Multinodular fatty change in the liver in three patients with chronic hepatic porphyria: Contribution of sonography to the diagnosis.

We present three cases of chronic hepatic porphyria (CHP) in alcoholic patients, in which grayscale ultrasound (US) revealed multiple echogenic masses in the liver, mimicking multinodular hepatocellular carcinoma on alcoholic liver injury. In all cases, contrast-enhanced US (CEUS) showed iso-enhancement of the mass lesions throughout all vascular phases. Additionally, two-dimensional shear wave elastography (2DSWE) (performed in two cases) revealed the mass to have almost the same SWE value as the surrounding parenchyma. When encountering alcoholic patients with multiple echogenic masses in the liver, CHP must be included in the differential diagnosis. CEUS and 2DSWE allow us to increase our diagnostic confidence of CHP.

Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study.

OBJECTIVE: Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). DESIGN: A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. RESULTS: Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. CONCLUSION: In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.

Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort. RESULTS: A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71-0.83 and AUC ≥S2 = 0.78; 0.72-0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4-6) for detoxification, CAP decreased by 32 ±â€¯47 dB/m (p <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obese patients with body mass index ≥30 kg/m2 had a significantly higher CAP, which did not decrease significantly during detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal. LAY SUMMARY: CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

Visualizing the Conversion Process of Alcohol-Induced Fatty Liver to Steatohepatitis in Vivo with a Fluorescent Nanoprobe.

Excess alcohol consumption and the associated development of alcoholic liver disease (ALD) are major public health challenges worldwide. Since patients with the severe stages of ALD no longer benefit from clinical therapies, early warning of ALD holds significant promise for increasing the cure rate of ALD. Herein, we develop a bicolor fluorescent nanoprobe for dynamically monitoring the conversion process of alcohol-induced fatty liver to steatohepatitis in vivo through simultaneous imaging of microRNA 155 and osteopontin mRNA, which are related to fatty liver and steatohepatitis, respectively. The fluorescence imaging results indicate that the nanoprobe can effectively differentiate alcohol-induced fatty liver and steatohepatitis. Moreover, the nanoprobe can monitor the transmutation process of alcohol-induced fatty liver to steatohepatitis and assess the remission effects of N-acetyl cysteine for alcohol-induced liver injury. We anticipate the developed nanoprobe and imaging method can provide new ways for early warning, treatments, and prognosis of ALD.

Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample.

BACKGROUND/OBJECTIVES: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. SUBJECTS/METHODS: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses. RESULTS: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. CONCLUSIONS: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.

Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan®) is a recent method for non-invasive assessment of steatosis. Its usefulness in clinical practice is unknown. We prospectively investigated the determinants of CAP failure and the relationships between CAP and clinical or biological parameters in a large cohort of consecutive patients. METHODS: All CAP examinations performed in adult patients with suspected chronic liver disease were included. CAP failure was defined as zero valid shot. The following factors were analyzed for their influence on CAP value and the relationships between CAP and clinico-biological parameters: age, gender, body mass index, waist circumference, hypertension, diabetes, metabolic syndrome, alcohol use, liver stiffness measurement, indication, and different biological parameters. RESULTS: CAP failure occurred in 7.7% of 5323 examinations. By multivariate analysis, factors independently associated with CAP measurement failure were female gender, BMI, and metabolic syndrome. By multivariate analysis, factors significantly associated with elevated CAP were BMI [25-30]kg/m(2), BMI >30kg/m(2), metabolic syndrome, alcohol >14 drink/week and liver stiffness >6kPa. CAP increased with the number of parameters of metabolic syndrome, BMI, waist circumference, the presence of diabetes or hypertension, and the cause of the disease. In the 440 patients with liver biopsy, for the diagnosis of steatosis >10%, steatosis >33%, and steatosis >66%, AUROCs of CAP were 0.79 (95% CI 0.74-0.84, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), respectively. CONCLUSIONS: CAP provides an immediate assessment of steatosis simultaneously with liver stiffness measurement. The strong association of CAP with the metabolic syndrome and alcohol use could be of interest for the follow-up of NAFLD or alcoholic patients.

Ultrasound evaluation and correlates of fatty liver disease: a population study in a Mediterranean area.

