Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. We aimed to ...study the impact of the new definition on the epidemiology of fatty liver disease.
We randomly selected 1013 adults from the Hong Kong census database for clinical assessment, proton-magnetic resonance spectroscopy, and transient elastography. Five hundred sixty-five subjects without fatty liver at baseline underwent follow-up assessment. MAFLD was diagnosed as intrahepatic triglyceride content (IHTG) ≥5% and the presence of overweight/obesity, diabetes, or two other metabolic risk factors, with and without concomitant liver diseases. The diagnosis of NAFLD required the exclusion of concomitant liver diseases; metabolic factors were not considered.
The population prevalence of MAFLD and NAFLD was 25.9% (95% CI 23.2-28.7%) and 25.7% (95% CI 23.1-28.5%), respectively. Among 277 subjects with IHTG ≥5%, 247 (89.2%) fulfilled both the definitions of MAFLD and NAFLD. Fourteen subjects (5.1%) had IHTG ≥5% but did not meet the metabolic criteria of MAFLD. The incidence of MAFLD was 2.8 per 100 person-years at a median interval of 47 months (range 34-60 months). Among 78 subjects with incident NAFLD, 59 (75.6%) met the criteria of MAFLD; only one of the latter, a regular drinker, had liver stiffness ≥10 kPa.
The new definition of MAFLD does not significantly change the prevalence compared with NAFLD, but it may reduce the incidence by 25%. People with hepatic steatosis but not fulfilling the definition of MAFLD unlikely have significant liver disease.
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.
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.
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).
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.
Purpose
Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ ...quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC.
Theory and Methods
On‐resonance R1ρ (1/T1ρ) is mainly affected by the intrinsic R2 (1/T2), which is influenced by LIC. As on‐resonance R1ρ is closely related to the Carr–Purcell–Meiboom–Gill (CPMG) R2, and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ. The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ, a scaling factor was determined using the values of CPMG R2 and R1ρ, obtained simultaneously from a single breath‐hold from volunteers. The livers of 110 subjects were scanned to validate the correction method.
Results
LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ, LIC and the iron‐corrected R1ρ were not significantly correlated.
Conclusion
LIC can affect T1ρ in the liver. We developed an iron‐correction method for the quantification of T1ρ in the liver at 3.0T.
Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New ...non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population.
Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively.
Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54).
NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.
Purpose
In MRI, the macromolecular proton fraction (MPF) is a key parameter of magnetization transfer (MT). It represents the relative amount of immobile protons associated with semi‐solid ...macromolecules involved in MT with free water protons. We aim to quantify MPF based on spin‐lock MRI and explore its advantages over the existing MPF‐mapping methods.
Methods
In the proposed method, termed MPF quantification based on spin‐lock (MPF‐SL), off‐resonance spin‐lock is used to sensitively measure the MT effect. MPF‐SL is designed to measure a relaxation rate (Rmpfsl) that is specific to the MT effect by removing the R1ρ relaxation due to the mobile water and chemical exchange pools. A theory is derived to quantify MPF from the measured Rmpfsl. No prior knowledge of tissue relaxation parameters, including T1 or T2, is needed to quantify MPF using MPF‐SL. The proposed approach is validated with Bloch‐McConnell simulations, phantom, and in vivo liver studies at 3.0T.
Results
Both Bloch‐McConnell simulations and phantom experiments show that MPF‐SL is insensitive to variations of the mobile water pool and the chemical exchange pool. MPF‐SL is specific to the MT effect and can measure MPF reliably. In vivo liver studies show that MPF‐SL can be used to detect collagen deposition in patients with liver fibrosis.
Conclusion
A novel MPF imaging method based on spin‐lock MRI is proposed. The confounding factors are removed, and the measurement is specific to the MT effect. It holds promise for MPF‐sensitive diagnostic imaging in clinical settings.
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.
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).
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.
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.
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.
To document utility of shear-wave (SW) elastography for assessing liver fibrosis in chronic hepatitis B and to compare its performance with that of transient elastography.
Ethics committee approved ...the study, and informed consent was obtained. Patients with liver biopsy correlation (n = 226) and healthy patients (n = 171) were analyzed. Results of SW elastography of liver, SW elastography of spleen, and transient elastography of liver were compared and correlated according to METAVIR scores. Areas under the receiver operating characteristic curve (AUCs), binary logistic regression, and Delong test were used.
