Steatosis Area Research Articles

Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 tesla MRI

To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non-alcoholic steatohepatitis using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male C57BL/6 mice were divided into control (n = 3) and experimental groups (n = 14) fed a methionine-deficient choline-deficient (MCD) diet to induce steatohepatitis. Livers underwent ex vivo diffusion-weighted MR imaging and ADC maps were calculated. A pathologist determined subjective scores of steatosis, classified from 0 to 3. Digital image analysis was used to determine percentage areas of steatosis. Graphs comparing ADC to subjective and digital image analysis (DIA) determinations of steatosis were plotted. Subjective assessments of steatosis ranged up to values of 3 and DIA determined areas of steatosis to range up to approximately 16%. ADC values approximated 800 × 10(-6) mm(2) /s (range, 749-811 × 10(-6) mm(2) /s, mean 786 × 10(-6) mm(2) /s) in controls and 500 × 10(-6) mm(2) /s (range, 478-733 × 10(-6) mm(2) /s, mean 625 × 10(-6) mm(2) /s) in experimental mice. Moderate correlation between ADC and subjective scores of steatosis (R = -0.56) was observed. Strong correlation between ADC values and percentage areas of steatosis was between ADC values and percentage areas of steatosis was observed greater (R = -0.81) and very strong correlation was observed with the exclusion of a single outlying data point (R = -0.91). Based on the comparison of ADC values and steatosis determinations by DIA, increasing degrees of steatosis are seen to result in decreased hepatic ADC values.

Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C

Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients. A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3 ± 10.8 years; 95 females, mean age 56.6 ± 10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy. Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development. Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.

Separate and combined effects of cyclic fasting and l-carnitine supplementation in red porgy (Pagrus pagrus, L. 1758)

We examined the effects of cyclic fasting in red porgy (Pagrus pagrus) fed different dietary carnitine levels. Juvenile fish (23.58 ± 3.49 g) were divided into eight groups – four groups were fed every day to apparent satiation, while the other four were fasted for 7 days every 2 weeks. In each feeding regime, two replicates were fed an l-carnitine non-supplemented diet (46 mg kg−1) and the other two groups were fed an l-carnitine supplemented diet (630 mg kg−1). Fish fed 630 mg l-carnitine accumulated two times more l-carnitine in muscle than fish fed 46 mg l-carnitine. Cyclic fasting reduced the growth performance and lipid content in the liver. Carnitine supplementation did not affect performance and body composition, but decreased the n-6 PUFA content. Moreover, the combined effects of fasting and carnitine supplementation were observed on reducing the n-3 fatty acid content. Areas of steatosis were found in the livers of red porgy, but the results revealed that supplementation of l-carnitine in cyclic fasted fish contributed towards a lower degree of vacuolization than in fish fed to apparent satiation. Regardless of the feeding regime applied, the spleen of fish fed the l-carnitine-supplemented diet was haemorrhagic and hyper activation of melanomacrophage cells was observed.

Noninvasive liver steatosis quantification using MRI techniques combined with blood markers

To evaluate the accuracy of different techniques of MRI steatosis quantification, based on histological grading and quantification of liver steatosis. Twenty-three patients (21 with nonalcoholic fatty liver disease and two controls) were included. Steatosis was evaluated in liver specimens using histological grading (five grades) and steatosis area (% of liver surface) was computed using an inhouse automated image analysis. The following five MRI quantification techniques were performed: two-point Dixon, three-point Dixon, DUAL, spin echo method and a new technique called multi-echo gradient-echo (MFGRE). Interobserver (two observers) and intersite (three different liver sites) agreements were evaluated for the two best-performing methods. Steatosis area was correlated with steatosis grade: Rs (Spearman coefficient) = 0.82, P value of less than 0.001. The steatosis area was significantly different between S0-S2 and S3-S4 grades: 4.2 + or - 2.4 versus 16.4 + or - 8.9% (P< 0.001). Correlations between the MRI techniques and steatosis area (or grading) were: MFGRE, Rs = 0.72 (0.78); spin echo method, Rs = 0.72 (0.76); DUAL, Rs =0.71 (0.76); two-point Dixon, Rs = 0.71 (0.75); three-point Dixon, Rs = 0.67 (0.77). Interobserver (Ric = 0.99) and intersite (Ric = 0.97) agreements were excellent for the liver steatosis measurement by MFGRE. The noninvasive diagnosis of the steatosis area was improved by adding blood markers like ALT and triglycerides to MFGRE (aR2: 0.805). MRI, and in particular the MFGRE method, provides accurate and automatic quantification for the noninvasive evaluation of liver steatosis, either as a single measurement or in combination with blood variables.

