Raymond Kwok

Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease – the role of transient elastography and plasma cytokeratin-18 fragments

Non‐alcoholic fatty liver disease (NAFLD) affects 15–40% of the general population. Some patients have non‐alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment.

Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study

Objective Type 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan. Design Liver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis. Results Of 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use were associated with increased CAP. Longer duration of diabetes, higher body mass index, increased ALT and spot urine albumin:creatinine ratio and lower high-density lipoprotein-cholesterol were associated with increased LSM. Ninety-four patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis and 50% had F3-4 disease. Conclusions Diabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes.

Measuring spleen stiffness to predict varices in chronic hepatitis B cirrhotic patients with or without receiving non-selective beta-blockers

we aimed to investigate the accuracy of liver (LSM) spleen stiffness measurement (SSM) with transient elastography (TE) to predict varices in the presence of non‐selective beta‐blockers (NSBB).

The accuracy of spleen stiffness measurement to predict varices in chronic hepatitis B cirrhotic patients with or without taking non‐selective beta‐blockers

we aimed to investigate the accuracy of liver (LSM) spleen stiffness measurement (SSM) with transient elastography (TE) to predict varices in the presence of non‐selective beta‐blockers (NSBB).

Prognostic Value of Controlled Attenuation Parameter by Transient Elastography

Objectives:Liver stiffness measurement (LSM) by transient elastography (TE) has been shown to predict outcomes in patients with liver disease. While controlled attenuation parameter (CAP) measurement can accurately quantify hepatic steatosis, its prognostic value is unknown. We aim to determine if CAP is predictive for liver-related events (LRE), non-hepatocellular carcinoma (HCC) cancers, and cardiovascular events (CVE).Methods:Consecutive patients with both a reliable LSM and ≥10 successful CAP measurements by TE from August 2012 to March 2016 were included in the analysis. LRE were defined as HCC or hepatic decompensation. CVE were defined as acute coronary syndrome (ACS), cerebrovascular accident (CVA), or coronary intervention (stenting or bypass).Results:Of the 5,848 patients that were examined, 4,282 (56.7% male, median age 57 years) had adequate follow-up, reliable LSM (median 6.1 kPa), and ≥10 CAP measurements (median 250 dB/m). Indications for TE were: suspected non-alcoholic fatty liver disease (NAFLD) (40.7%), hepatitis B (HBV) (37.0%), hepatitis C (2.9%), and others (19.4%). During 8,540 patient-years of follow-up, there were 45 patients with LRE (34 HCC, 33 decompensations), 73 with newly diagnosed non-HCC cancers, and 65 with CVE (27 ACS, 25 CVA, and 35 coronary interventions). CAP did not predict LRE, non-HCC cancer, or CVE on univariate analysis. On multivariate analysis, LSM, male sex, platelet count, serum albumin, and HBV etiology independently predicted LRE; age was the only independent predictor of non-HCC cancer; while age, fasting blood glucose, total cholesterol, and creatinine predicted for CVE. Subgroup analyses of viral hepatitis and NAFLD patients revealed similar results.Conclusion:Neither the presence nor the severity of hepatic steatosis as measured by CAP predict LRE, cancer, or CVE in the short term.

A new screening strategy for varices by liver and spleen stiffness measurement (LSSM) in cirrhotic patients: A randomized trial

Variceal bleeding is a common and life‐threatening complication in patients with cirrhosis. Screening with upper endoscopy is recommended but is uncomfortable to patients. Non‐invasive assessment with transient elastography for liver/spleen stiffness measurement (LSM and SSM) is accurate in detecting varices.

Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes

BACKGROUND & AIMS Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. METHODS This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. RESULTS A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). CONCLUSIONS Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. LAY SUMMARY In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.

Commentary: non-alcoholic fatty pancreas - toward an uncharted territory

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is strongly associated with insulin resistance and cardiovascular risk. 2 In obese people, ectopic fat deposition also occurs in other internal organs such as the pancreas. However, pancreatic fat is difficult to evaluate. Transabdominal ultrasonography cannot assess the pancreas adequately and is operator-dependent. Unlike the liver, pancreatic biopsy is risky and histological assessment has been limited to autopsy series, which are also problematic because of tissue necrosis after death. In their recent article, Patel et al. reported the use of chemical shift-based gradient-echo magnetic resonance imaging that measures the proton-density-fat-fraction (MRI-PDFF) to detect fatty pancreas in 43 NAFLD patients. Although MRI-PDFF is a recognised measurement of tissue fat and is likely to be accurate and reproducible, it should be highlighted that the measurement has not been correlated with pancreatic histology. As such, it is unclear at what level should pancreatic fat be considered pathological. Although it is unethical to conduct tissue studies, it is possible to test the effect of pancreatic fat on insulin resistance and b cell function. In any case, the authors provided detailed description of their radiological assessment and set the stage for future research in this important area. Interestingly, Patel et al. found an inverse association between pancreatic fat and liver fibrosis. The authors suggest that this may reflect pancreatic fibrosis as the disease advances. However, the phenomenon may also be due to patient selection. In their cohort, more patients with grade 1 steatosis had diabetes. The use of insulin sensitisers might have reduced both liver and pancreatic fat, and diabetes is the most important risk factor for liver fibrosis in NAFLD patients. Future longitudinal studies taking the influence of drugs into account will clarify this issue.

Huge Adrenal Hemangioma: A Rare Cause of Deceivingly High Liver Stiffness Measurement by Transient Elastography

ransient elastography (Fibroscan; Echosens, Paris, TFrance) is a noninvasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis and steatosis. It has become an important investigation in patients with liver diseases. Because the latest model of Fibroscan can measure controlled attenuation parameter and liver stiffness simultaneously, it may be used as a screening tool for fatty liver in high-risk individuals, eg, diabetic and obese subjects. With increasing applications of transient elastography in large cohorts of asymptomatic patients, interpretation of liver stiffness measurement (LSM) may sometimes be challenging. Grossly elevated serum alanine aminotransferase, extrahepatic cholestasis, hepatic congestion, hepatic amyloidosis, and recent food intake result in falsely high LSM and incorrect diagnosis of cirrhosis. Here we report a patient with a huge adrenal hemangioma that affected LSM. An 80-year-old man had a 10-year history of diabetic mellitus, hypertension, and hyperlipidemia. Transient elastography examination was performed in March 2014 for suspected nonalcoholic fatty liver disease. The median of 10 LSMs was 34.8 kPa, a level suggestive of cirrhosis because LSM was above 10.3 kPa. The success rate of LSM was 91%, and the interquartile range was 9.7 kPa, indicating good quality examination. As part of the work-up for probable cirrhosis, abdominal ultrasonography was performed and showed a large tumor in the right upper quadrant. Subsequent positron emission tomography–computed tomography confirmed the mass to be a large hypermetabolic, partially cystic/necrotic mass arising from the right adrenal area that measured 12.3 13.9 13.8 cm, with a maximum standardized uptake value (SUV) of 2.2 (Figures A and B). Laparotomy and right adrenalectomy were subsequently performed. Pathological features were in keeping with hemangioma with extensive degenerative changes and massive hemorrhage. A liver biopsy examination was also performed in the perioperative period, which showed no evidence of liver fibrosis (Brunt stage 0). The use of transient elastography has increased exponentially since its approval by the U. S. Food and Drug Administration on April 5, 2013. LSM correlates