Pavel Taimr

Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study

Given that little is known about the prevalence of, and factors associated with, liver fibrosis in the general population, we aimed to investigate this in a large, well‐characterized cohort by means of transient elastography (TE). This study was part of the Rotterdam Study, a population‐based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kilopascals (kPa) was used as a cutoff suggesting clinically relevant fibrosis. Of 3,041 participants (age, 66.0u2009±u20097.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.72‐3.36; Pu2009<u20090.001), alanine aminotransferase (ALT; OR, 1.24; 95% CI: 1.12‐1.38; Pu2009<u20090.001), smoking (OR, 1.77; 95% CI: 1.16‐2.70; Pu2009=u20090.008), spleen size (OR, 1.23; 95% CI: 1.09‐1.40; Pu2009=u20090.001), hepatitis B surface antigen, or anti–hepatitis C virus positivity (OR, 5.38; 95% CI: 1.60‐18.0; Pu2009=u20090.006), and combined presence of diabetes mellitus (DM) and steatosis (OR, 5.20; 95% CI: 3.01‐8.98; Pu2009<u20090.001 for combined presence) were associated with LSM ≥8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9‐3.6) in participants ages 50‐60 years to 9.9% (6.8‐14.5) in participants >80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability: 17.2% [12.5‐23.4]; this probability did not increase with age [Pu2009=u20090.8]). Conclusion: In this large population‐based study of older adults, LSM ≥8.0 kPa, suggestive of clinically relevant fibrosis, was present in 5.6% and was strongly associated with steatosis and DM. In the context of an aging population and an increased prevalence of DM and obesity, this study illustrates that liver fibrosis may become a more prominent public health issue in the near future. (Hepatology 2016;63:138–147)

Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: The Rotterdam study

BACKGROUND & AIMSnCoffee and tea have been proposed to limit the progression of liver fibrosis in established liver disease, but it is unknown if this is also true for subclinical fibrosis. We therefore aimed to evaluate whether coffee and tea consumption are associated with liver stiffness in the general population.nnnMETHODSnThe Rotterdam Study is an ongoing prospective population-based cohort. We included participants who underwent transient elastography, ultrasound and completed a food frequency questionnaire. Coffee and tea consumption were categorized into no, moderate (>0-3), or frequent (⩾3) intake (cups/day), and tea further into green, black and herbal tea (no/any). Significant fibrosis was defined as liver stiffness measurements (LSM) ⩾8.0kPa. We performed regression analyses relating coffee and tea intake with fibrosis, steatosis and log-transformed LSM and adjusted for energy, sugar and creamer intake, age, gender, BMI, steatosis/LSM, HOMA-IR, ALT, alcohol, smoking, soda, healthy diet index and physical activity.nnnRESULTSnWe included 2,424 participants (age 66.5±7.4; 43% male) of whom 5.2% had LSM ⩾8.0kPa and 34.6% steatosis. Proportion of LSM ⩾8.0kPa decreased with higher coffee consumption (7.8%, 6.9% and 4.1% for no, moderate and frequent respectively; Ptrend=0.006). This inverse association was confirmed in multivariable regression (ORmod 0.75, 95% CI 0.33-1.67; ORfreq 0.39, 95% CI 0.18-0.86; p=0.005). Amongst tea consumers, only herbal tea consumers (36.3%) had lower log-transformed LSM after adjustment (Beta-0.05, 95% CI-0.08;-0.02, p=0.001). Subtypes of tea were associated with steatosis in univariate but not multivariable analysis.nnnCONCLUSIONSnIn the general population, frequent coffee and herbal tea consumption were inversely related with liver stiffness but not steatosis. Longitudinal analyses, as well as studies validating and unravelling underlying mechanisms are needed.nnnLAY SUMMARYnThe Rotterdam Study is a large ongoing population study of suburban inhabitants of Rotterdam in whom data on liver stiffness, as proxy for liver fibrosis, presence of fatty liver on ultrasound and detailed information on coffee and tea consumption were obtained in 2,424 participants. The consumption of herbal tea and daily consumption of three or more cups of coffee was related to the presence of lower liver stiffness, independent of a great number of other lifestyle and environmental factors. Previous studies have found a protective effect of coffee on established liver disease and we now show for the first time that this effect is already measurable in the general population.

Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population: The Rotterdam Study.