BACKGROUND: The aim of this study was to evaluate the distribution of fatty liver-nonalcoholic (NAFL) and alcoholic (AFL)-and its association with metabolic syndrome and its components in a population sample from a Mediterranean area. METHODS: A sample of 2974 subjects (1679 males, 1295 females, age range 30-89 years) was randomly drawn from the population of a town in southern Italy. The survey visit included a validated semiquantitative food frequency questionnaire, anthropometric measurements, a blood sample taken in the morning after overnight fasting, as well as abdominal ultrasound examination to evaluate liver fat with a standardized scoring system. The 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of the metabolic syndrome was adopted. RESULTS: In this Mediterranean population, where alcohol intake is mostly as wine with meals, NAFL is present in 36.8% of men and 25.7% of women and AFL in 13.8% of men and 5.5% of women. NAFL and AFL are associated with metabolic syndrome and its characteristics, body mass index (BMI), and visceral and subcutaneous fat (in AFL subjects, only in women) measured by ultrasound. Stratifying by BMI and controlling for confounders (age, height, smoking habit, and alcohol consumption), in overweight and obese subjects, liver and visceral fat are associated with the metabolic syndrome both in men and women and subcutaneous fat only in women. In normal weight subjects, only liver fat in men is associated with the metabolic syndrome. CONCLUSIONS: Fatty liver is highly prevalent in this Mediterranean population and is associated with metabolic syndrome in overweight and obese men and women as well as in men with normal BMI.

Nonalcoholic fatty liver disease: US-based acoustic radiation force impulse elastography.

PURPOSE: To investigate the clinical usefulness of ultrasonography-based acoustic radiation force impulse (ARFI) elastography (ie, ARFI sonoelastography) in patients with a diagnosis of nonalcoholic fatty liver disease (NAFLD) and compare ARFI sonoelastography results with transient sonoelastography and serum fibrosis marker test results. MATERIALS AND METHODS: Written informed consent was obtained from all subjects, and the local ethics committee approved the study. Fifty-four patients with a liver biopsy-confirmed diagnosis of NAFLD (mean age, 50.6 years +/- 13.7) were examined. All patients with NAFLD and healthy volunteers underwent ARFI sonoelastography, transient sonoelastography, and serum liver fibrosis marker testing (hyaluronic acids, type IV collagen 7 S domain). Ten healthy volunteers underwent ARFI sonoelastography. ARFI sonoelastography results were compared with liver biopsy findings, the reference standard. ARFI sonoelastography findings were compared with liver biopsy, transient sonoelastography, and serum fibrosis marker test results. Student t testing was used for univariate comparisons; Kruskal-Wallis testing, for assessments involving more than two independent groups; and areas under the receiver operating characteristic curve (A(z)), to assess the sensitivity and specificity of ARFI sonoelastography for detection of stage 3 and stage 4 fibrosis. RESULTS: Median velocities in the patients with NAFLD were 1.040 m/sec for those with stage 0 fibrosis, 1.120 m/sec for those with stage 1, 1.130 m/sec for those with stage 2, 1.780 m/sec for those with stage 3, and 2.180 m/sec for those with stage 4. The A(z) for the diagnosis of hepatic fibrosis stages 3 or higher was 0.973 (optimal cutoff value, 1.77 m/sec; sensitivity, 100%; specificity, 91%), while that for the diagnosis of stage 4 fibrosis was 0.976 (optimal cutoff value, 1.90 m/sec; sensitivity, 100%; specificity, 96%). Significant correlations between median velocity measured by using ARFI sonoelastography and the following parameters were observed: liver stiffness measured with transient sonoelastography (r = 0.75, P < .0001), serum level of hyaluronic acid(r = 0.459, P = .0009), and serum level of type IV collagen 7 S domain (r = 0.445, P = .0015). CONCLUSION: There is a significant positive correlation between median velocity measured by using ARFI sonoelastography and severity of liver fibrosis in patients with NAFLD. The results of ARFI sonoelastography were similar to those of transient sonoelastography.

Alcohol drinking may not be a major risk factor for fatty liver in Japanese undergoing a health checkup.

The question of whether alcohol drinking is a risk factor for fatty liver as shown by ultrasonography was investigated by both cross-sectional and longitudinal approaches in Japanese undergoing a health checkup. In this cross-sectional study, 32,438 males (49.0 +/- 11.9 years old) and 31,009 females (48.2 +/- 11.6 years old) receiving a health checkup from 2000 to 2005 were included. Longitudinally, 5,444 males (49.8 +/- 10.7 years old) and 4,980 females (50.4 +/- 9.3 years old) participating in both 2000 and 2005 were included. Multiple logistic regression analyses were performed for both sexes, adjusted for age, BMI, and smoking. The prevalence of fatty liver in non-, occasional, daily moderate, and daily heavy drinkers was 28.5, 27.5, 18.7, and 19.1% in men and 12.4, 7.7, 5.4, and 6.7% in women, respectively (inverse association, P < or = 0.05 for both). Occasional, daily moderate, and daily heavy drinking in men and occasional and daily moderate drinking in women were inversely associated with fatty liver in the cross-sectional study. Daily moderate and heavy drinking appeared protective in men in the longitudinal study. Alcohol drinking may not be a major risk for fatty liver in Japanese undergoing a health checkup.

