both tests biopsy could be avoided in 77-80% of patients. In case of discordant values or those in favour of intermediate stages of fibrosis liver biopsy should be performed because in these situations non-invasive tests are less reliable. According to several studies liver stiffness as assessed by transient elastography has high predictive value for the development of decompensated cirrhosis and portal hypertensive complications and may also discriminate the patients with respect to the predicted 5-year survival.

[Biochemical markers in assessment of severity and prognosis of acute pancreatitis]. / Biokemijski parametri u procjeni tezine i prognoze akutnog pankreatitisa.

The authors reveal and discuss the role of novel biochemical parameters in early diagnosis of acute pancreatitis and assessment of the severity of the disease. These biochemical parameters, beside routinely used amilase and lipase, might enable us to early identify those patients who are at risk of developing severe form of pancreatitis or complications. These parameters include trypsinogen activation peptide (TAP), C-reactive protein (CRP, tripsinogen-2, procalcitonin, phospholipase-A2 (PLA2), carboxypeptidase activation peptide (CAPAP) and interleukin-6 and 8 (IL-6, IL-8). Although these markers are still not incorporated in routine clinical practice, IL-6, IL-10, procalcitonin and trypsinogen activation peptide seem to have a good chance to be used as a new biochemical markers in assessment of severity and prognosis of acute pancreatitis.