BACKGROUND & AIMSnThe coagulation system is known to be involved in fibrogenesis in patients with liver disease. We investigated whether common genetic prothrombotic risk factors are associated with an increased risk of fibrosis in the general population.nnnMETHODSnThis investigation was part of the Rotterdam Study, an ongoing, population-based cohort study. Liver stiffness (LS) was measured using transient elastography (Fibroscan) and associated with single nucleotide polymorphisms determining blood group type and presence of the Factor V Leiden (FVL) mutation or prothrombin G20210A gene variant.nnnRESULTSnReliable LS measurements and genetic data were obtained from 1055 Caucasian participants. LS ⩾8.0 kPa, suggestive of clinically relevant fibrosis, was observed in 101 subjects (9.6%). Presence of FVL or prothrombin G20210A was independently associated with an increased risk of LS ⩾8.0 kPa (OR 2.09, 95%CI 1.07-4.07, p=0.03). Combination of blood group type non-O and the FVL mutation or prothrombin G20210A variant resulted in an even higher risk of LS ⩾8.0 kPa (OR 3.36, 95%CI 1.50-7.56, p=0.003). Presence of the FVL mutation or prothrombin G20210A variant in participants with blood group non-O was associated with a predicted probability of 14.3% (7.7-23.8) of LS ⩾8.0 kPa.nnnCONCLUSIONSnParticipants carrying the FVL mutation or prothrombin G20210A variant have an increased risk of clinically relevant liver fibrosis, which is even higher in blood group type non-O carriers. The fact that genetic prothrombotic risk factors are associated with an increased risk of liver fibrosis suggests that coagulation plays an important role in fibrogenesis in the general population.

Donor-transmitted metastasis of colorectal carcinoma in a transplanted liver

A 62‐year‐old man with alcoholic liver cirrhosis underwent liver transplantation. The transplantation went uneventful and the ultrasound imaging of the liver performed after transplantation did not show any abnormalities. Eighteen months later, an intra‐hepatic focal lesion was found on ultrasound. A contrast‐enhanced ultrasound revealed a lesion with a malignant pattern of contrast uptake. The histo‐pathological and subsequent molecular‐pathological analysis concluded a colorectal metastasis of donor origin. The donor had no history of malignancy but no complete autopsy had been performed which illustrates the importance of the meticulous donors` screening. Transplanted patients carry a high risk of developing malignancy in general but donor related‐tumors are very rare. The therapeutic considerations differ substantially between recipient‐ and donor‐related malignancies. Therefore, considering the possibility of donor‐related tumor by raising suspicion of malignant lesion with appropriate imaging and distinction from recipient‐related malignancy by molecular analysis are crucial for proper therapeutic decision.

A Model-Based Prediction of the Probability of Hepatocellular Adenoma and Focal Nodular Hyperplasia Based on Characteristics on Contrast-Enhanced Ultrasound

Contrast-enhanced ultrasound (CEUS) is an emerging imaging technique that is increasingly used to diagnose liver lesions. It is of the utmost importance to differentiate between the two most common solid focal liver lesions (i.e., hepatocellular adenoma [HCA] and focal nodular hyperplasia [FNH]), because their management and follow-up differ greatly. The main objective of this study was to determine how frequently the specific CEUS features of HCA and FNH are visible on CEUS and to define their predictive value for discrimination between HCA and FNH. We included 324 CEUS examinations performed on patients with FNH (nxa0=xa0181) or HCA (nxa0=xa0143). Patients with HCA and FNH significantly differed with respect to age and CEUS features of steatosis, echogenicity, homogeneity, the presence of a central scar, central artery, arterial enhancement pattern, necrosis or thrombus and enhancement in the late venous phase.

Multiple biopsy passes and the risk of complications of percutaneous liver biopsy.

Background and aim To minimize the sample variability of liver biopsy, the tissue length should be at least 25u2009mm. Consequently, more than one biopsy pass is needed with cutting biopsy needles. We aimed to investigate the risk factors of biopsy-related complication, including the number of biopsy passes. Methods All consecutive liver biopsies performed between 2005 and 2014 were included. Biopsies were ultrasound assisted and performed with cutting biopsy needles. A complication was an event where the patient visited a healthcare provider because of biopsy-related complaints. Complications followed by hospitalization 2 or more days or intervention were considered severe. Results In total, 1806 liver biopsies were analyzed. Overall, 102 (5.6%) complications were observed, of which 31 (1.7%) were severe. One (0.06%) patient died. Common complications were pain (n=75/102; 74%) and bleeding (n=34/102; 33%). Two biopsy passes were not associated with an increased risk of complications compared with one biopsy pass [odds ratio (OR): 1.59; 95% confidence interval (CI): 0.83–3.04; P=0.16], whereas three or more biopsy passes increased this risk compared with one (OR: 2.97; 95% CI: 1.38–6.42; P=0.005) or two biopsy passes (OR: 1.87; 95% CI: 1.10–3.19; P=0.021). The risk of severe complications was not influenced by the number of biopsy passes (P>0.24). Hepatic malignancy (OR: 3.21; 95% CI: 1.18–8.73; P=0.022) and international normalized ratio 1.4 or more (OR: 7.03; 95% CI: 2.74–18.08; P<0.001) were risk factors of severe complications. Conclusion Severe complication rate and mortality were low. Performing multiple biopsy passes was not associated with severe complications, whereas hepatic malignancy or elevated international normalized ratio were associated with an increased risk.