[Sialadenosis in a patient with alcoholic fatty liver developing after heavy alcohol drinking].

Sialadenosis is a unique form of non-inflammatory, non-neoplastic bilateral salivary gland disorder characterized by recurrent painless swelling which usually occurs in parotid glands. Alcoholism is one of the main causes of sialadenosis along with diabetes, bulimia, and other idiopathic causes. The prognosis is verified according to the degree of liver function. We present a case of a 46 year-old man who had alcoholic fatty liver disease diagnosed as alcoholic sialadenosis based on clinical points of recurrent bilateral parotid swelling after heavy alcohol drinking, computed tomography, and fine-needle aspiration biopsy. After stopping alcohol drinking and treated with conservative treatment, he got improved without specific sequela.

Colloid scintigraphy in non-alcoholic steatohepatitis: a conventional diagnostic method for an emerging disease.

AIM: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by diffuse fatty infiltration and Kupffer cell dysfunction which contributes to its pathogenesis. Since the liver biopsy, which is considered the 'gold standard' in diagnosing NASH, has some limitations other imaging methods have been explored as alternatives. Colloid scintigraphy is a good method reflecting Kupffer cell activity and we found it worthwhile to evaluate this technique in NASH. We aimed to present the common scintigraphic features and their clinicopathologic correlations in NASH. METHODS: Twenty-two new patients (11 female, mean age 43.7+/-10.8) with biopsy-proven NASH underwent colloid liver scintigraphy. The dynamic, static and SPECT images were performed after intravenous injection of 185 MBq Tc tin colloid. Hepatic perfusion, blood pool clearance time, colloid shift to spleen and bone marrow were assessed and liver right/left lobe ratio was calculated. RESULTS: The values calculated on static and tomographic (SPECT) images showed good correlation. Liver right/left lobe ratio was altered in all patients. Blood pool clearance time was prolonged in seven (32%) but hepatic perfusion was normal in all patients. Colloid shift to the spleen was observed in 55% of patients using SPECT analysis. No correlation between scintigraphy parameters and histological or biochemical findings were observed. CONCLUSION: Altered liver right/left lobe ratio was the universal finding in all our NASH patients. Other common scintigraphic features of NASH include colloid shift to spleen and prolonged blood pool clearance time. Liver scintigraphy might be a promising non-invasive tool in the follow-up of NASH patients in therapeutic trials.

Intratumoral steatosis in focal nodular hyperplasia coinciding with diffuse hepatic steatosis: CT and MRI findings with histologic correlation.

Focal nodular hyperplasia (FNH) is a benign tumorlike condition that is thought to be a hyperplastic response to increased blood flow in an arterial malformation rather than a true neoplasm. Radiologically, FNH usually shows typical findings on unenhanced and enhanced computed tomography (CT) and magnetic resonance images (MRI), with atypical features being the exception rather than the rule. We report an unusual case of FNH with extensive fatty infiltration of the lesion illustrated on CT and MRI and proven by histopathology.

Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload.

BACKGROUND/AIMS: It has been suggested that dual-energy CT could differentiate irregular fatty liver from other hypodense lesions. We compared dual-energy CT to ultrasound scan and single-energy CT in the diagnosis and quantification of fatty liver, with special reference to iron overload. METHODS: Twenty-seven patients were included according to ultrasound: fatty liver (n=16) and normal liver (n=11). Single and dual-energy CT were performed. Attenuation measurements of hepatic lobes and control tissues were taken at 140 kV and 80 kV CT-guided liver biopsy was done in fatty liver patients, the degree of infiltration was estimated, and the histologic iron overload determined (iron overload, n=11; iron-free, n=5). RESULTS: The mean changes in attenuation for the right hepatic lobe were: normal liver: -0.8 (ns); iron overloaded fatty liver: 1.5 (ns); and iron-free fatty liver: 7.7 (p<0.0053). A spleen-liver attenuation differential threshold of 12H (140 kV, single-energy CT) and a right hepatic lobe 140 kV to 80 kV attenuation differential threshold of 9 H (dual-energy CT) were specific for fatty liver. Histology confirmed all cases of fatty liver diagnosed by ultrasound, independently of iron overload. Ultrasound did not differentiate cases of irregular from diffuse fatty liver detected on CT. Iron overload produced a masking effect in CT, decreasing its sensitivity: fatty liver was diagnosed in 67% of cases by single-energy CT and in 20% by dual-energy CT. Degree of fatty infiltration correlated with single-energy CT. CONCLUSIONS: Ultrasound diagnosed fatty liver best. Single-energy CT quantifies fatty infiltration, and best differentiates the irregular from the diffuse forms. Dual-energy CT is limited by poor sensitivity, especially in iron overload.

