Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer's Disease.

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

Fatty Pancreas Is Independently Associated With Subsequent Diabetes Mellitus Development: A 10-Year Prospective Cohort Study.

BACKGROUND & AIMS: Although the association between fatty pancreas and metabolic syndrome has been suggested in retrospective studies, long-term prospective data on the effect of fatty pancreas on various metabolic outcomes are lacking. We aimed to prospectively investigate the association between fatty pancreas and the development of major metabolic outcomes. METHODS: A total of 631 subjects from a population study using fat-water magnetic resonance imaging to quantify pancreatic and liver fat content during 2008 to 2010 were followed up prospectively until December 2020 (mean follow-up time, 11.1 ± 1.1 y). Subjects with significant alcohol intake and diabetes mellitus (DM) at baseline were excluded. Incidence of newly diagnosed DM, hypertension, dyslipidemia, ischemic heart disease, cardiovascular accidents, pancreatic cancer, and mortality were evaluated. RESULTS: Among the 631 subjects (mean age, 48 ± 11 y), 93 (14.7%) had fatty pancreas. The fatty pancreas group had a higher incidence of DM (33.3% vs 10.4%; P < .001), hypertension (37.7% vs 22.7%; P = .003), and dyslipidemia (37.7% vs 14.6%; P < .001) during long-term follow-up evaluation. Individuals with both fatty liver and pancreas had the highest DM incidence, followed by fatty liver only and fatty pancreas only groups (P < .001). Fatty pancreas was associated independently with DM (adjusted hazard ratio, 1.81; 95% CI, 1.10-3.00; P = .020), but not hypertension or dyslipidemia on multivariate analysis. Each percentage increase of pancreatic fat increased the risk of incident DM by 7% (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13; P = .016). No participants developed pancreatic cancer during the follow-up period. CONCLUSIONS: Fatty pancreas is associated independently with subsequent DM development, but not hypertension or dyslipidemia.

Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

OBJECTIVE: To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APTmean, APT90, APTskewness, and APTkurtosis, respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis. RESULTS: Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APTskewness (HR = 1.98; p = 0.034), DMFS with APTmean (HR = 2.44; p = 0.033), and APT90 (HR = 1.93; p = 0.009), and DFS with APTmean (HR = 2.01; p = 0.016), APT90 (HR = 1.68; p = 0.009), and APTskewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005). CONCLUSION: APTw imaging may potentially predict survival in patients with NPC. KEY POINTS: • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APThigh group is at higher risk of disease relapse than the APTlow group.

Pre-treatment intravoxel incoherent motion diffusion-weighted imaging predicts treatment outcome in nasopharyngeal carcinoma.

PURPOSE: To evaluate whether pre-treatment intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can predict treatment outcome after 2 years in patients with nasopharyngeal carcinoma (NPC). METHOD: One hundred and sixty-one patients with newly diagnosed NPC underwent pre-treatment IVIM-DWI. Univariate Cox regression analysis was performed to evaluate the correlation of the mean values of the pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction and apparent diffusion coefficient with local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastases-free survival (DMFS) and disease-free survival (DFS). Significant diffusion parameters, together with staging, age, gender and treatment as confounding factors, were added into a multivariate model. The area under the curves (AUCs) of significant parameters for disease relapse were compared using the Delong test. RESULTS: Disease relapse occurred in 30 % of the patients at a median follow-up time of 52.1 months. The multivariate analysis showed that high D and T-staging were correlated with poor LRFS (p = 0.042 and 0.020, respectively) and poor DFS (p = 0.023 and 0.001, respectively); low D* and high T-staging with poor RRFS (p = 0.020 and 0.033, respectively); and high N-staging with poor DMFS (p = 0.006). D with the optimal threshold of ≥0.68 × 10-3 mm2/s and T-staging showed similar AUCs (AUC = 0.614 and 0.651, respectively; p = 0.493) for predicting disease relapse. CONCLUSION: High D and low D* were predictors of poor locoregional outcome but none of the diffusion parameters predicted DMFS in NPC.

Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.

