The Steatosis-Associated Fibrosis Estimator (SAFE) score for assessing significant liver fibrosis in patients with psoriasis.

BACKGROUND: There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis. OBJECTIVES: To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference. METHODS: We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did. CONCLUSIONS: The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice.

Familial clustering of nonalcoholic fatty liver disease in first-degree relatives of adults with lean nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: The heritability of nonalcoholic fatty liver disease (NAFLD) in lean individuals is undetermined. This familial aggregation study aimed to evaluate familial linkage for NAFLD and the risk of NAFLD among first-degree relatives of probands with lean NAFLD. METHODS: This study prospectively recruited cohorts of probands with lean NAFLD, probands with obese NAFLD, and lean probands with non-NAFLD and their respective first-degree relatives. A total of 257 participants were evaluated for liver steatosis, defined by the controlled attenuation parameter ≥288 dB/m2 , metabolic characteristics, and the PNPLA3, TM6SF2, and MBOAT7 polymorphisms. RESULTS: The prevalence of NAFLD in first-degree relatives of lean NAFLD probands (39.9%) was similar to that in the obese NAFLD group (36.9%) and was significantly higher than in lean persons without NAFLD (19.1%). First-degree relatives of probands with NAFLD who were male, and had central obesity, hypertriglyceridaemia, insulin resistance, and the PNPLA3 rs738409C>G allele had a significantly higher prevalence of NAFLD. After multivariable adjustment for gender, metabolic characteristics, and the PNPLA3 rs738409C>G allele, first-degree relatives of probands with lean NAFLD (odds ratio [OR], 5.13; 95% CI, 1.77-14.86) and obese NAFLD (OR, 3.20; 95% CI, 1.14-8.99) exhibited an increased risk of NAFLD compared with those of lean controls without NAFLD. CONCLUSIONS: Our well-phenotype cohorts revealed familial clustering of NAFLD and higher risks of NAFLD in first-degree relatives of probands with lean or obese NAFLD. The findings encourage clinicians caring for NAFLD patients to be more vigilant for NAFLD in their family members.

Effect of a 12-week home-based exercise training program on aerobic capacity, muscle mass, liver and spleen stiffness, and quality of life in cirrhotic patients: a randomized controlled clinical trial.

BACKGROUND: Physical inactivity and sarcopenia are two important predictors associated with increased morbidity and mortality in patients with cirrhosis. At present, the benefit of a home-based exercise training program is not well established in cirrhotic patients. The main objective of this study was to evaluate the effect of a 12-week home-based exercise training program on aerobic capacity in cirrhotic patients. METHODS: This is a randomized controlled study. Patients with compensated cirrhosis were randomized by a block of 4 with concealed allocation to the home-based exercise training (n = 20) or control (n = 20). Both groups received protein supplementation (9 g/day) for 12 weeks. The home-based exercise training program included several aerobic/isotonic moderate-intensity continuous training exercises for 40 min per session, at least four times a week, with a total duration of 12 weeks. The heart rate was continuously monitored using a Garmin® watch. In the control group, patients received exercise instruction without active encouragement and continuous monitoring. The primary outcome was a change in the 6-min walk test from baseline. Secondary outcomes were the difference in thigh muscle thickness, liver stiffness, spleen stiffness, and quality of life. RESULTS: A total of 40 patients were enrolled prospectively. The mean age was 56.3 ± 7.8 years, with a male predominance of 65%. The mean body mass index was 25.23 ± 3.0 kg/m2, and all were Child-Pugh A. Chronic hepatitis B or C was the primary cause of cirrhosis. The baseline values were a 6-min walk test of 475 ± 70 m, liver stiffness of 15.3 ± 9.3 kPa, spleen stiffness of 29.8 ± 21.7 kPa, and thigh muscle thickness (average compression index) of 0.64 ± 0.2 cm/m2. All baseline characteristics between the two groups were not different except the mean muscle mass which was significantly higher in the home-based exercise training group (p = 0.03, 95% CI 0.01 to 0.17). At the end of the study, no significant difference in the 6-min walk test was observed (p = 0.36, 95% CI -15.5 to 41.7). Liver stiffness measurement significantly improved in both groups, but no significant difference between groups was demonstrated (p = 0.77, 95% CI -1.3 to 1.8). Thigh muscle thickness was not different between groups. The fatigue domain of the quality of life index was significantly improved in the home-based exercise training group compared with the control group (p = 0.05, 95% CI 0.00 to 0.67). No adverse events occurred in a home-based exercise training program. CONCLUSIONS: A 12-week moderate-intensity home-based exercise training program in compensated cirrhotic patients significantly improved the fatigue domain of the quality of life index without an increase in adverse events. However, no benefit in terms of aerobic capacity, thigh muscle mass, liver stiffness, and spleen stiffness was demonstrated. TRIAL REGISTRATION: Thai Clinical Trials Registry number TCTR20190926002, 26/09/2019 (Retrospectively registered).

Dietary Composition and Its Association with Newly Diagnosed Nonalcoholic Fatty Liver Disease and Insulin Resistance.

