Nonalcoholic Fatty Liver Disease Remission Research Articles

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women.

The association between nonalcoholic fatty liver disease (NAFLD) and free triiodothyronine (FT3) in euthyroid subjects was in dispute. We aimed to investigate this issue in a population-based cohort study. A total of 3144 euthyroid subjects at baseline from the Shanghai Nicheng Atherosclerosis Study were selected for the cross-sectional analysis, and 2089 subjects being followed up after 2.2years were selected for the longitudinal analysis. NAFLD was diagnosed by ultrasound. The cut-off point of elevated alanine aminotransferase (ALT) level was 40U/L. The FIB-4 index was used to assess the risk of advanced liver fibrosis. Age-adjusted mean levels of FT3 and FT3/free thyroxine (FT4) ratio were higher in subjects with NAFLD than those without NAFLD and linearly increased with a higher risk of NAFLD progression (assessed by levels of ALT and FIB-4 index) in euthyroid women but not in men. After adjustment for confounding variables, FT3 levels significantly increased with the presence of NAFLD (β=0.1, P<0.001) and linearly increased with a higher risk of NAFLD progression in euthyroid women. After a 2.2-year follow-up, FT3 levels increased with the occurrence of NAFLD (mean change percentage: 1.4%) and decreased with the remission of NAFLD (mean change percentage: -2.7%) in euthyroid women. There are positive associations of FT3 levels with NAFLD and the risk of NAFLD progression in euthyroid women. The changes in FT3 levels with the alteration of NAFLD status may be an adaptive response to maintain energy and metabolic homeostasis.

Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease

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.

Non-alcoholic fatty liver disease incidence, remission and risk factors among a general Chinese population with a 6-year follow-up

This study aimed to investigate the incidence, remission and risk factors of non-alcoholic fatty liver disease (NAFLD) among a general population with a 6-year follow-up. In total, 691 individuals from the general population in Jilin, China aged 20–75 years participated in two independent cross-sectional surveys carried out in 2007 and 2013. After excluding patients with alcoholism, viral hepatitis and other liver diseases, 646 individuals were finally enrolled in our study. Of the 646 subjects, 512 did not have NAFLD at baseline, while 134 did. Of the 512 individuals without NAFLD at baseline, 188 (36.7%) developed NAFLD during the six-year follow-up period. The baseline body mass index (BMI, OR = 1.49, 1.36–1.64), high-density lipoprotein cholesterol level(HDL-C) (OR = 0.35, 0.16–0.76) and weight gain (OR = 1.22, 1.16–1.29) were independent predictors for NAFLD incidence. Of the 134 subjects with NAFLD at baseline, 33 (24.6%) had no evidence of NAFLD after 6 years. Males (OR = 4.85, 1.98–11.92) and baseline BMI levels (OR = 0.81, 0.70–0.94) were associated with NAFLD remission. Among the general population, the incidence of NAFLD mainly depended on baseline weight and weight gain. Subjects with mild baseline weights and male subjects were prone to NAFLD remission.

Progression and new onset of nonalcoholic fatty liver disease in living kidney donors compared to healthy controls.

There is growing evidence linking nonalcoholic fatty liver disease (NAFLD) with reduced glomerular filtration rate (GFR). Living kidney donors do not have underlying kidney disease, but have reduced GFR as a result of nephrectomy. Whether kidney donation is associated with a higher risk for development or progression of NAFLD is currently unknown. Retrospective evaluation of metabolic parameters and sonographic evidence of NAFLD were performed in 232 living kidney donors and 162 healthy controls. A total of 25 donors and 44 controls had NAFLD at baseline. During a mean follow-up of 6.8years, 6 donors (24%) and 17 controls (38.6%) (P=.29) had a remission of NAFLD, related with decreased body mass index (BMI). The progression of NAFLD fibrosis score was similar in both groups. New onset of NAFLD was observed in 14 (6.8%) donors and 13 (11.01%) controls (P=.211), and was related to increased BMI and a higher baseline Fatty Liver Index score. Neither eGFR nor urine albumin excretion in the donors were related to new onset or progression of NAFLD. Reduced kidney function secondary to kidney donation is not associated with increased incidence or progression of NAFLD.