PURPOSE: To determine if treatment of nasopharyngeal carcinoma (NPC) induces early changes in amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI), and to perform a preliminary evaluation of APTw imaging in response assessment. METHODS: Sixteen patients with NPC planned for treatment with radiotherapy and/or chemotherapy underwent APTw imaging of the primary tumour pre-treatment and 2-week intra-treatment. Difference in pre- and intra-treatment APT mean (APTmean) was compared using the Wilcoxon signed rank test. Differences in APTmean and percentage change (%Δ) in APTmean were compared between responders and non-responders based on the outcome at 6 months, using the Mann-Whitney U test. RESULTS: APTmean decreased in 9/16 (56.3%) and increased in 7/16 (43.7%) with no significant difference between the pre- and intra-treatment APT values for the whole group (p > 0.05). NPC showed response in 11/16 (68.8%) and non-response in 5/11 (31.2%). There were significant differences between the %Δ of responders and non-responders for APTmean (p = 0.01). Responders showed %Δ decrease in APTmean of - 23.12% while non-responders showed a %Δ increase in APTmean of + 102.28%. CONCLUSION: APT value changes can be detected in early intra-treatment. Intra-treatment %Δ APTmean shows potential in predicting short-term outcome.

Diffusion-weighted imaging of nasopharyngeal carcinoma to predict distant metastases.

Our study aimed to identify diffusion-weighted imaging (DWI) parameters obtained from primary nasopharyngeal carcinoma (NPC) at initial presentation, that can predict patients at risk of distant metastases. One hundred and sixty-four patients underwent pretreatment magnetic resonance imaging and DWI. The apparent diffusion coefficient (ADC)mean, ADCskewness, and ADCkurtosis were obtained by histogram analysis. Univariate and multivariate analyses of these ADC parameters together with primary volume (PV), nodal volume (NV), T stage, N stage and presence of locoregional relapse (LRR) were compared between patients with distant metastases (DM+) and patients without distant metastases (DM-) at 5 years using logistic regression. Twenty-eight out of 164 patients (17.1 %) were DM+ (2.5-60 months) and 136/164 patients were DM- (61.2-119.4 months). Compared to DM- patients, the primary tumour of DM+ patients showed significantly lower ADCskewness (ADC values with the greatest frequency were higher) (p = 0.041), and higher PV (p = 0.022), NV (p < 0.01), T stage (p = 0.023), N stage (p < 0.01) and LRR (p < 0.01). On multivariate analysis the ADCskewness was no longer significant (p = 0.120) and only NV and LRR were independent predictors for DM+ (p = 0.023 and 0.021, respectively). DWI showed that compared to DM- patients, DM+ patients had a significantly lower primary tumour ADCskewness, but at initial presentation NV was the only independent predictor of DM.

Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A Population Study Using Proton-Magnetic Resonance Spectroscopy.

Dietary pattern analysis is an alternative approach to examine the association between diet and nonalcoholic fatty liver disease (NAFLD). This study examined the association of two diet-quality scores, namely Diet Quality Index-International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence. Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above were recruited through a population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. DQI-I and MDS, as well as major food group and nutrient intakes were calculated based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at ≥5% by proton-magnetic resonance spectroscopy. Multivariate logistic regression models were used to examine the association between each diet-quality score or dietary component and prevalent NAFLD with adjustment for potential lifestyle, metabolic and genetic factors. A total of 220 subjects (27.6%) were diagnosed with NAFLD. DQI-I but not MDS was associated with the prevalence of NAFLD. A 10-unit decrease in DQI-I was associated with 24% increase in the likelihood of having NAFLD in the age and sex adjusted model (95% CI: 1.06-1.45, p = 0.009), and the association remained significant when the model was further adjusted for other lifestyle factors, metabolic and genetic factors [OR: 1.26 (95% CI: 1.03-1.54), p = 0.027]. Multivariate regression analyses showed an inverse association of the intake of vegetables and legumes, fruits and dried fruits, as well as vitamin C with the NAFLD prevalence (p<0.05). In conclusion, a better diet quality as characterized by a higher DQI-I and a higher consumption of vegetables, legumes and fruits was associated with a reduced likelihood of having NAFLD in Hong Kong Chinese.

Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy.