AUC for SW elastography of liver, transient elastography of liver, and SW elastography of spleen was, respectively, 0.86, 0.80, and 0.81 for fibrosis (≥ F1 stage); 0.88, 0.78, and 0.82 for moderate fibrosis (≥ F2 stage); 0.93, 0.83, and 0.83 for severe fibrosis (≥ F3 stage); and 0.98, 0.92, and 0.84 for cirrhosis (F4 stage). SW elastography of liver showed significantly higher accuracy than transient elastography of liver and SW elastography of spleen in all fibrosis stages (P = .01-.04). SW elastography of spleen showed similar accuracy with transient elastography of liver (P = .21-.99). Combination SW elastography of liver and SW elastography of spleen to predict fibrosis staging showed diagnostic accuracy not further improved compared with SW elastography of liver alone (similar AUC; ≥ F1, P = .87; ≥ F2, P = .81; ≥ F3, P = .84; ≥ F4, P = .88). SW elastography of liver had higher successful rate than transient elastography of liver (98.9% vs 89.6%). Prevalence of discordance in at least two stages with liver histologic staging was 10.2% (23 of 226) for SW elastography of liver and 28.2% (58 of 206) for SW elastography of spleen.
SW elastography provides more accurate correlation of liver elasticity with liver fibrosis stage compared with transient elastography, especially in identification of stage F2 or greater.
It is unknown if young medication-naïve bipolar II (BPII) depressed patients have increased white matter (WM) disruptions. 27 each of young (average 23 years) and treatment-naïve BPII depressed, ...unipolar depressed (UD) patients and age-sex-education matched healthy controls (HC) underwent 3 T MRIs with diffusion tensor imaging. Diagnostic ratings included Structured Clinical Interview for DSM Disorders (SCID), Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Hamilton Anxiety Rating Scale (HAM-A). Patients were clinically depressed (MADRS-BPII: 26.15 SD9.25, UD: 25.56 5.24, p = 0.86). Compared to UD, BPII had increased family bipolarity (BPII 13.6% vs UD 2.5%, p = 0.01, φc = 0.28), hypomanic symptoms (YMRS-BPII: 4.22 4.24, UD: 1.33 2, p = 0.02, d = 0.87), lifetime number of depressive episodes (BPII: 2.37 1.23, UD: 1.44 0.75, p = 0.02, d = 0.91), lifetime and current-year number of episodes (lifetime BPII: 50.85 95.47, UD: 1.7 1.03; current-year BPII: 9.93 16.29, UD: 1.11 0.32, ps = 0.04, ds = 0.73-0.77) and longer illness duration (BPII: 4.96 years 3.96, UD: 2.99 3.33, p = 0.15, d = 0.54). BPII showed no increased WM disruptions vs UD or HC in any of the 15 a priori WM tracts. UD had lower right superior longitudinal fasciculus (SLF) (temporal) axial diffusivity (AD) (1.14 vs 1.17 (BPII), 1.16 (HC); F = 6.93, 95% CI of Formula: see text: 0.00073, 5.22, ηp
= 0.15). Principal component analysis followed by exploratory linear discriminant analysis showed that increased R-SLF (temporal) AD, YMRS and family bipolarity distinguished BPII from UD (81.5% sensitivity, 85.2% specificity) independent of episode number and frequency. Young, medication-naïve adults with BPII depression did not show the WM disruptions distinguishing more chronically ill BP patients from UD. These WM disruptions may therefore be partly attributable to illness chronicity. Longitudinal studies should examine the trajectory of WM changes in BPII and UD and predictive validity of these baseline clinical and imaging parameters.
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•In this RCT, lifestyle intervention effectively led to remission of NAFLD in most non-obese and obese patients.•Weight reduction correlated with NAFLD remission in a dose-dependent ...manner.•The amount of weight reduction needed to achieve remission was less in non-obese patients.•By 6 years, non-obese patients remained more likely to maintain weight reduction and have ALT normalization.
Around 10–20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response.
A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m2 was used to define non-obese NAFLD.
Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m2, respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3–5% weight reduction; the same could only be achieved in obese patients with 7–10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group.
Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population.
Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3–10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.
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