Associations of hyperuricemia and obesity with remission of nonalcoholic fatty liver disease among Chinese men: A retrospective cohort study.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that is associated with high serum uric acid (SUA) levels, although the effects of high SUA levels on NAFLD remission remain unclear. In addition, it is unclear whether obesity and high SUA levels have a combined effect on NAFLD remission. This retrospective cohort study evaluated male employees of seven Chinese companies and investigated the association between high SUA levels and NAFLD remission, as well as the potential combined effect of high SUA levels and obesity on NAFLD remission. The study followed 826 men with NAFLD for 4 years, and the NAFLD remission rate was 23.2% (192/826). Comparing to obese and non-obese individuals with normouricemia, individuals with hyperuricemia had significant higher values for total cholesterol, triglycerides, creatinine, and aspartate transaminase (all P < 0.05). Among non-obese individuals, hyperuricemia was associated with a lower NAFLD remission rate, compared to normouricemia (P < 0.001). However, no significant difference was observed between hyperuricemia and normouricemia among obese subjects (P > 0.05). Similar results were observed in the multivariate cox proportional hazard regression analyses. Compared to the normouricemia subjects, individuals with hyperuricemia had a significant lower likelihood of NAFLD remission (RR = 0.535, 95% CI: 0.312–0.916); and obese subjects had a significant lower likelihood of NAFLD remission than the non-obese individuals (RR = 0.635, 95% CI: 0.439–0.918). In addition, the interaction between hyperuricemia and obesity had a statistically significant effect on NAFLD remission (P = 0.048). In conclusion, hyperuricemia and obesity may be involved in NAFLD development and remission, with similar pathogenic mechanisms. Further studies are needed to confirm our findings and determine how to improve these individuals’ conditions.

Dietitian-led lifestyle modification programme for obese Chinese adolescents with non-alcoholic fatty liver disease: a randomized controlled study.

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is increasing. This study evaluated the efficacy of a dietitian-led lifestyle modification programme (D-LMP) to reduce NAFLD in obese adolescents. Subjects with intra-hepatic triglyceride content (IHTC) equal to or greater than 5% diagnosed by proton-magnetic resonance spectroscopy (1H-MRS) were enroled and randomly assigned to either the D-LMP intervention or conventional paediatrician-led consultation (P-CON) group. Subjects in the P-CON group received usual care consisting of a consultation by a paediatrician with the child and parents every 16 weeks. Intention-to-treat analysis was used for data analysis. Fifty-two subjects were recruited, with 26 in each group. After the initiation phase (at week-16), there was a greater difference in the change in the IHTC and BMI z-score in the D-LMP group (P = 0.029 and <0.001, respectively) and there was a decrease in dietary intake of fat content (P = 0.019). After 52 weeks of the maintenance phase, both groups had reductions of IHTC to 2-3% and there was no intergroup difference in the rate of reduction. During the maintenance phase, parents' involvement was minimal in the D-LMP group, with only three parents accompanying their children to attend the dietitian sessions. In contrast, over 90% of the parents in the P-CON group regularly accompanied their children to attend the consultations suggesting the possibility that regular parental and paediatrician involvement may contribute to increasing awareness on fatty liver complications. Multivariate analysis showed that only reduction in body fat remained as an independent factor associated with remission of NAFLD at the end of both study phases. A dietitian-led lifestyle modification intervention reduced IHTC, BMI z-score and body fat in obese Chinese adolescents with NAFLD. To sustain the effect of this intervention, regular parental and paediatrician involvement may be important.

Nonalcoholic fatty liver disease remission in men through regular exercise.