Indeterminate, Subcentimetric Focal Liver Lesions in Cancer Patients: Additional Role of Contrast-Enhanced Ultrasound

To evaluate whether the use of contrast-enhanced ultrasound (CEUS) could improve the characterization of indeterminate subcentimetric focal liver lesions (FLLs) seen with multidetector computed tomography (MDCT) in cancer patients. For 12 months all patients with extrahepatic tumors showing small (< 10 mm), indeterminate focal liver lesions on whole-body or abdominal computed tomography (CT) underwent immediate, targeted ultrasound (US) to rule out a cystic lesion. Whenever unenhanced US demonstrated a non-cystic lesion or failed to recognize any focal abnormality within the suspected area, CEUS was carried out. During the arterial phase, CEUS was focused on the area reflecting the CT finding, while the entire organ was explored during the portal-sinusoidal phase. Among the 132 patients with MDCT evidence of indeterminate, subcentimetric focal liver lesions (206 lesions), US proved the cystic nature of 138 lesions in 87 patients. In 45 cases US failed to recognize any abnormality or cystic image and these subjects underwent CEUS. The CEUS results were confirmed by further assessment or follow-up for 43 / 45 patients (3 cysts, 8 hemangiomas, 47 metastases, 2 areas of focal steatosis, 2 eosinophilic necroses, 1 granuloma, 1 abscess, 1 fistula). CEUS failed to detect 3 lesions (1 metastasis and 2 benign lesions). In 8 cases CEUS recognized additional liver metastases. CEUS can be helpful in demonstrating or excluding metastases in cancer patients with MDCT evidence of subcentimetric, indeterminate focal liver lesions.

A comparison of the fibrotic potential of nonalcoholic fatty liver disease and chronic hepatitis C

In nonalcoholic fatty liver disease the amount of fibrosis for individual histologic stages is unknown. To better understand the fibrotic potential of nonalcoholic fatty liver disease, we compared the amount of fibrosis in nonalcoholic fatty liver disease versus chronic hepatitis C virus patients. The area of fibrosis for equivalent fibrosis stages was measured by micromorphometry in 70 nonalcoholic fatty liver disease and 70 matched, untreated, chronic hepatitis C virus controls. The area of fibrosis correlated with Brunt stage (r = 0.71; P < .001) in nonalcoholic fatty liver disease and METAVIR stage (r = 0.58; P < .001) in chronic hepatitis C virus. Mean area of fibrosis was similar in nonalcoholic fatty liver disease and chronic hepatitis C virus patients (7.77% versus 7.70%). Although chronic hepatitis C virus patients displayed higher area of fibrosis in early disease (no or mild fibrosis), nonalcoholic fatty liver disease and chronic hepatitis C virus patients had similar area of fibrosis in more advanced disease (7.83% versus 8.06%, respectively; P = .86 for bridging fibrosis; and 16.62% versus 12.98%, respectively; P = .29 for cirrhosis). The area of fibrosis was similar in Brunt stage 3 nonalcoholic fatty liver disease and METAVIR stage 2 chronic hepatitis C virus, the usual threshold for initiating therapy. The area of steatosis declined with increasing fibrosis stages confirming the early loss of liver fat with progressive fibrosis in nonalcoholic fatty liver disease. Fibrosis is as abundant in nonalcoholic fatty liver disease as in chronic hepatitis C virus, especially in the advanced stages of the disease. The fibrotic potential of nonalcoholic fatty liver disease is as severe as that of chronic hepatitis C virus.