LIVER CONTRAST-ENHANCED ULTRASOUND IMPROVES DETECTION OF LIVER METASTASES IN PATIENTS WITH PANCREATIC OR PERIAMPULLARY CANCER

The aim of this study is to provide a diagnostic performance evaluation of contrast-enhanced ultrasonography (CEUS) in detecting liver metastases in patients with suspected of pancreatic or periampullary cancer. Computed tomography (CT) is often insufficient for detection of liver metastases, but their presence plays a crucial role in the choice of therapy. Eighty-nine patients with suspected pancreatic or periampullary cancer were included in this prospective study with retrospective analysis. Patients underwent an abdominal CT and CEUS. Fifteen patients had liver metastases. The CT sensitivity was 73.3% (11/15), the specificity 93.2% (69/74), the positive predictive value (PPV) 68.8% (11/16) and the negative predictive value (NPV) 94.6% (69/73). Based on CEUS, the sensitivity was 80% (12/15), specificity 98.6% (73/74), PPV 92.3% (12/13) and NPV 96.1% (73/76). CEUS improved characterization of liver lesions in patients with suspected pancreatic or periampullary cancer compared with CT. CEUS can better detect benign liver lesions and distinguish false-positive or indeterminate CT results.

Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study

Dear Editor,nnIncreasing evidence suggests that genetic factors play a role in the multifactorial aetiology of liver fibrosis. In their recent paper, Zhao et al 1 support this by describing the role of the Jnk1 gene in liver fibrogenesis. Previously, the role of other inflammatory-related genes in the development of liver fibrosis has been described in patients with chronic liver diseases. In patients with chronic hepatitis C, Nalpas et al 2 demonstrated a strong association between single nucleotide polymorphisms (SNP) in the interferon gamma receptor 2 ( IFNGR2 ) gene and progression of liver fibrosis. The role of interferon gamma in liver fibrogenesis has been reported before, but the precise mechanism of this effect has not yet been fully elucidated.3 ,4 Currently, it is not known whether the genetic variants in the IFNGR2 gene also influence liver fibrogenesis in individuals without liver disease. Therefore, we aimed to study the association between the IFNGR2 SNPs and liver fibrosis in the general population.nnFor this purpose, we assessed the extent of liver fibrosis non-invasively by measuring liver stiffness (LS) using transient elastography (TE) (Fibroscan, Echosens) in 1059 participants of the Rotterdam study. Genotyping in these, almost exclusively Caucasian (99.6%) participants was performed with the Infinium II HumanHap 550K Genotyping Bead-Chip V.3 (Illumina, San Diego, California, USA). The Rotterdam Study is a large, ongoing, prospective population-based cohort study in subjects aged ≥55u2005years in …

Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI

Aim To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA). Patients and methods Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2–9 HCA and at least 10 HCA. Results A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2–9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in patients with inflammatory HCA compared with steatotic HCA (31 vs. 26, respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%), whereas patients with inflammatory HCA were often diagnosed with multiple lesions (122/166, 73%). Conclusion Our series show a significantly higher BMI and frequency of inflammatory HCA in patients with multiple HCA compared with single HCA.

High-Frame-Rate Contrast-enhanced US Particle Image Velocimetry in the Abdominal Aorta: First Human Results

Purpose To study the feasibility of high-frame-rate (HFR) contrast material-enhanced (CE) ultrasound particle image velocimetry (PIV), or echo PIV, in the abdominal aorta. Materials and Methods Fifteen healthy participants (six men; median age, 23 years [age range, 18-34 years]; median body mass index, 20.3 kg/m2 [range, 17.3-24.9 kg/m2]) underwent HFR CE US. US microbubbles were injected at incremental doses (0.25, 0.5, 0.75, and 1.5 mL), with each dose followed by US measurement to determine the optimal dosage. Different US mechanical index values were evaluated (0.09, 0.06, 0.03, and 0.01) in a diverging wave acquisition scheme. PIV analysis was performed via pairwise cross-correlation of all captured images. Participants also underwent phase-contrast MRI. The echo PIV and phase-contrast MRI velocity profiles were compared via calculation of similarity index and relative difference in peak velocity. Results Visualization of the aortic bifurcation with HFR CE US was successful in all participants. Optimal echo PIV results were achieved with the lowest contrast agent dose of 0.25 mL in combination with the lowest mechanical indexes (0.01 or 0.03). Substantial bubble destruction occurred at higher mechanical indexes (≥0.06). Flow patterns were qualitatively similar in the echo PIV and MR images. The echo PIV and MRI velocity profiles showed good agreement (similarity index, 0.98 and 0.99; difference in peak velocity, 8.5% and 17.0% in temporal and spatial profiles, respectively). Conclusion Quantification of blood flow in the human abdominal aorta with US particle image velocimetry (echo PIV) is feasible. Use of echo PIV has potential in the clinical evaluation of aortic disease.