Recent cross-sectional and randomized controlled studies of small sample sizes revealed that regular exercise is effective for improving nonalcoholic fatty liver disease. However, there has been no large-scale longitudinal study addressing the effect of regular exercise on remission of nonalcoholic fatty liver disease. Thus, we investigated the impact of exercise on the natural history of nonalcoholic fatty liver disease. We analyzed 1,010 (860 men and 150 women) Japanese participants who received health checkups repeatedly over 10 years by a historical cohort study and were diagnosed with nonalcoholic fatty liver disease at baseline. Regular exercise was defined as participating in any kind of sports at least once a week. Nonalcoholic fatty liver disease was diagnosed by ultrasonographic images. During 10 years of follow-up, remission of nonalcoholic fatty liver disease was observed in 46.0% (396/860) of men and 48.7% (73/150) of women. In men, the adjusted hazard ratio of regular exercise for remission of nonalcoholic fatty liver disease was 1.46 (95% confidence interval 1.10–1.95, p = 0.010). However, this was not significant in women. Exercise at least once a week is implicated in the remission of nonalcoholic fatty liver disease in men.

Bariatric surgery effect on patients with nonalcoholic fatty liver disease and type II diabetes mellitus

Aims: To study the effect of sleeve gastrectomy in patients with type II diabetes mellitus and fatty liver disease. Settings and Design: This is a prospective study that was conducted from September 2016 to 2017 in KSUMC Riyadh, Saudi Arabia. Subjects and Methods: We obtained prospectively collected data from two longitudinal cohort studies at our institution. We included adults who were diagnosed with nonalcoholic fatty liver disease (NAFLD) and diabetes, with a body mass index (BMI) of >30 kg/m2, and who underwent sleeve gastrectomy. Statistical Analysis Used: Data were analyzed using JMP® 13.0.0 for data management and reporting. Continuous data were reported as means and standard deviations if normally distributed or as medians and interquartile ranges otherwise. We also used the paired t-test and Chi-square test. Results: Our population included 32 patients (mean age, 39.5 years). The preoperative and postoperative median BMIs were 42.1 and 34.2 kg/m2, respectively (P = 0.0003). The percentages of macrovascular steatosis pre- and postoperatively were 37.5 and 10, respectively (P = 0.0328). The patients who had complete diabetes mellitus (DM) remission postoperatively had a higher median BMI of 42.05 kg/m2 preoperatively and 35.7 kg/m2 postoperatively than that the patients who did not have remission (P = 0.0003). Regarding the age groups, 46.1% of patients aged 40 years who had complete diabetes remission postoperatively, which was not statistically significant. Conclusions: DM remission was statistically significant postoperatively. Remission occurred more in the higher BMI groups. There was no clear relationship between NAFLD and diabetes remission.

Probiotics administration following sleeve gastrectomy surgery: a randomized double-blind trial.

Probiotics are commonly used after bariatric surgery; however, uncertainty remains regarding their efficacy. Our aim was to compare the effect of probiotics vs placebo on hepatic, inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy (LSG). This randomized, double-blind, placebo-controlled, trial of 6-month treatment with probiotics (Bio-25; Supherb) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease (NAFLD) patients who underwent LSG surgery. The primary outcome was a reduction in liver fat content, measured by abdominal ultrasound, and secondary outcomes were improvement of fibrosis, measured by shear-wave elastography, metabolic and inflammatory parameters, anthropometrics and quality of life (QOL). Fecal samples were collected and analyzed for microbial composition. One hundred patients (60% women, mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m-2) were randomized, 80% attended the 6-month visit and 77% completed the 12-month follow-up. Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery (-0.9±0.5 vs -0.7±0.4 score; P=0.059 and 52.5 vs 40%; P=0.262, respectively) and at 12 months postsurgery. Fibrosis, liver-enzymes, C-reactive protein (CRP), leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups (P⩽0.014 for all), but not between groups (P⩾0.173 for all) at 6 and 12 months postsurgery. Within-sample microbiota diversity (alpha-diversity) increased at 6-month postsurgery compared with baseline in both study arms (P⩽0.008) and decreased again at 12 months postsurgery compared with 6 months postsurgery (P⩽0.004) but did not reach baseline values. Probiotics administration does not improve hepatic, inflammatory and clinical outcomes 6- and 12 months post-LSG.

