Caspase-Cleaved Keratin 18 Measurements Identified Ongoing Liver Injury after Bariatric Surgery.

Felix Hempel,Jörn Pons-Kühnemann,Ziya Oruc,Thomas Karrasch,Lucas John Müntnich,Jens Albrecht,Andreas Schäffler,Borros Arneth,Martin Roderfeld,Harald Renz,Elke Roeb,Winfried Padberg

doi:10.3390/jcm10061233

Abstract

Bariatric surgery has emerged as an effective treatment option in morbidly obese patients with non-alcoholic fatty liver disease (NAFLD). However, worsening or new onset of non-alcoholic steatohepatitis (NASH) and fibrosis have been observed. Caspase-cleaved keratin 18 (ccK18) has been established as a marker of hepatocyte apoptosis, a key event in NASH development. Thus, ccK18 measurements might be feasible to monitor bariatric surgery patients. Clinical data and laboratory parameters were collected from 39 patients undergoing laparoscopic Roux-en-Y gastric bypass at six timepoints, prior to surgery until one year after the procedure. ccK18 levels were measured and a high-throughput analysis of serum adipokines and cytokines was carried out. Half of the cohort’s patients (20/39) presented with ccK18 levels indicative of progressed liver disease. 21% had a NAFLD-fibrosis score greater than 0.676, suggesting significant fibrosis. One year after surgery, a mean weight loss of 36.87% was achieved. Six and twelve months after surgery, ccK18 fragments were significantly reduced compared to preoperative levels (p < 0.001). Yet nine patients did not show a decline in ccK18 levels ≥ 10% within one year postoperatively, which was considered a response to treatment. While no significant differences in laboratory parameters or ccK18 could be observed, they presented with a greater expression of leptin and fibrinogen before surgery. Consecutive ccK18 measurements monitored the resolution of NAFLD and identified non-responders to bariatric surgery with ongoing liver injury. Further studies are needed to elicit the pathological mechanisms in non-responders and study the potential of adipokines as prognostic markers.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome
The present study elucidates the natural history of Caspase-cleaved keratin 18 (ccK18) levels and demonstrates its feasibility in the hepatic follow-up of a cohort undergoing Roux-en-Y gastric bypass
The high baseline levels of ccK18 and their marked decrease, following the surgery emphasize the extent of liver disease in our bariatric surgery cohort

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. It comprises a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis of the liver and complications such as hepatocellular carcinoma (HCC) [1,2]. Numerous studies have delineated the complex pathophysiological mechanisms of NAFLD in past decades, no approved drug treatment is available yet [5]. Bariatric surgery has emerged as an effective intervention in morbidly obese patients [6,7,8]. International guidelines and guidance statements recommend considering bariatric surgery, if lifestyle interventions fail [9,10,11,12]

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