334 NON-INVASIVE DIAGNOSIS OF LIVER LESIONS BY BLOOD TESTS IN NAFLD

Background and Aims: Non invasive tests are not well developedin NAFLD. This could be partly due to the pathological description of certain lesions that is hampered by semi-quantitative scorings. Our aim was to develop an accurate non-invasive measurement of main liver lesions in NAFLD by blood tests based on a thorough pathological and morphometric analysis. Methods: Steatosis, NASH and fibrosis were graded according to CRN-NASH (Kleiner, Hepatology 2005) and Metavir systems in 226 patients with NAFLD. A fully automated, in-house software measured the fractal dimension (reflecting architecture) and the area (reflecting amount) of steatosis or fibrosis on liver specimens. Independent predictors were selected by logistic or multiple regression repeated in 1000 random bootstrap samples. When models were determined, a second bootstrap resampling was performed to measure optimism bias (Steyerberg et al. 2001).

The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice

Pro-inflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, are known to be involved in the establishment of insulin resistance. Insulin resistance plays a key role in the development of obesity-related pathologies, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The state of chronic inflammation associated with obesity led us to hypothesize that TNF-alpha blockade may have an effect on experimentally obese animals. We studied the effects of thalidomide, an immunosuppressant and anti-TNF-alpha drug, on hepatic alterations that were induced by a high-fat diet (HFD) in mice. Obesity was induced in Swiss mice using a HFD for 12 weeks. Thalidomide-treated animals received thalidomide i.p. (100 mg/kg/day, 10 days). Glucose, aspartate aminotransferases and alanine aminotransferases levels were assessed in the blood. Insulin and glucose tolerance tests were performed. The liver was excised for histological, triglyceride, gene and protein expression analyses. We found improvements in both the basal glucose blood levels and the response to insulin administration in the treated animals. The molecular analysis of insulin signalling revealed a restoration of the hepatic insulin receptor substrate (IRS)-1 and AKT phosphorylation. The hepatic expression of TNF-alpha was inhibited and the levels correlated with a significant reduction in the steatosis area. Other hepatic inflammatory markers, such as iNOS and suppressor of cytokine signalling (SOCS-3), were also reduced. We suggest that immunosuppressant drugs that target TNF-alpha and that may also contribute to reductions in the inflammatory markers that are associated with obesity could be a therapeutic option in NAFLD and type 2 diabetes.

Histologic Graft Assessment After Clinical Islet Transplantation

An accurate monitoring would help understanding the fate of islet grafts after transplantation. This work assessed the feasibility of needle biopsy monitoring after intraportal islet transplantation (n=16), and islet graft morphology was studied with the addition of autopsy samples (n=2). Pancreas autopsy samples from two nondiabetic individuals were used as control. Islet tissue was found in five needle samples (31%). Sampling success was related to size (100% sampling for the four biopsies of 1.8 cm in length or higher, P<or=0.01). Mild liver abnormalities included localized steatosis (n=8), mild nodular regenerative hyperplasia and mild portal venopathy (n=3), and hepatocyte swelling (n=2). Endocrine cell composition and distribution were similar between islet grafts and normal islets within the native pancreas. There was no or minimal immune cell infiltrate in patients on and off exogenous insulin, including two patients with ongoing negative metabolic events (increasing HbA1c or insulin requirement). The infiltrate was mainly composed of CD4- and CD8-positive cells. This study demonstrates that needle biopsy is feasible after clinical islet transplantation but with a limited practical value because of its low islet sampling rate using current sampling and analysis methods. Both biopsy and autopsy samples demonstrated the well-preserved islet endocrine composition after transplantation and the presence of focal areas of steatosis. Islet grafts showed no or minimal immune cell infiltration, even in the case of ongoing islet loss. On the basis of the findings, possible reasons for allograft islet loss are discussed.

Contrast‐enhanced ultrasound with SonoVue: Differentiation between benign and malignant focal liver lesions in 317 patients

