Non‐alcoholic fatty liver disease: a review of epidemiology,risk factors,diagnosis and management

Due to the rising prevalence of obesity and type II diabetes mellitus, non‐alcoholic fatty liver disease is becoming the leading cause of chronic liver disease in the Western world. In some patients, simple steatosis can result in non‐alcoholic steatohepatitis which over time can lead to liver cirrhosis and its associated sequelae, including hepatocellular carcinoma. Early identification and management of patients at risk with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. In this review, we will discuss the epidemiology of non‐alcoholic fatty liver disease, pathogenesis, diagnosis, management and surveillance strategies to offset the morbidity and mortality of this disease, as well as liver and non‐liver‐related complications.     

Transitional features of histologic type of non-alcoholic fatty liver disease in Korean young men

Background and Aim: The prevalence of non‐alcoholic fatty liver disease (NAFLD) is increasing in Korea as the dietary pattern and lifestyle become more Westernized and the obese population increases. The spectrum of NAFLD ranges from asymptomatic steatosis to non‐alcoholic steatohepatitis (NASH) and cirrhosis. Schwimmer et al. divided NASH into three types according to the histological characteristics, such as adult type, pediatric type and overlap type. We investigated clinical and histologic features of NAFLD patients in Korean young men. Methods: A total of 64 male patients under age 30 years, diagnosed as NAFLD by a liver biopsy, were reviewed retrospectively. NASH was diagnosed by NAFLD activity score (NAS), and NASH patients were classified with Schwimmer's histological classification. Results: Pathological features of liver biopsy revealed NASH in most cases (59 cases, 92.2%) including 29 cases (45.3%) of borderline NASH and 30 cases (46.9%) of definite NASH. The definite NASH group showed significantly high aspartate aminotransferase/alanine aminotransferase levels compared to the borderline NASH group. There were four cases (6.8%) of pediatric type, 17 cases (28.8%) of adult type, and 38 cases (64.4%) of overlap type in the NASH group. NAS was 3.75 ± 0.05 in the pediatric type, 4.29 ± 1.16 in the adult type and 4.87 ± 1.21 in the overlap type, and the overlap type showed a higher NAS than the pediatric type. The fibrosis stage was significantly higher in the overlap type than the other types. Conclusion: Most Korean young men with NAFLD turned out to have borderline or definite NASH. More than half of the NASH cases showed overlap type in Korean young men.     

Case report of diet‐related improvements of non‐alcoholic steatohepatitis evaluated by four consecutive liver biopsies

We report the case of a 46‐year‐old man who achieved remarkable improvement of characteristic non‐alcoholic steatohepatitis by dieting. Initially, his body mass index was 40.7 kg/m². He proactively commenced a low calorie diet and his body mass index decreased to 28 kg/m² after 4 years. During the same period, we carried out liver biopsy four times. Liver fibrosis as well as inflammation, steatosis and ballooning improved, and the non‐alcoholic fatty liver disease activity score decreased from 4 to 0. The fat deposits of liver tissue changed from macrovesicular droplets to microvesicular, and finally disappeared. Along with improved histology, alanine aminotransferase, homeostasis model assessment‐insulin resistance, ferritin, leptin, high‐sensitivity C‐reactive protein and cytokeratin 18 decreased, and adiponectin increased linearly. However, no clear changes were observed in markers for Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA⁺M2BP), type IV collagen 7S, procollage III peptide and fibrosis‐4 index along with dieting. This is the first study to report gradual improvement of liver histology during four liver biopsies and fibrosis markers in a patient with non‐alcoholic steatohepatitis who achieved complete recovery solely by dieting.     

LAPAROSCOPIC FEATURES AND INTEROBSERVER VARIATION OF HISTOLOGICAL DIAGNOSIS IN PATIENTS WITH NON‐ALCOHOLIC FATTY LIVER DISEASE

Background: There is a lack of information regarding the laparoscopic features and interobserver variation of histological diagnosis in patients with non‐alcoholic fatty liver disease (NAFLD). Methods: Thirty‐five patients with NAFLD were studied for laparoscopic and histological findings. For the study of interobserver variation of histological diagnosis, two pathologists from different hospitals independently observed the 35 liver samples with patient names blinded to the pathologists. Assessment of laparoscopic findings on the diagnosis of non‐alcoholic steatohepatitis (NASH) was also investigated. Results: Histological diagnoses of the two pathologists were identical in 28 (five fatty liver, 23 NASH) patients, whereas they were not identical in seven patients (20%). The difference of diagnosis was mainly caused by the difference of judgment of minimal fibrosis and minimal necroinflammatory grade. Analysis of the laparoscopic findings revealed that small regular depressions were frequently found on the liver surface in patients with NASH. Scatter of dye on the liver surface facilitated the observation of this finding. Sensitivity and specificity of small depressions in the diagnosis of NASH was 73.9% and 80.0%, respectively. Conclusion: Interobserver variation of the diagnosis was found in 20% of patients with NAFLD. Small regular depressions were characteristic findings of NASH. Laparoscopy is assessed to be useful for diagnosis of NAFLD, especially of early stage of NASH.     

Efficacy of ezetimibe for the treatment of non‐alcoholic steatohepatitis: An open‐label,pilot study

Aim: Non‐alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations. Methods: We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50–60%, fat 20–30%, protein 15–20%) and exercise counseling from 3 months before the ezetimibe treatment. Results: The serum aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transpeptidase, low‐density lipoprotein cholesterol, high‐sensitivity C‐reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow‐up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage. Conclusion: Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large‐scale clinical trial in the future.     

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.     

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is closely associated with metabolic syndrome. The alarming epidemics of diabetes and obesity have fueled an increasing prevalence of NAFLD, particularly among these high-risk groups. Histologically, NAFLD encompasses a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis on liver biopsy. Non-alcoholic steatohepatitis can progress to cirrhosis in a fraction of patients. There is currently little understanding of risk factors for disease progression and the disease pathogenesis has not been fully defined. Liver biopsy remains the gold standard for diagnosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. There are no well-established pharmacological agents for treatment of NASH, although this is a subject of ongoing research.