Transient remission of nonalcoholic fatty liver disease decreases the risk of incident type 2 diabetes mellitus in Japanese men.

It is unclear how the transient remission of nonalcoholic fatty liver disease (NAFLD) affects incident type 2 diabetes mellitus (T2DM). Here, we sought to determine the effect of the transient remission of NAFLD on incident T2DM in Japanese men. We used a population-based health check-up program. The primary outcome was set as incident T2DM. We divided the participants who showed NAFLD at the time of enrollment into three groups according to their clinical course of NAFLD: the Regression group, in which the participants showed a regression of NAFLD and no relapse during the follow-up period; the Transient Remission group, in which participants achieved a transient remission of NAFLD, but had a relapse of NAFLD; and the Persistent group, in which participants showed NAFLD throughout the follow-up. The Never group of participants who did not show NAFLD throughout the follow-up served as a reference. The incidence rates of T2DM in the Never group, the Regression group, the Transient Remission group, and the Persistent group were 4.7% (62/1306), 9.2% (14/153), 18.0% (25/139), and 35.1% (120/342), respectively. In a multivariate Cox regression analysis with covariates, the adjusted hazard ratios for incident T2DM compared with the Never group were as follows: Regression group: 1.08 [95% confidence interval (CI) 0.53-2.04, P=0.81], Transient Remission group: 2.12 (95% CI 1.22-3.57, P<0.01), and Persistent group: 3.44 (95% CI 2.29-5.21, P<0.001). The adjusted hazard ratio of the Transient Remission group was significantly lower than that of the Persistent group (P<0.05). Transient remission of NAFLD significantly decreased the risk of developing T2DM.

Associations between Serum Uric Acid and the Remission of Non-Alcoholic Fatty Liver Disease in Chinese Males.

Epidemiological studies suggest that higher serum uric acid (sUA) level is significantly associated with nonalcoholic fatty liver disease (NAFLD) development. However, little information is available on the relationships between sUA and NAFLD remission. In the present study, 841 NAFLD males (30–75 years) were recruited from a Chinese prospective cohort study (PMMJS) and followed up for five years. The baseline sUA levels of participants were categorized into four quartiles: 191 μmol/L≤ sUA ≤ 347 μmol/L, 347 μmol/L < sUA ≤ 392 μmol/L, 392 μmol/L < sUA ≤ 441 μmol/L and 441 μmol/L<SUA≤676 μmol/L. As the results show, participants with elevated sUA levels at baseline were significantly associated with the decreased rate of NAFLD remission at the end of study (p<0.0001). After adjustment, RR (95%CI) for remitted NAFLD comparing Q1 to Q3 vs Q4 of sUA were 2.95 (1.49–5.83), 2.40 (1.22–4.73) and 1.39 (0.67–2.86), respectively. Furthermore, the sensitivity analysis showed these significant associations were not affected even after exclusion of participants who had hypertension, diabetes mellitus, MetS and hyperlipidemia. Additionally, the presence of the lowest quartile of sUA levels was still significantly associated with remitted NAFLD when the study population was stratified according to the smoking, and the median values of age, ALT, AST, serum creatinine, HDL-C and LDL-C. Therefore, our present study extended the previous findings and suggested that modulation of sUA levels may attenuate the progression of NAFLD.

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

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. 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. 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. The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients.

Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up

Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD's epidemiology in prospective follow-up of individuals sampled from the general population. Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.