Fibrogenesis marker PRO-C3 is higher in advanced liver fibrosis and improves in patients undergoing bariatric surgery

Author(s):  
Pierre Bel Lassen ◽  
Nicole Nori ◽  
Pierre Bedossa ◽  
Laurent Genser ◽  
Judith Aron-Wisnewsky ◽  
...  

Abstract Objectives Serum propeptides of type III and type VI collagen (PRO-C3 and PRO-C6) are elevated in advanced nonalcoholic fatty liver disease, but their value in patients with severe obesity and their evolution after bariatric surgery (BS) is unknown. It is unclear if these markers of fibrogenesis are affected by adipose tissue fibrosis (ATF). We studied the association of PRO-C3 and PRO-C6 with liver fibrosis before BS, examined their evolution after BS and how much patients’ ATF contribute to their levels. Methods Serum PRO-C3 and PRO-C6 were measured in 158 BS patients and compared with liver, subcutaneous and omental adipose tissue histology obtained during surgery. PRO-C3 and PRO-C6 levels of 63 patients were determined in follow-up at 3 and 12 months post BS. Results Patients in the highest quartile of PRO-C3 had a higher risk of advanced liver fibrosis (stage F3-4; odds ratio 5.8; 95% CI [1.5-29.9]; p=0.017) compared to the lowest quartile (adjustment for age, gender and BMI). PRO-C3 was positively correlated with markers of insulin resistance and liver enzymes. After BS, PRO-C3 levels decreased in patients with high baseline liver fibrosis. This decrease correlated with improvement of metabolic and liver parameters. PRO-C6 was not related to stage of liver fibrosis. ATF did not correlate with PRO-C3 or PRO-C6 levels at baseline or after BS. Conclusions PRO-C3 was associated with advanced liver fibrosis in patients with severe obesity, and decreased after BS, without being affected by ATF. These data suggest that BS prominently eliminates drivers of hepatic fibrogenesis in NAFLD.

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255535
Author(s):  
Dae-Jeong Koo ◽  
Mi Yeon Lee ◽  
Inha Jung ◽  
Sun Joon Moon ◽  
Hyemi Kwon ◽  
...  

Background and aims Fibrosis progression is the most important prognostic factor, and insulin resistance is one of the main mechanisms associated with fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD). We evaluate the association between baseline insulin resistance and future fibrosis progression in patients with NAFLD without diabetes. Approach and results This retrospective longitudinal study with 8-year follow-up period included 32,606 (men, 83%) participants aged >20 years (average age, 38.0 years) without diabetes at baseline who completed at least two comprehensive health checkups from January 1, 2010 to December 31, 2018. NAFLD was diagnosed based on ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate baseline insulin resistance. Fibrosis progression was assessed using the aspartate aminotransferase to platelet ratio index (APRI). The advanced liver fibrosis with an APRI value above the intermediate fibrosis probability (≥0.5) developed in a total of 2,897 participants during 136,108 person-years. 114 participants progressed to a high fibrosis probability stage (APRI >1.5) during 141,064 person-years. Using the lowest baseline HOMA-IR quartile group (Q1) as a reference, the multivariate-adjusted hazard ratio (HR) for development of advanced liver fibrosis (APRI ≥0.5) in the highest baseline HOMA-IR quartile group (Q4) was 1.95 (95% confidence interval [CI] 1.74–2.19; Model 4). And the HR for development of advanced liver fibrosis with high fibrosis probability was 1.95 (95% CI 1.10–3.46; Model 4). The positive association was maintained throughout the entire follow-up period. The baseline HOMA-IR model was superior to the baseline body mass index (BMI) model in predicting the progression of fibrosis probability. Conclusions In this longitudinal study, we found that the degree of baseline insulin resistance, assessed by HOMA-IR values, was positively associated with future fibrosis progression in patients with NAFLD without diabetes.


Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 132
Author(s):  
Kenichiro Murayama ◽  
Michiaki Okada ◽  
Kenichi Tanaka ◽  
Chika Inadomi ◽  
Wataru Yoshioka ◽  
...  

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.


2021 ◽  
Author(s):  
Arnaud Liagre ◽  
Francesco Martini ◽  
Radwan Kassir ◽  
Gildas Juglard ◽  
Celine Hamid ◽  
...  

Abstract Purpose The treatment of people with severe obesity and BMI > 50 kg/m2 is challenging. The present study aims to evaluate the short and mid-term outcomes of one anastomosis gastric bypass (OAGB) with a biliopancreatic limb of 150 cm as a primary bariatric procedure to treat those people in a referral center for bariatric surgery. Material and Methods Data of patients who underwent OAGB for severe obesity with BMI > 50 kg/m2 between 2010 and 2017 were collected prospectively and analyzed retrospectively. Follow-up comprised clinical and biochemical assessment at 1, 3, 6, 12, 18, and 24 months postoperatively, and once a year thereafter. Results Overall, 245 patients underwent OAGB. Postoperative mortality was null, and early morbidity was observed in 14 (5.7%) patients. At 24 months, the percentage total weight loss (%TWL) was 43.2 ± 9, and percentage excess weight loss (%EWL) was 80 ± 15.7 (184 patients). At 60 months, %TWL was 41.9 ± 10.2, and %EWL was 78.1 ± 18.3 (79 patients). Conversion to Roux-en-Y gastric bypass was needed in three (1.2%) patients for reflux resistant to medical treatment. Six patients (2.4%) had reoperation for an internal hernia during follow-up. Anastomotic ulcers occurred in three (1.2%) patients. Only two patients (0.8%) underwent a second bariatric surgery for insufficient weight loss. Conclusion OAGB with a biliopancreatic limb of 150 cm is feasible and associated with sustained weight loss in the treatment of severe obesity with BMI > 50 kg/m2. Further randomized studies are needed to compare OAGB with other bariatric procedures in this setting. Graphical abstract


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael W Foster ◽  
Sara E Badenhausen ◽  
Colleen Tewksbury ◽  
Noel N Williams ◽  
J Eduardo Rame ◽  
...  

Introduction: Heart failure patients with severe obesity endure significant morbidity and frequent hospitalizations. Bariatric surgery is proven to provide durable weight loss for those with severe obesity, but the clinical impact and safety of these procedures among patients with heart failure has not been well-demonstrated. Methods: We conducted a medical record query of patients who have a previous diagnosis of heart failure (HFpEF and HFrEF) and underwent subsequent Roux-En-Y gastric bypass or laparoscopic sleeve gastrectomy at a high-volume metabolic and bariatric surgery center. We compared clinical, demographic, and echocardiographic data captured just prior to the bariatric procedure to the most recent data available in the medical record for each patient. Results: There were 50 patients (88% had HFpEF) included in this study. Time from HF diagnosis to most recent follow-up ranged from 0.2 to 20.3 years (median 6.7 years) and there was no recorded mortality. The median time from HF diagnosis to surgery was 2.3 years and median time from surgery to recent follow-up was 2.9 years. Post-operative median decrease in BMI was 8.8 kg/m 2 , HF hospitalizations were 0.4 per patient year (PPY) to 0.15 PPY, p=0.008, and median NYHA Class was II pre-op and I post-op, p=0.048). LVEF, LVESD, and LVEDD were not significantly changed post-operatively (Table 1). Conclusion: Weight loss following bariatric surgery for patients with HF led to improvements in NYHA Class, fewer hospitalizations for HF, and was not associated with perioperative mortality. It is reasonable to consider bariatric surgery for this patient population, but further prospective investigation is warranted.


2020 ◽  
Vol 30 (11) ◽  
pp. 4359-4365 ◽  
Author(s):  
Aashir Kaul ◽  
Vitish Singla ◽  
Aditya Baksi ◽  
Sandeep Aggarwal ◽  
Amit Bhambri ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S207-S208
Author(s):  
V Domislović ◽  
I Knežević-Štromar ◽  
M Premužić ◽  
M Brinar ◽  
D Vranešić Bender ◽  
...  

Abstract Background Patients with IBD are at higher risk for non-alcoholic fatty liver disease (NAFLD) comparing to general population. Complex pathogenesis of NAFLD in IBD may be related to disease-specific risk factors such as chronic inflammation, steroid exposure, drug induced hepatotoxicity, malnutrition and alteration of gut microbiota, which is emerging as a major factor in the pathogenesis of NAFLD. The goal of the study was to investigate factors associated with NADLF and advanced liver fibrosis (ALF) in patients with CD and UC. Methods This is a retrospective study on IBD patients without extraintestinal manifestations and known liver disease. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥ 36, and ALF was defined as FIB-4 ≥ 2.67. Predictors of NAFLD development were analysed using Kaplan–Meier and Cox regression analyses. Results In this retrospective study, we have included 225 IBD patients; 72.4% (n = 163) patients with CD and 27.6% (n = 62) patients with UC (median age 41.2 yr, 53.7% males) which were observed for a median of 4.6 years. There were 63.1% (n = 142) patients with normal BMI, 27.6% (n = 62) overweight and 9.3% (n = 21) obese patients. Obese patients had the highest HIS score 43.9 ± 5.9, following with overweight 37.8 ± 5.7 and normal BMI 30 ± 4.3 kg/m2, p &lt; 0.001. During the follow-up obese and overweight patients had higher risk of developing NAFLD comparing to patients with normal BMI (obese HR = 11.1 95% CI 4.3–28.3 and overweight HR = 5.55 95% CI 3.4–9.1, Logrank test p &lt; 0.001) (Figure 1). Regarding FIB-4 score there, was no difference among different BMI categories (p = 0.192), and there was no difference in ALF development in the follow-up period (Logrank test p = 0.91). In Cox proportional-hazards regression significant predictors for NAFLD development were dyslipidaemia HR=2.11, 95% CI 1.2–3.7, overweight HR=6 95% CI 3.6–10, and obesity HR=13.4, 95% CI 7–35. Conclusion NAFLD is frequent comorbidity in patients with CD and UC, which can lead to development of advanced liver fibrosis. Our results show that patients with IBD have a high risk of NAFLD development, whereas the increased risk for ALF was not observed. Overweight and obese patients and those with dyslipidemia should be closer monitored due to significantly higher risk of NAFLD. This study points out the complexity disease-specific risk factors and importance of better stratifying IBD patients at risk of NAFLD and advanced liver fibrosis.


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