The efficacy of multi-disciplinary lifestyle modifications in Taiwanese nonalcoholic steatohepatitis patients.

Lifestyle modification is the standard of care for nonalcoholic fatty liver disease (NAFLD) patients. We aimed to investigate the efficacy of a short-term lifestyle modification program in the disease course of Taiwanese nonalcoholic steatohepatitis (NASH) patients with paired biopsies. All patients received a 6-month, strict multidisciplinary program of lifestyle modifications led by physicians, dieticians, and nursing staff. The histopathological and clinical features were assessed. The endpoints were normalization of transaminase levels, metabolic parameters, a decrease in the NAFLD activity score (NAS) ≥1, and a decrease in the fibrosis stage ≥1. We also aimed to elucidate the predictors associated with disease progression. A total of 37 patients with biopsy-proven NASH were enrolled. The normalization of transaminase levels increased from 0% to 13.5%. There were also significantly increased proportions of patients with normal total cholesterol, triglyceride, and hemoglobin A1c levels. Fifteen (40.5%) patients had an increased NAS ≥1, whereas 10 (27.0%) patients had NAS regression. Twelve (32.4%) patients had increased fibrosis ≥1 stage. Only 2 (5.4%) patients experienced fibrosis regression. A high fasting plasma glucose (FPG) level was associated with NAS progression. Older age and higher transaminase and FPG levels were factors associated with fibrosis progression. Seven (18.9%) patients achieved a body weight reduction >3%, and 4 (57.1%) of them experienced NAS regression. No significant effect of weight reduction on the progression of fibrosis was observed. The short-term lifestyle modification program significantly decreased liver enzymes and metabolic parameters in NASH patients. A more precise or intensive program may be needed for fibrosis improvement.

Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma.

Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

Community-centered Disease Severity Assessment of Metabolic Dysfunction-associated Fatty Liver Disease.

Background and Aims: Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease (MAFLD) remains elusive. This study assessed the fibrosis stages and features of MAFLD between different items. We also aimed to investigate the associations between advanced fibrosis and risk factors. Methods: This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community. Patients were stratified following MAFLD diagnostic criteria, to group A (395 patients) for type 2 diabetes, group B (1,818 patients) for body mass index (BMI)>23 kg/m2, and group C (44 patients) for BMI≤23 kg/m2 with at least two metabolic factors. Advanced fibrosis was defined as a fibrosis-4 index>2.67. Results: Between 2009 and 2020, 1,948 MAFLD patients were recruited, including 478 with concomitant liver diseases. Advanced fibrosis was observed in 125 patients. A significantly larger proportion of patients in group C (25.0%) than in group A (7.6%) and group B (5.8%) had advanced fibrosis (p<0.01). Logistic regression analysis found that hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection (odds ratio [OR]: 12.14, 95% confidence interval [CI]: 4.04-36.52; p<0.01), HCV infection (OR: 7.87, 95% CI: 4.78-12.97; p<0.01), group C (OR: 6.00, 95% CI: 2.53-14.22; p<0.01), and TC/LDL-C (OR: 1.21, 95% CI: 1.06-1.38; p<0.01) were significant predictors of advanced fibrosis. Conclusions: A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis. HCV infection was significantly associated with advanced fibrosis.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein expression predicts disease severity in nonalcoholic steatohepatitis patients.

The role of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) in the prediction of disease severity in nonalcoholic fatty liver disease (NAFLD) remains elusive. This study evaluated the performance of WFA+ -M2BP in predicting fibrosis in patients with NAFLD. A total of 80 patients with biopsy-proven nonalcoholic steatohepatitis (NASH) were enrolled. Serum WFA+ -M2BP levels were measured using standard methods. The fibrosis-4 (FIB-4) index was also measured. The mean values of WFA+ -M2BP were 1.0, 1.0, 0.8, and 2.2 in Metavir fibrosis stage F0, F1, F2, and F3-4, respectively (linear trend p = 0.005). The optimal cut-off value of WFA+ -M2BP in predicting advanced fibrosis (F3-4) was 1.37 cut-off index (COI), yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of 75.0, 79.4, 39.1, 94.7, and 78.7%, respectively (p < 0.001). Combining WFA+ -M2BP with FIB-4 significantly increased the diagnostic performance for advanced fibrosis, yielding specificity, PPV, and accuracy of 100, 100, and 93%, respectively. The significant factors predicting advanced liver fibrosis in the multivariate regression analysis were WFA+ -M2BP ≥ 1.37 COI (OR/confidence interval [CI]: 9.49/1.63-55.21, p = 0.01) and FIB-4 ≥ 2.80 (OR/CI: 38.18/4.89-297.93, p = 0.001). Monitoring WFA+ -M2BP is suitable for noninvasive assessment of liver fibrosis in NASH patients, particularly in combination with FIB-4.

First-in-Asian double-blind randomized trial to assess the efficacy and safety of insulin sensitizer in nonalcoholic steatohepatitis patients.

BACKGROUND: The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. AIMS: The double-blind, randomized, placebo-controlled trial was conducted aiming to investigate the efficacy and safety of pioglitazone in NASH patients. METHODS: A total of 90 NASH patients (66 males, age = 44.1 ± 12.7 years) were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. The primary endpoint was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening was also evaluated. RESULTS: At EOT, there was a significantly decline of alanine aminotransferase (86.9 ± 34.3 to 45.7 ± 35.8 IU/L, p = 0.003) level in Arm A patients. In intention-to-treat analysis among 66 patients who completed paired biopsies, The NAFLD activity score (NAS) of 30 Arm A patients significantly decreased from 4.27 ± 1.14 at baseline to 2.53 ± 1.63 at EOT (p < 0.0001), whereas there was no significant change in patients of Arm B (3.94 ± 1.41 vs 3.94 ± 1.51, p = 1.0). NASH improvement without worsening of fibrosis was achieved in 46.7% (14/30) patients in Arm A, compared to 11.1% (4/36) patients in Arm B (p = 0.002). Liver fat content reduced (20.2 ± 9.0 to 14.3 ± 6.9%, p < 0.0001) on MRI-PDFF in Arm A compared to their counterparts. No significant difference of adverse events occurred between groups. CONCLUSIONS: A 24-week pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444).