The aim of the study was to investigate the ability of contrast-enhanced sonography (CEUS) with the contrast agent SonoVue to differentiate between benign and malignant focal liver lesions. In a prospective study, we examined 317 patients (204 males, 113 females, aged 59 +/- 12 years) with focal liver lesions detected by B-mode gray-scale sonography. After intravenous injection of 1.2 mL SonoVue, the liver was examined continuously for 3 minutes using low-MI sonography with contrast-specific software. Final diagnosis was established by histopathology, CT, MRI, or HIDA-scintigraphy. Two hundred nine patients had malignant focal lesions, including 107 hepatocellular carcinomas, 70 metastases, 26 cholangiocellular carcinomas, and 6 other types of malignancy. One hundred eight patients had benign focal lesions, including 30 regenerative nodules, 30 hemangiomas, 13 cases of focal nodular hyperplasia, 12 abscesses, 8 cases of necrosis, 7 cases of focal steatosis areas, and 8 other benign lesions. Hypoenhancement or no enhancement in the late phase was found in 91% of the malignant lesions but in only 37% of the benign lesions (p < 0.001, sensitivity = 64%, specificity = 93%). Hyperenhancement in the late phase was found in 20% of the benign lesions but in none of the malignant lesions (p < 0.001, sensitivity = 21%, specificity = 100%). Hyperenhancement in the early phase with diffuse complete enhancement was found in 30% of the patients with malignant lesions but in only 2% of the patients with benign lesions (p < 0.001, sensitivity = 30%, specificity = 98%). CEUS had a sensitivity of 90%, a specificity of 99%, and an accuracy of 89% in the diagnosis of malignant liver lesions. CEUS is helpful in the differentiation between benign and malignant focal liver lesions.

In Situ Lipidomic Analysis of Nonalcoholic Fatty Liver by Cluster TOF-SIMS Imaging

Mass spectrometry imaging has been used to map liver biopsies of several patients suffering from nonalcoholic fatty liver disease. This steatosis is characterized by an accumulation of triacylglycerols and diacylglycerols in the liver. Using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) with a bismuth cluster ion source, it has been possible to map lipids in situ at the micrometer scale and to simultaneously characterize their molecular distribution on liver sections. Accumulation of triacylglycerols, diacylglycerols, monoacylglycerols, fatty acids, with the apparition of myristic acid, together with a dramatic depletion of vitamin E and a selective macrovacuolar localization of cholesterol are observed in steatosis areas of fatty livers compared to control livers. These ion species are concentrated in small vesicles having a size of a few micrometers. Moreover, very fine differences in lipid localizations, depending on alkyl acid chain lengths of diacylglycerols and fatty acids, have been found after careful scrutiny of the ion images. Finally, TOF-SIMS has revealed lipid zonation in the normal human liver and accumulation of very similar lipids to those detected in areas of the fatty livers, which are not characterized as steatotic ones by the histological control performed on serial tissue sections.

Assessment of hepatic steatosis: comparison of quantitative and semiquantitative methods in 108 liver biopsies

There is growing interest in the role of hepatic steatosis in liver injury. The current standard for steatosis assessment is histological grading, although there is variability in the scoring systems used. The aim of this study was to compare steatosis assessment by image analysis and histological grading. Three methods were used to measure steatosis: histological grading (from 0 to 4); estimation of the percentage of hepatocytes (to nearest 5%) with steatosis; and computer-assisted image analysis. Image analysis was performed on multiple fields for each biopsy with image pro plus 4.5, with steatotic droplets identified on the basis of shape, colour and size. Computer-selected objects were reviewed to ensure that these were steatotic droplets. The predictive accuracy of the three techniques was assessed using measures of obesity and insulin resistance (homeostasis model assessment) as the outcome variables. There was a strong correlation between the results of image analysis and histological grade (r(s)=0.89, P<0.01), and estimated per cent steatosis (r(s)=0.93, P<0.01). The variability in the area of steatosis calculated by image analysis in different fields of a biopsy correlated with the total steatosis area (r(s)=0.93, P<0.01). Image analysis did not offer any additional predictive value when the association between degree of obesity or insulin resistance was correlated with the different methods of assessing steatosis. Image analysis allows measurement of area of steatosis in liver biopsy material and generates a continuous variable that facilitates statistical analysis. These aspects may prove beneficial in research settings.

Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice

As 5-lipoxygenase (5-LO) is an emerging target in obesity and insulin resistance, we have investigated whether this arachidonate pathway is also implicated in the progression of obesity-related fatty liver disease. Our results show that 5-LO activity and 5-LO-derived product levels are significantly elevated in the liver of obese ob/ob mice with respect to wild-type controls. Treatment of ob/ob mice with a selective 5-LO inhibitor exerted a remarkable protection from hepatic steatosis as revealed by decreased oil red-O staining and reduced hepatic triglyceride (TG) concentrations. In addition, 5-LO inhibition in ob/ob mice downregulated genes involved in hepatic fatty acid uptake (i.e., L-FABP and FAT/CD36) and normalized peroxisome proliferator-activated receptor alpha (PPARalpha) and acyl-CoA oxidase expression, whereas the expression of lipogenic genes [i.e., fatty acid synthase (FASN) and SREBP-1c] remained unaltered. Furthermore, 5-LO inhibition restored hepatic microsomal TG transfer protein (MTP) activity in parallel with a stimulation of hepatic VLDL-TG and apoB secretion in ob/ob mice. Consistent with these findings, 5-LO products directly inhibited MTP activity and triggered cytosolic TG accumulation in CC-1 cells, a murine hepatocyte cell line. Taken together, these findings identify a novel steatogenic role for 5-LO in the liver through mechanisms involving the regulation of hepatic MTP activity and VLDL-TG and apoB secretion.

Protective Effect of ACTIValoe N-931 Complex, a Mixture of Aloe vera and Silybum marianum, on Experimental Acute Liver Injury

The aim of this study was to investigate the hepatoprotective effect of <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute liver injuries. Acute liver damages were induced by intraperitoneal injection of galactosamine (GalN, 700 mg/kg), naphthylisothiocyanate (ANIT, 40 mg/kg) and ethionine (500 mg/kg). <TEX>$ACTIValoe^{(R)}$</TEX> N-931 (85, 170 and 340) was administered orally 48 h, 24 h, 2 h before and 6 h after the injection of hepatotoxins. At 24 h after GalN treatment the levels of serum aminotransferases and hepatic lipid peroxidation were significantly elevated, whereas hepatic glutathione, serum triglyceride (TG) and total cholesterol were decreased. These changes were attenuated by <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex. The serum aminotransferase activities and total bilirubin significantly increased at 48 h after ANIT treatment, but were attenuated by <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex. The bile flow was lower after ANIT treatment, which was restored by <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex. <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex reduced the ethionine-induced elevated hepatic TG contents. Histopathological analysis revealed that signs of liver injury were prominent at 24 h as result of ethionine injection, demonstrated by extensive areas of fatty change and microvesicular steatosis were observed around cells. These changes were attenuated by <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex. Our results suggest that the <TEX>$ACTIValoe^{(R)}$</TEX> N-931 complex has a protective effect on acute liver injury.

Predicting the viability of liver allografts procured from non-heart-beating donors: The role of histopathology

Predicting the viability of liver allografts procured from non-heart-beating donors: The role of histopathology

Relationships of Hepatic Histology to Metabolic, Inflammatory and Viral Parameters in Chronic HCV Infection

Purpose: Hepatic steatosis is commonly associated with chronic hepatitis C infection (HCV). The purpose of this study was to determine the associations between hepatic histology, and metabolic, inflammatory and viral parameters. Methods: This was a cross-sectional study of 31 hepatitis C infected subjects prior to HCV treatment, 21 male and 10 female, of whom 21 were HCV/HIV co-infected and 9 were HCV mono-infected. The infection was genotype I in 22 cases. Serum HCV RNA, soluble TNF receptors I and II (sTNFRI, II), fasting triglycerides, HDL-cholesterol, glucose and insulin levels were measured. Insulin resistance (IR) was calculated by HOMA. Body composition measures included BMI, body fat and fat free mass by bio-impedance analysis (BIA), and anthropometric measures of fat distribution. Liver biopsies were evaluated using a 4-point scale for disease activity (grade), and a 6-point scale for fibrosis (stage). Steatosis was measured using NIDDK 4-point scale plus a quantitative percent area estimate of macro and microvesicular fat. Data was analyzed by the general linear model method and by multiple regression, using steatosis, steatohepatitis, disease activity and fibrosis as dependent variables; and metabolic, inflammatory, HCV viral parameters and HIV as independent variables. Results: HIV infection was associated with greater area of steatosis (p = 0.07), greater waist:hip ratio (p = 0.04), thinner thigh skinfolds (p = 0.006). Steatosis was directly associated with serum insulin level (p = 0.04), HOMA (p = 0.05), sTNFR II (p = 0.02). Grade was related to HCV RNA (p = 0.04), AST (p = 0.004), total body fat (p = 0.07). Disease stage was associated directly with sTNFR II (p = 0.0001), and AST (p = 0.07), and inversely with HDL. By multiple regression steatosis was associated with increased sTNFR I and II, grade was related to IVDU, HCV viral load, gender, and stage was related to sTNFR II, HCV viral load, and glucose. Conclusions: Multiple factors affect hepatic histology in subjects with chronic HCV infection. While HCV viral load affects disease activity, the metabolic syndrome and TNF may be related to steatosis and fibrosis.

Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C

Obesity associated hepatic steatosis has been suggested to have a premalignant potential. We determined whether hepatic steatosis predisposes to liver cancer in persons with chronic hepatitis C virus (HCV) infection. We compared the histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4; and controls were matched for these characteristics. Those with a sustained virologic response to antiviral therapy were excluded. Duration of HCV infection, concomitant alcohol intake, body mass index and indices of past hepatitis B virus (HBV) infection were comparable between the groups. Controls were followed for a longer period after the index liver biopsy than were cases (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded by semiquantitative histological assessment, steatosis was comparable among cases and controls. The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC. Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients with chronic HCV infection.

Hepatobiliary and pancreatic: Insulinoma metastases with focal hepatic steatosis

A 44-year-old Japanese woman, who had been treated previously with distal pancreatectomy for an insulinoma, presented with recurrent symptoms of hypoglycemia. Her fasting serum glucose level was 30 mg/dL (reference range, 70–110 mg/dL) and her insulin level was 61 µU/mL (reference range, 3–17 µU/mL). An abdominal ultrasound study showed multiple hyperechoic nodules in the liver, the largest of which had a peripheral rim of increased echogenicity (Fig. 1). With abdominal magnetic resonance imaging, there were at least four areas of focal steatosis with low intensity on a gradient echo out-of-phase T1-weighted image (TR/TE, 200/4.2; Fig. 2). On the in-phase image, the low intensity lesions apparently disappeared, except for the smaller low intensity lesions within the focal steatosis (TR/TE, 200/2.2; Fig. 3). The low intensity areas that remained on the in-phase images were strongly enhanced after contrast was given. The lesions were surrounded by a low signal that might have been caused by focal steatosis (TR/TE, 3.7/0.96; Fig. 4). An ultrasound-guided percutaneous biopsy showed an insulinoma metastasis surrounded by hepatic steatosis. The hypoglycemic episodes resolved after treatment with hepatic arterial chemoembolization. Insulinoma metastases are rare because only a minority of insulinomas (10%) are malignant. Therefore, it is uncertain whether hepatic steatosis surrounding an insulinoma metastasis is a common phenomenon or a curiosity. Nevertheless, it seems plausible that local steatosis results from high local insulin levels that promote the synthesis and accumulation of lipid. This unusual pattern of focal hepatic steatosis can be seen and characterized on chemical shift magnetic resonance imaging.

Splanchnic and systemic hemodynamics in early abstinence and after ethanol administration in non-cirrhotic alcoholic patients

Thirteen asymptomatic chronic alcoholic patients were studied to investigate the early stages of portal hypertension in alcoholic liver disease and the effects of withdrawal and ethanol on hepatic function and hemodynamic variables. None of the patients presented clinical signs of decompensated liver disease, and their liver biopsies showed normal liver or moderate alterations only. In basal conditions and after an intravenous ethanol infusion (1 g/kg body weight), hepatic venous pressure gradient and hepatic blood flow using indocyanine green were measured through hepatic vein catheterization. Hepatic sinusoidal vascular resistance and indocyanine green intrinsic clearance were also calculated. Portal blood flow measurements were obtained by Doppler ultrasound. No correlation was observed between hepatic venous pressure gradient and histologic features, (steatosis, necrosis, fibrosis, inflammation and hepatocyte surface area). In basal conditions, portal hypertension was not found in any case. After ethanol, portal pressure increased significantly (p < 0.001); in four cases it rose to or above 5 mmHg. Portal blood flow, hepatic blood flow and hepatic vascular resistance also increased significantly. Intrinsic indocyanine green clearance decreased slightly but significantly. No significant correlations were found between portal pressure, hepatic resistance and the histologic parameters. It was concluded that alcoholic patients, without clinical or laboratory evidence of liver failure and with minimal or moderate histologic alterations, have normal portal pressures. After an intravenous ethanol load, however, four out of 13 patients (31%) reached levels of 5 mmHg or more, irrespective of their liver histology.