Low-Dose d-Amphetamine Induced Regression of Liver Fat Deposits in Dercum Disease

Background

Dercum disease is a rare disorder of painful subcutaneous adipose tissue masses typically presenting as a constellation of signs and symptoms affecting most organs, including slow lymphatic flow and fatty liver.

Nonalcoholic Fatty Liver Disease Progression in Rats is Accelerated by Splenic Regulation of Liver PTEN/AKT

Background/Aim:

The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD), but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model.

Materials and Methods:

Following either splenectomy or sham operation, male Sprague–Dawley (SD) rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene expression, and the ratio of pAkt/Akt were determined.

Results:

Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers.

Conclusions:

The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression.     

The Relationship of Circulating Fetuin-A With Liver Histology and Biomarkers of Systemic Inflammation in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease

Background/Aims:

Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD).

Patients and Methods:

We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index.

Results:

Fetuin-A was negatively correlated with age (r = −0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis.

Conclusion:

This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.     

N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease

Background and Aims

Non-alcoholic fatty liver change is a common disease of the liver in which oxidative stress plays a basic role. Studies are largely focused on protecting the liver by means of anti-oxidative material. The aim of this study is to evaluate the role of N- acetylcysteine in the process of liver injury.

Methods

Thirty patients with non-alcoholic fatty liver steatosis were randomly selected to receive either N-acetylcysteine or vitamin C. Liver function tests (alanine aminotransfrase, aspartate aminotransfrase and alkaline phosphatase) were measured as well as the grade of steatosis, the pattern of its echogenicity, the span of the liver and the spleen and the portal vein diameter before the intervention. Patients were followed up using the same method of evaluation repeated in the first, second and third months.

Results

The mean age (SD) was 40.1(12.4) in patients receiving NAC and 46(10.4) years in patients receiving vitamin C (P = 0.137). NAC resulted in a significant decrease of serum alanine aminotransfrase after three months, compared to vitamin C. This effect was independent of the grade of steatosis in the initial diagnosis. NAC was able to significantly decrease the span of the spleen.

Conclusions

N-acetylcysteine can improve liver function in patients with non-alcoholic fatty liver disease. Better results may be achievable in a longer follow up.     

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease

BACKGROUND:

Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy.

OBJECTIVE:

To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD.

METHODS:

From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists.

RESULTS:

NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively.

CONCLUSION:

Xe-133 liver scan proved to be a safe, reliable, non-invasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.     

Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees

Background/Aims

The controlled attenuation parameter (CAP) implemented in FibroScan^® is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US).

Methods

Consecutive CAP results were retrospectively collected. A total of 280 subjects were included.

Results

Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34±28.39 dB/m for S0, 248.83±6.14 dB/m for S1, 274.33±8.53 dB/m for S2, and 322.35±22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP.

Conclusions

The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.     

Ideal Cardiovascular Health Is Inversely Associated with Nonalcoholic Fatty Liver Disease: A Prospective Analysis

Background

Cardiovascular health has been proven to be associated with major cardiometabolic diseases. However, little is known of associations between cardiovascular health and nonalcoholic fatty liver disease.

The Relationship between Intestinal Motility and Interstitial Cells of Cajal in Nonalcoholic Fatty Liver Mice

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in western world. However, NAFLD shows an increasing trend in China every year, which has attracted the attention of national health authorities. The previous studies have shown that NAFLD caused severe gastrointestinal motor disorders, but little is known about the interstitial cells of Cajal (ICC) role in gastrointestinal motor disorders.

Objectives

The aim of this study was to observe the ICC in jejunum of nonalcoholic fatty liver mice by immunohistochemistry and assessed the relationship between intestinal motility and ICC.

Materials and Methods

Thirty five Sprague-Dawley (SD) rats were randomly divided into nonalcoholic fatty liver (n = 25) and control groups (n = 10), rats were housed individually in cages and had free access to food and water, nonalcoholic fatty liver group was duplicated by high-fat diet (consisted of ordinary food, 20 g/kg cholesterol and 100 g/kg fat) feeding. Dextran blue-2000 was used to monitor the intestinal motility. The proximal small intestine was harvested to investigate the C-kit positive ICC. The hepatic tissue slices were used for pathological observation.

Results

Nonalcoholic fatty liver disease was successfully established. The intestinal motility in nonalcoholic fatty liver group (49.5 ± 10.9) was weaker compared to the control group (57.3 ± 8.9), P < 0.05. The rate of ICC also have shown statistically significant differences between nonalcoholic fatty liver (4.87 ± 2.97/mm ²) and control groups (6.54 ± 3.13/mm ²), P < 0.05.

Conclusions

ICC may be related to the intestinal motility in nonalcoholic fatty liver mice.     

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non‐alcoholic fatty liver disease

Aims/Introduction

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease.

