Clinical usage of serum ferritin to assess liver fibrosis in patients with non‐alcoholic fatty liver disease: Proceed with caution

Serum ferritin was recently reported to have low diagnostic accuracy for the detection of advanced fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). To corroborate these findings, we investigated the diagnostic accuracy of serum ferritin levels for detecting liver fibrosis in NAFLD patients utilizing a large Japanese cohort database. A total 1201 biopsy‐proven NAFLD patients, seen between 2001 and 2013, were enrolled into the Japan Study Group of NAFLD. Analysis was performed on data from this cohort comparing between serum ferritin levels and hepatic histology. Serum ferritin increased with increasing histological grade of steatosis, lobular inflammation and ballooning. Multivariate analyses revealed that sex differences, steatotic grade and fibrotic stage were independently associated with serum ferritin levels (P < 0.0001, <0.0001, 0.0248, respectively). However, statistical analyses performed using serum ferritin levels demonstrated that the area under the receiver–operator curve for detecting fibrosis was not adequate for rigorous prediction. Several factors including sex differences, steatosis and fibrosis were found to correlate with serum ferritin levels. Therefore, serum ferritin may have low diagnostic accuracy for specifically detecting liver fibrosis in NAFLD patients due to the involvement of multiple hepatocellular processes.     

Association of recently described adipokines with liver histology in biopsy‐proven non‐alcoholic fatty liver disease: a systematic review

The prevalence of non‐alcoholic fatty liver disease (NAFLD) is rising, as is the prevalence of obesity and type 2 diabetes. It is increasingly recognized that an impaired pattern in adipokine secretion could play a pivotal role in the development of NAFLD. We performed a systematic review to evaluate the potential link between newly described adipokines and liver histology in biopsy‐proven NAFLD patients. A computerized literature search was performed in PubMed, EMBASE and Web of Science electronic databases. Thirty‐one cross‐sectional studies were included, resulting in a total of seven different investigated adipokines. Studies included in this review mainly had a good methodological quality. Most adipokines were suggested to be involved in the inflammatory response that develops within the context of NAFLD, either at hepatic or systemic level, and/or hepatic insulin resistance. Based on literature, clinical studies suggest that chemerin, resistin and adipocyte‐fatty‐acid‐binding protein potentially are involved in NAFLD pathogenesis and/or progression. However, major inconsistency still exists, and there is a high need for larger studies, together with the need of standardized assays to determine adipokine levels.     

Paediatric non‐alcoholic fatty liver disease: an overview

Non‐alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non‐alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non‐hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research.     

Systematic review and meta‐analysis to determine the impact of iron depletion in dysmetabolic iron overload syndrome and non‐alcoholic fatty liver disease

Aims

Iron reduction has been proposed as treatment for dysmetabolic iron overload syndrome (DIOS) and non‐alcoholic fatty liver disease (NAFLD), but results of published trials are conflicting. We undertook a systematic review and meta‐analysis to determine the impact of phlebotomy in DIOS and NAFLD.

Methods

We searched multiple databases systematically for studies evaluating the impact of phlebotomy in DIOS and NAFLD. We calculated weighted summary estimates using the inverse variance method. Study quality was assessed using the Cochrane collaboration tool.

Results

We identified nine studies with 820 patients (427 had phlebotomy, 393 lifestyle changes alone). Iron depletion did not improve the Homeostasis Model Assessment (HOMA) index (mean difference [MD] ?0.6; confidence interval (CI), ?1.7, 0.5; P = 0.3), insulin level (MD ?0.8 mU/L; CI, ?5.3, 3.7; P = 0.73), or aspartate aminotransferase (AST) (MD ?0.7 IU/L; CI, ?3.2, 1.8; P = 0.6) in DIOS and/or NAFLD patients as compared to lifestyle changes alone (five studies, 626 patients). There was mild improvement in alanine aminotransferase (ALT) (MD ?6.6 IU/L; CI, ?11, ?2.1); P < 0.01), but the effect size was very small (Cohen's d, 0.15; r statistic, 0.07). Even in the subgroup of patients with NAFLD and hyperferritinemia, phlebotomy did not improve the HOMA index, insulin level, ALT, or AST. Additionally, no study showed significant improvement in liver inflammation or fibrosis with iron reduction.

Conclusions

Phlebotomy does not bring about significant improvement in indices of insulin resistance, liver enzymes, or liver histology in patients with DIOS and/or NAFLD compared to lifestyle changes alone. Current evidence does not support the use of phlebotomy in patients with DIOS or NAFLD.

     

Relationship of non‐alcoholic fatty liver disease to colorectal adenomatous polyps

Background and Aims: Metabolic syndrome and insulin resistance are associated with a higher risk of colon cancer. Non‐alcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome in the liver. This investigation was initiated to determine whether NAFLD has a relationship to colorectal adenomatous polyps. Methods: We examined the 2917 participants who underwent a routine colonoscopy at Kangbuk Samsung Hospital in 2007. We divided the 2917 subjects into the adenomatous polyp group (n = 556) and the normal group (n = 2361). Anthropometric measurements, biochemical tests for liver and metabolic function, and abdominal ultrasonographs were assessed. Results: The prevalence of NAFLD was 41.5% in the adenomatous polyp group and 30.2% in the control group. By multiple logistic regression analysis, NAFLD was found to be associated with an increased risk of colorectal adenomatous polyps (odds ratio, 1.28; 95% confidence interval, 1.03–1.60). An increased risk for NAFLD was more evident in patients with a greater number of adenomatous polyps. Conclusion: NAFLD was associated with colorectal adenomatous polyps. Further studies are needed to confirm whether NAFLD is a predictor for the development of colorectal adenomatous polyps and cancer.     

Relationship of serum uric acid level with non‐alcoholic fatty liver disease and its inflammation progression in non‐obese adults

Aim

This study aimed to evaluate the relationship between serum uric acid (SUA) level and non‐alcoholic fatty liver disease (NAFLD) in non‐obese adults.

Methods

A cross‐sectional study was carried out among 4098 adults, including 1936 non‐obese and 2162 obese individuals. An additional 93 non‐obese adults with biopsy‐proven NAFLD were also included.

Results

The overall prevalence of NAFLD was 39.51% in the study group, and 14.88% in non‐obese adults. The NAFLD patients had significantly higher SUA levels than controls in both men and women. The non‐obese group had a higher NAFLD risk with increased SUA levels than the obese group, with odd ratios (95% confidence interval) of 2.559 (1.870–3.503) and 1.692 (1.371–2.087), respectively. In 93 non‐obese adults with biopsy‐proven NAFLD, SUA levels were significantly higher in those with non‐alcoholic steatohepatitis. The prevalence of non‐alcoholic steatohepatitis and lobule inflammation tended to increase to 57.58% and 66.67% as the SUA level increased to the fourth quartile. Subjects with hyperuricemia had significantly higher NAFLD activity scores and more serious lobule inflammation than the normal group.

Conclusion

Non‐obese adults have higher NAFLD risk with increased SUA levels than obese individuals, and the inflammation progression of NAFLD is associated with increased SUA level in non‐obese subjects.