Dietary modification is essential for treating nonalcoholic fatty liver disease (NAFLD); however, the dietary components are less well defined. We enrolled 252 adults with no history of liver disease and excessive alcohol use to evaluate the relationship between macronutrients and NAFLD and insulin resistance. Participants took photographs of their meals and documented their food intake in a food diary for seven consecutive days. A dietitian estimated the type and portion size of food items and analyzed nutrients with INMUCAL-Nutrients software. Later, participants underwent transient elastography to diagnose NAFLD and blood tests to measure insulin resistance using the homeostasis model. Total energy intake and the proportion of carbohydrate, fat, and protein consumption did not differ between participants with NAFLD (n = 41) and those without NAFLD (n = 211). Using multiple logistic regression analysis, daily intake of protein < 1.0 g/kg (OR: 3.66, 95% CI: 1.41-9.52) and full-fat dairy product ≥ 50 g (OR: 0.42, 95% CI: 0.18-0.99) were associated with NAFLD. Insulin resistance was associated with a daily intake of protein < 1.0 g/kg (OR: 3.09, 95% CI: 1.59-6.05), full-fat dairy product ≥ 50 g (OR: 0.46, 95% CI: 0.25-0.82), and dietary fiber ≥ 8 g (OR: 0.41, 95% CI: 0.22-0.74). Our data show that a low protein intake increases the odds for NAFLD and insulin resistance. Contrarily, a high intake of full-fat dairy products and dietary fiber has been associated with a potential protective effect against NAFLD and insulin resistance.

Moderate-Intensity Aerobic vs Resistance Exercise and Dietary Modification in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial.

INTRODUCTION: This randomized trial aimed to compare the effects of moderate-intensity aerobic vs resistance exercise with dietary modification in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients with NAFLD were randomly assigned (1:1) to a 12-week supervised training program of moderate-intensity aerobic or resistance exercise with dietary intervention consisting of monthly individual nutritional counseling by a dietician. Transient elastography, anthropometry, body composition, cardiorespiratory fitness, biochemistries, and glucose tolerance were measured at baseline and 12 weeks. RESULTS: Eighteen subjects exercised for an average of 3.35 ± 0.30 sessions a week in the aerobic group, and 17 subjects exercised an average of 3.39 ± 0.28 sessions a week in the resistance group. After completion of the training program, hepatic fat content was similarly reduced in both groups (P < 0.001). The mean relative reduction from baseline in the aerobic group was -10.3% (95% confidence interval -18.2 to -2.40) and the resistance group was -12.6% (-20.5 to -4.69). Liver steatosis (defined as controlled attenuation parameter >248 dB/m) disappeared in 9 (50%) of the aerobic group and in 9 (53%) of the resistance group. Whole-body and muscle insulin sensitivity indexes were improved, and waist circumference was reduced comparably in both exercise groups. The number of exercise sessions per week was correlated with the absolute reduction in hepatic fat content (r = 0.52; P = 0.001). Weekly exercise training ≥3 sessions substantially attenuates liver fat accumulation independent of weight loss. DISCUSSION: Moderate-intensity aerobic training and resistance training with dietary modification are equally effective for reducing intrahepatic fat and improving underlying insulin resistance among patients with NAFLD.

The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response.

BACKGROUND & AIMS: The clinical significance of steatohepatitis in chronic hepatitis B remains unclear. This study aimed to determine the prevalence and risk factors for steatohepatitis in chronic hepatitis B, and to determine its correlation with liver fibrosis and response to antiviral therapy. METHODS: Liver histopathology of 256 consecutive chronic hepatitis B patients with serum hepatitis B virus DNA >2000 IU/mL were analysed with clinical and laboratory characteristics. Virological and biochemical responses were prospectively assessed in the 112 patients treated with antiviral monotherapy. RESULTS: Hepatic steatosis was observed in 38% of the entire cohort, and steatohepatitis was diagnosed in 18% of patients with hepatic steatosis according to Brunt's classification. The presence of steatohepatitis was associated with overweight/obese (odds ratio, 5.99; 95% CI, 1.32-27.2) and hypertriglyceridaemia (odds ratio, 2.95; 95% CI, 1.07-8.15). None of the viral characteristics including HBeAg status, genotypes and viraemia levels was associated with the presence of steatohepatitis. Steatohepatitis was an independent predictor of significant fibrosis (odds ratio, 10.0; 95% CI, 2.08-48.5) and advanced fibrosis (odds ratio, 3.45; 95% CI, 1.11-10.7) after adjusting for viraemia levels and features of the metabolic syndrome. The rates of suppression of serum hepatitis B virus DNA <20 IU/mL combined with aminotransferase normalization at week 48 of antiviral therapy were not different between the steatohepatitis and non-steatohepatitis groups (43% vs 53%; P=.475). CONCLUSIONS: Steatohepatitis is not uncommon in chronic hepatitis B patients. It is associated with metabolic syndrome but not viral factor. This study demonstrates that steatohepatitis is related to the severity of liver fibrosis but it does not affect response to antiviral therapy.

Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B.

AIM: To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients. METHODS: Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA >2000 IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy. RESULTS: Using ALT <40 IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19 999, 20 000-199 999, and ≥200 000 IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflammation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA <20 000 IU/mL, liver biopsy could be avoided in 88% when LSM <7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA ≥20 000 IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM ≥7 kPa is used as a predictor of significant pathological lesions. CONCLUSION: The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these non-invasive measures is proposed with liver biopsy being pursued in selected cases.