Materials and Methods

Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method.

Results

The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = −0.45, P < 0.001; grade r = −0.54, P < 0.001; stage r = −0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = −0.22, P < 0.05) and grade (coefficient = −0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = −0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = −0.62, P = 0.059).

Conclusions

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.     

Insulin Resistance, Steatosis, and Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background/Aim:

Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection.

Patients and Methods:

Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis.

Results:

Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST) level were 42 ± 7.7 years (range 20-56) and 68 ± 41.7 U/L (range 16-214), respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4) and 5.9 ± 15.2 (range 0.9-136.2), respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis.

Conclusions:

Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.     

Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in Children with Nonalcoholic Fatty Liver Disease

Objective:

To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease (NAFLD).

Methods:

One hundred and eight obese (body mass index (BMI) >95th percentile for age and sex) adolescents with NAFLD were included in the study. Mean age of the subjects was 13.8±3.9 years (9-17 yrs). The diagnosis of NAFLD was based on the presence of liver steatosis with high transaminases. The subjects were randomly divided into two groups. Group 1 (PUFA group, n=52) received a 1000 mg dose of PUFA once daily for 12 months and lifestyle intervention. Group 2 (placebo group, n=56) received a recommended diet plus placebo and lifestyle intervention for 12 months. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from fasting samples.

Results:

BMI, fasting insulin levels and HOMA-IR values in both groups decreased significantly at the end of the study. In group 1, 67.8% of the patients had a decrease from baseline in the prevalence of steatosis (p<0.001). Frequency of elevated alanine aminotransferase (ALT) levels (39.2% to 14.2%; p<0.01) and elevated aspartate aminotransferase (AST) levels (25% to 17.8%; p=0.01) decreased significantly in the PUFA group. Following a 12-month diet plus placebo and lifestyle intervention treatment, 40.3% (21) of the patients in the placebo group also showed a decrease in frequency of steatosis (p=0.04) and slight decreases in frequency of elevated ALT levels (38.4% to 28.8%; p=0.01) and AST levels (30.7% to 28.8%; p>0.05).

Conclusion:

Our results indicated that n-3 PUFA treatment is safe and efficacious in obese children with NAFLD and can improve ultrasonographic findings and the elevated transaminase levels.     

Does Vitamin E Improve the Outcomes of Pediatric Nonalcoholic Fatty Liver Disease? A Systematic Review and Meta-analysis

Background and Aims:

To systemically evaluate the efficacy of adjuvant vitamin E on the outcomes of nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH) in children.

Materials and Methods:

We searched MEDLINE, PUBMED, EMBASE, the Cochrane Central Register Controlled Trials, and the Cochrane Database of Systematic Reviews over the period between January 1980 and September 2012 for the studies that examined the role of adjuvant vitamin E given at any dose or duration, alone or in combination with other interventions, on the outcome of pediatric NAFLD. The outcomes are alanine aminotransferase (ALT) normalization and histological improvement.

Results:

Five randomized trials were eligible to be included in our analysis, with a total of 270 participants. There was no statistically significant difference in the effect of adjuvant vitamin E on normalizing serum ALT [risk ratio (RR) =1.18, confidence interval (CI) =0.92-1.53, P = 0.77 for heterogeneity, I² = 0%]. Sensitivity analysis showed that using higher doses of vitamin E, a longer duration of therapy or adding vitamin C did not change the effect on the measured outcome. Only two studies looked at histological changes as an outcome. We observed substantial heterogeneity between the two studies.

Conclusions:

Our meta-analysis did not find a significant effect of adjuvant vitamin E over placebo in normalizing serum ALT. Data on the long-term effect of adjuvant vitamin E on histological improvements in NAFLD patients are still lacking. Larger, well-designed randomized controlled trials (RCTs) in children with histological endpoints are still needed to answer this question.     

Pattern of Liver Function Tests in Morbidly Obese Saudi Patients Undergoing Bariatric Surgery

Background/Aim:

Morbidly obese patients have a high prevalence of fatty liver disease and its serious complications, and high prevalence of abnormal liver function tests (LFT). The LFT can give a clue to the liver damage and correlate with activity. We aim to study the pattern of LFT in morbidly obese Saudi patients undergoing bariatric surgery in Eastern region.

Patients and Methods:

Medical records of patients undergoing bariatric surgery were reviewed. Demographic data, comorbid conditions, and medications taken were recorded. Intraoperative liver appearance was noted. Patients with alcohol intake or without LFT were excluded.

Results:

Out of 113 patients, 15 patients were excluded, and of the remaining 98 patients analyzed, 58.2% were females. Mean age was 33.1 ± 8.87 years. Mean body mass index (BMI) was 53.7 ± 1.27 kg/m². Abnormal LFT (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) alkaline phosphatase (ALK), and Gamma glutamyl transpeptidase (GTT) were observed in 17.3%, with 1.5 to 2 times the upper limit of normal. ALT was most elevated in 12.2%. Abdominal ultrasonography was done in 67 (68.4%) patients, of whom 51 (76%) had fatty liver. Comorbid conditions including diabetes mellitus, hypertension, hyperlipidemia, bronchial asthma, and obstructive sleep apnea were observed in 51 (51.50%) patients, eight of them (16.3%) had abnormal LFT. No intraoperative changes of cirrhosis were observed.

Conclusion:

The prevalence of abnormal LFT is low in morbidly obese patients from the eastern region of Saudi Arabia. A prospective study with a larger sample and liver biopsy, is needed to clarify the findings.     

Gallstone Disease Does Not Predict Liver Histology in Nonalcoholic Fatty Liver Disease

Background/Aims

We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score.

Methods

We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy.

Results

Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84).

Conclusions

The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.     

Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease

Background/Aims

The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD).

Methods

Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3).

Results

A total of 186 patients were included: 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, p<0.001), and there was no significant difference between the NAFLD and ALD groups (ρ=0.569, p<0.001; ρ=0.519, p<0.001; p=0.635). Using CAP, area under receiver operating characteristic curves for ≥S2 and ≥S3 steatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥90%, CAP cutoffs for the detection of ≥S2 and ≥S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups.

Conclusions

The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.     

Increased insulinogenic index is an independent determinant of nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance

Background

Although insulin resistance is involved in nonalcoholic fatty liver disease, role of abnormalities in early phase of insulin secretion has not been examined.

Aims

We examined which anthropometric and metabolic parameters, including insulinogenic index during oral glucose tolerant test, were independently associated with the disease activity of nonalcoholic fatty liver disease.

Methods

A total of 114 consecutive biopsy-proven nonalcoholic fatty liver disease patients without type 2 diabetes were enrolled.

Results

Age, aspartate aminotransferase, free fatty acid, ferritin type IV collagen, hyaluronic acid, procollagen N-terminal peptide, fasting plasma glucose and 2-h insulin after glucose loading were significantly higher in patients with impaired glucose tolerance than those with normal glucose tolerance. Multiple stepwise regression analysis revealed that glycated haemoglobin, decreased density ratio of liver to spleen in computed tomography and increased insulinogenic index were independently associated with nonalcoholic fatty liver disease activity score in normal glucose tolerance patients, whereas aspartate aminotransferase and 2-h insulin in impaired glucose tolerance subjects. However, there were no significant independent correlations between insulinogenic index and steatosis grade/fibrosis stage in normal glucose tolerance patients.

Conclusion

The present study suggests that increased early phase of insulin secretion may contribute to nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance.     

Comparison of portal vein doppler indices and hepatic vein doppler waveform in patients with nonalcoholic fatty liver disease with healthy control

Background

The purpose of the present study is to investigate the association of nonalcoholic fatty liver disease (NAFLD) with the doppler waveform pattern of hepatic veins and portal vein doppler indices.

Objectives

This assay may be useful in evaluating the natural course of NAFLD and monitor treatment efficacy on follow-up.

Patients and Methods

This case control study was performed in 31 patients with NAFLD and 31 normal healthy adults who served as the control group. The patients presented with elevated liver enzymes levels (ALT/AST) and hyperechogenic livers in the B-mode ultrasonography examination. Eleven patients had a liver biopsy. After an 8-hour fast,B-mode and duplex doppler ultrasonography were performed, and the waveform patterns of the right hepatic vein, portal vein diameter, grade of fatty liver, portal vein pulsatility index (VPI), and mean flow velocity (MFV) were measured.

Results

VPI and MFV values were 0.42 ± 0.92 and 17.27 ± 5.34 cm/second, respectively, in the control group and 0.25 ± 0.50 and 12.82 ± 4.32 cm/second in patients with NAFLD (P< 0.01). The frequency of abnormal hepatic vein doppler waveform patterns (biphasic or monophasic) was significantly higher in patients with NAFLD (55.2%) versus control subjects (3.2%) (P < 0.001). There was no correlation between the degree of fat infiltration and VPI (P = 0.714), MFV (P = 0.911), or hepatic vein waveform pattern (P = 0.197). We found no correlation between liver enzyme levels and MFV or VPI. However, the rate of abnormal hepatic vein was higher in patients with enzyme levels that exceeded twice the normal value (P = 0.05).

Conclusions

Patients with NAFLD have a high rate of abnormal hepatic vein doppler waveform patterns, and decreased VPI and MFV are suggestive of reduced vascular compliance in the liver. Elevated liver enzymes levels do not influence VPI or MFV, but patients with abnormal enzymes have higher rates of abnormal hepatic vein doppler waveform patterns.