Usefulness of scintigraphy with Tc-99m phytate for the diagnosis of alcoholic foamy degeneration.

PURPOSE: Alcoholic foamy degeneration (AFD) is a liver disease causing temporary hepatocyte dysfunction. The prognosis is usually good, but liver biopsy is needed for diagnosis. We report the usefulness of liver-spleen scintigraphy with the radiocolloid Tc-99m phytate for the diagnosis of AFD. PATIENTS AND METHODS: We used liver scintigraphy with Tc-99m phytate to study three patients with AFD diagnosed on the basis of findings from a liver biopsy. RESULTS: Liver-spleen scintigraphy showed hepatomegaly and splenomegaly, and bone marrow was visible, but radioisotope uptake by the liver was uniform. CONCLUSIONS: This pattern of scintigraphic findings is different from that reported for patients with alcoholic fatty livers or severe alcoholic hepatitis, and seems to be specific for AFD.

Focal fatty infiltration of the liver associated with important mass effect.

A case of focal fatty infiltration of the liver (FFIL) with partly multinodular appearance and significant mass effect on computed tomography (CT) is presented. Mass effect in FFIL is sometimes seen with alcoholic liver disease and makes the differential diagnosis with malignant disease often difficult. Diagnosis of FFIL was confirmed on 1.5 T MR images.

New method of estimating the ultrasonic beam ratio parameter for characterizing sound propagation in tissue.

The backscattered ultrasonic signal from soft tissue can be considered to consist of two parts: a spatially fluctuating component due to coherent scattering from randomly distributed scattering centers and a relatively constant component related to structural ordering. The relationship between these, which has been termed the "beam ratio parameter" influences the speckle pattern of an ultrasound image. First-order image statistics for this special speckle pattern are characterized by the Rician distribution. Changes of second-order statistics have also been derived as a function of the beam ratio parameter. A new method for the estimation of the beam ratio parameter from the intensity distribution of the ultrasonic signal is described in this paper. This method was used to measure the parameter in ultrasonic images from phantoms and liver tissue yielding values of about 0.1. The measured changes of the second-order statistics were not correlated to this parameter. The results indicate that the relatively constant intensity component related to structural ordering has only a small influence on the speckle pattern.

Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis.

The aim of the present study was to evaluate the effectiveness of single-energy computed tomography in determining iron overload in idiopathic hemochromatosis, with special reference to slightly overloaded cases. Liver attenuation was determined in 100 patients (46 cases of idiopathic hemochromatosis, 32 cases of chronic liver disease, and 22 normal controls). The iron load was determined for the first two groups by biochemical determination of liver iron concentration (performed in all but 12 subjects in the chronic liver disease group) and hepatic histologic grading. The main results for liver attenuation (upper normal limit, 72 Hounsfield units) showed that despite a high specificity (0.96), this parameter was of low sensitivity (0.63). Although mean liver attenuation in idiopathic hemochromatosis (77 +/- 14) was significantly higher than in chronic liver diseases (53 +/- 17; p less than 10(-4) and normal controls (66 +/- 3; p less than 10(-3], and despite an overall good correlation between liver attenuation and liver iron concentration (r = 0.72; p less than 10(-3], liver attenuation was unable to detect moderate iron overload. Fourteen of 18 patients with a liver iron concentration of less than 150 mumol/g dry liver wt had liver attenuation values of less than 72. Moreover, 3 of 18 subjects with a liver iron concentration of greater than 150 had a liver attenuation of less than 72. Of these 17 false-negatives, only 7 could be attributed to associated steatosis. On the whole, single-energy computed tomography, when used on a routine basis for diagnosing iron overload, is of limited clinical value in idiopathic hemochromatosis due to its poor sensitivity. Hepatic histologic examination together with biochemical determination remains the most accurate means to assess liver iron.