OBJECTIVES: Some studies suggest that non-obese patients with nonalcoholic fatty liver disease (NAFLD) may have more severe disease. We aim to study the epidemiology and severity of non-obese NAFLD. METHODS: A total of 911 community subjects were randomly recruited from the census database of the Hong Kong Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese NAFLD. RESULTS: The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5% in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs. 5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c, insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent factors associated with NAFLD in non-obese subjects. Even among non-obese subjects with normoglycemia, those with NAFLD were more insulin resistant (mean homeostasis model assessment of insulin resistance: 2.0±1.0 vs. 1.1±1.1; P<0.001). CONCLUSIONS: One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.

Higher estimated net endogenous Acid production may be associated with increased prevalence of nonalcoholic Fatty liver disease in chinese adults in Hong Kong.

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto's method and potential renal acid load (PRAL) was calculated using Remer's method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to ascertain the link between diet-induced acid load and NAFLD and to investigate the underlying mechanisms.

Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy.

BACKGROUND & AIMS: Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests. METHODS: This was a prospective cohort study. The intrahepatic triglyceride (IHTG) content was measured serially with proton-magnetic resonance spectroscopy in community subjects. Transient elastography was performed to assess liver fibrosis. RESULTS: 565 subjects (mean age 48 years, 62.7% women) without NAFLD at baseline underwent follow-up assessment after a median interval of 47 months (range 34-60 months). 78 (13.8%) subjects developed incident fatty liver with a mean IHTG content of 8.9% (SD 5.3%). 16 (20.5%) subjects had an IHTG content ⩾ 11.0% suggestive of moderate to severe steatosis. After excluding 2 men with significant alcohol consumption, the population incidence of NAFLD at 3-5 years was 13.5% (95% CI 10.6-16.3%; 3.4% per year). Only 1 subject with incident NAFLD had high liver stiffness (11.1 kPa) suggestive of advanced fibrosis. Metabolic syndrome at baseline was the strongest predictor of incident fatty liver. Incident central obesity developed in 31.0% of subjects with incident fatty liver and 5.6% of those without (p<0.001). No subject with incident fatty liver had regression of impaired fasting glucose, which occurred in 51.1% of those without incident fatty liver (p=0.001). CONCLUSIONS: 13.5% of the Hong Kong Chinese adult population develop NAFLD in 3-5 years, but few have severe steatosis or advanced fibrosis. Metabolic syndrome is the most important risk factor of incident NAFLD.

PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin-like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients. METHODS: This was a post-hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy. RESULTS: One hundred and fifty-four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist-to-hip ratio (P = 0.024), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group. CONCLUSION: Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.

Fatty pancreas, insulin resistance, and ß-cell function: a population study using fat-water magnetic resonance imaging.

OBJECTIVES: Nonalcoholic fatty liver disease is the most common chronic liver disease. Fatty pancreas has also been described but is difficult to assess. It is now possible to measure pancreatic and liver fat accurately with magnetic resonance imaging (MRI). We aimed to define the normal range of pancreatic fat and identify factors associated with fatty pancreas. In addition, the effect of fatty liver and fatty pancreas on insulin resistance (IR) and pancreatic ß-cell function was studied. METHODS: Fat-water MRI and proton-magnetic resonance spectroscopy were performed on 685 healthy volunteers from the general population to measure pancreatic and liver fat, respectively. On the basis of fasting plasma glucose and insulin levels, the IR and ß-cell function were assessed using the homeostasis model assessment (HOMA). RESULTS: Among subjects without significant alcohol consumption or any component of metabolic syndrome, 90% had pancreatic fat between 1.8 and 10.4%. Using the upper limit of normal of 10.4%, 110 (16.1%; 95% confidence interval 13.3-18.8%) subjects had fatty pancreas. On multivariable analysis, high serum ferritin, central obesity, and hypertriglyceridemia were independent factors associated with fatty pancreas. Subjects with both fatty pancreas and fatty liver had higher HOMA-IR than did those with either condition alone. Fatty pancreas was not associated with HOMA-ß after adjusting for liver fat and body mass index. CONCLUSIONS: In all, 16.1% of this community cohort of adult Hong Kong Chinese volunteers had a fatty pancreas by our definition. Central obesity, hypertriglyceridemia, and hyperferritinemia are associated with fatty pancreas. Individuals with fatty pancreas have increased IR.

Non-Gaussian analysis of diffusion weighted imaging in head and neck at 3T: a pilot study in patients with nasopharyngeal carcinoma.

PURPOSE: To technically investigate the non-Gaussian diffusion of head and neck diffusion weighted imaging (DWI) at 3 Tesla and compare advanced non-Gaussian diffusion models, including diffusion kurtosis imaging (DKI), stretched-exponential model (SEM), intravoxel incoherent motion (IVIM) and statistical model in the patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: After ethics approval was granted, 16 patients with NPC were examined using DWI performed at 3T employing an extended b-value range from 0 to 1500 s/mm(2). DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models on primary tumor, metastatic node, spinal cord and muscle. Non-Gaussian parameter maps were generated and compared to apparent diffusion coefficient (ADC) maps in NPC. RESULTS: Diffusion in NPC exhibited non-Gaussian behavior at the extended b-value range. Non-Gaussian models achieved significantly better fitting of DWI signal than the mono-exponential model. Non-Gaussian diffusion coefficients were substantially different from mono-exponential ADC both in magnitude and histogram distribution. CONCLUSION: Non-Gaussian diffusivity in head and neck tissues and NPC lesions could be assessed by using non-Gaussian diffusion models. Non-Gaussian DWI analysis may reveal additional tissue properties beyond ADC and holds potentials to be used as a complementary tool for NPC characterization.

Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis--a longitudinal study.

BACKGROUND: The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied. METHODS: Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG). RESULTS: A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P=0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2)=0.4820, P=0.0028) and increase in Bacteroidetes (R(2)=0.4366, P=0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment. CONCLUSIONS: NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.

Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND & AIMS: Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD. METHODS: This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy. RESULTS: 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; p<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (p<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (p<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome. CONCLUSIONS: The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients.

The use of dynamic tracer concentration in veins for quantitative DCE-MRI kinetic analysis in head and neck.

BACKGROUND: Head and neck Magnetic Resonance (MR) Images are vulnerable to the arterial blood in-flow effect. To compensate for this effect and enhance accuracy and reproducibility, dynamic tracer concentration in veins was proposed and investigated for quantitative dynamic contrast-enhanced (DCE) MRI analysis in head and neck. METHODOLOGY: 21 patients with head and neck tumors underwent DCE-MRI at 3T. An automated method was developed for blood vessel selection and separation. Dynamic concentration-time-curves (CTCs) in arteries and veins were used for the Tofts model parameter estimations. The estimation differences by using CTCs in arteries and veins were compared. Artery and vein voxels were accurately separated by the automated method. Remarkable inter-slice tracer concentration differences were found in arteries while the inter-slice concentration differences in veins were moderate. Tofts model fitting by using the CTCs in arteries and veins produced significantly different parameter estimations. The individual artery CTCs resulted in large (>50% generally) inter-slice parameter estimation variations. Better inter-slice consistency was achieved by using the vein CTCs. CONCLUSIONS: The use of vein CTCs helps to compensate for arterial in-flow effect and reduce kinetic parameter estimation error and inconsistency for head and neck DCE-MRI.

Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study.

BACKGROUND: Probiotics have profound effect on nonalcoholic steatohepatitis (NASH) in animal models. We aimed to test the hypothesis that probiotics treatment was superior to usual care in reducing liver fat in NASH patients. MATERIAL AND METHODS: Patients with histology-proven NASH were randomized to receive probiotics (n = 10) or usual care (n = 10) for 6 months. The Lepicol probiotic formula contained Lactobacillus plantarum, Lactobacillus deslbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum. The primary endpoint was change in intrahepatic triglyceride content (IHTG), as measured by proton-magnetic resonance spectroscopy, from baseline to month 6. Secondary endpoints included changes in liver biochemistry and metabolic profile. RESULTS: IHTG decreased from 22.6 ± 8.2% to 14.9 ± 7.0% in the probiotic group (P = 0.034) but remained static in the usual care group (16.9 ± 6.1% to 16.0 ± 6.6%; P = 0.55). Six subjects in the probiotic group had IHTG reduced by more than 30% from baseline, compared to 2 subjects in the usual care group (P = 0.17). The probiotic group also had greater reduction in serum aspartate aminotransferase level (P = 0.008). On the other hand, the use of probiotics was not associated with changes in body mass index, waist circumference, glucose and lipid levels. CONCLUSIONS: Probiotics treatment may reduce liver fat and AST level in NASH patients. The therapeutic potential of probiotics in NASH should be tested in larger studies.

Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients.

Niacin reduces plasma triglycerides, but it may increase free fatty acids and insulin resistance during long-term treatment. We examined the effect of extended-release niacin on liver fat content in Chinese patients with dyslipidemia and whether the common diacylglycerol acyltransferase-2 (DGAT2) polymorphisms influenced this effect. The 39 patients (baseline liver fat content: 12.8 ± 7.6%, triglycerides: 3.30 ± 1.67 mmol/l) were treated with niacin, gradually increasing the dose to 2 g/day for a total of 23 weeks. The liver fat content and visceral/subcutaneous fat was measured before and after treatment. Subjects were genotyped for the DGAT2 rs3060 and rs101899116 polymorphisms. There were significant (P < 0.001) reductions in plasma triglycerides (-34.9 ± 37.6%), liver fat content (-47.2 ± 32.8%), and visceral fat (-6.3 ± 15.8%, P < 0.05) after niacin treatment. Mean body weight decreased by 1.46 ± 2.7% (1.17 ± 2.44 kg, P < 0.001) during the study, but liver fat changes remained significant after adjustment for age, gender, and body weight changes [mean absolute change (95% CI): -6.1% (-8.0, -4.3), P < 0.001]. The DGAT2 variant alleles were associated with a smaller reduction in liver fat content in response to niacin after adjustment for other covariates (P < 0.01). These findings suggest that niacin treatment may reduce liver fat content in Chinese patients with dyslipidemia and that the mechanism may involve inhibition of DGAT2. However, the findings might have been confounded by the small but significant reductions in body weight during the study. Future large randomized controlled trials are needed to verify these findings.

Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers.

BACKGROUND & AIMS: The diagnosis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is limited by the need for liver biopsy. We aimed at testing the accuracy of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) for the diagnosis of NAFLD and NASH. METHODS: 146 patients with biopsy-proven NAFLD and 74 age- and gender-matched healthy controls were included. Serum CK-18, AFABP and FGF21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum CK-18, AFABP, and FGF21 increased in a stepwise fashion in control subjects (median 103 U/L, 15.4 ng/ml, and 104 pg/ml), patients with non-NASH NAFLD (263 U/L, 18.9 ng/ml, and 249 pg/ml) and NASH (418 U/L, 19.4 ng/ml, and 354 pg/ml) (p<0.001, 0.060, and 0.016, respectively). The area under receiver-operating characteristics curve to diagnose NAFLD and NASH was 0.91 and 0.70 for CK-18, 0.66 and 0.59 for AFABP, and 0.84 and 0.62 for FGF21. At cut-offs of 203 and 670 U/L, CK-18 had 71% negative predictive value (NPV) and 77% positive predictive value (PPV) to exclude and diagnose NASH. A 2-step approach measuring CK-18 followed by FGF21 further improved the NPV to 74% and PPV to 82%. In a validation cohort of 51 patients with paired liver biopsies, the NPV and PPV of the 2-step approach were 67% and 78%, respectively. CONCLUSIONS: CK-18 is the most accurate biomarker for NAFLD and NASH. A two-step approach using CK-18 and FGF21 further improves the accuracy in diagnosing NASH.

Hepatitis B virus infection and fatty liver in the general population.

BACKGROUND & AIMS: In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection in the general population. METHODS: We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy. RESULTS: One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2-33.3) in HBV patients and 2.1% (0-44.2) in controls (p <0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval [CI] 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls (p=0.003). The fatty liver prevalence differed in HBV patients and controls aged 40-59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p=0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p=0.034), but the difference was mainly attributed to lower triglyceride levels. Among HBV patients, viral genotypes, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver. CONCLUSIONS: HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies.