Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of non-alcoholic steatohepatitis (NASH) and fibrosis identifies an at-risk group with increased risk of cardiovascular and liver-related deaths. The identification and management of this at-risk group remains a clinical challenge. \ud \ud Aim: To perform a systematic review of the established and emerging strategies for the diagnosis and staging of NAFLD. \ud \ud Methods: Relevant research and review articles were identified by searching PubMed, MEDLINE and EMBASE. \ud Results: There has been a substantial development of non-invasive risk scores, biomarker panels and radiological modalities to identify at-risk patients with NAFLD without recourse to liver biopsy on a routine basis. These modalities and algorithms have improved significantly in their diagnosis and staging of fibrosis and NASH in patients with NAFLD, and will likely impact on the number of patients undergoing liver biopsy. \ud \ud Conclusions: Staging for NAFLD can now be performed by a combination of radiological and laboratory techniques, greatly reducing the requirement for invasive liver biopsy

Hepatic artery thrombosis after liver transplantation: Radiologic evaluation

Hepatic artery thrombosis after liver transplantation is a devastating event requiring emergency retransplantation in most patients. Early clinical signs are often nonspecific. Before duplex sonography (combined real-time and pulsed Doppler) capability was acquired in October 1984, 76% of all transplants in this institution referred for angiography with a clinical suspicion of hepatic artery thrombosis had patent arteries. In an effort to reduce the number of negative angiograms, CT, real-time sonography, and pulsed Doppler have been evaluated as screening examinations to determine which patients need angiography. Of 14 patients with focal inhomogeneity of the liver architecture detected by CT and/or real-time sonography, 12 (86%) had hepatic artery thrombosis, one had slow arterial flow with hepatic necrosis, and one had a biloma with a patent hepatic artery. In 29 patients undergoing duplex sonography of the hepatic artery, six (21%) had absence of a Doppler arterial pulse. All six had abnormal angiograms: Four had thrombosis, one had a significant stenosis, and one had slow flow with biopsy-proven ischemia. Of 23 patients with a Doppler pulse, two had hepatic artery thrombosis at surgery. However, real-time sonography demonstrated focal inhomogeneity in the liver in both cases. Our data demonstrate that pulsed Doppler of the hepatic artery combined with real-time sonography of the liver parenchyma currently is the optimal screening test for selecting patients who require hepatic angiography after liver transplantation. A diagnostic algorithm is provided

Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives

Assessing Non-Invasive Liver Function in Patients With Intestinal Failure Receiving Total Parenteral Nutrition-Results From the Prospective PNLiver Trial

Liver abnormalities in intestinal failure (IF) patients receiving parenteral nutrition (PN) can progress undetected by standard laboratory tests to intestinal failure associated liver disease (IFALD). The aim of this longitudinal study is to evaluate the ability of non-invasive liver function tests to assess liver function following the initiation of PN. Twenty adult patients with IF were prospectively included at PN initiation and received scheduled follow-up assessments after 6, 12, and 24 months between 2014 and 2019. Each visit included liver assessment (LiMAx [Liver Maximum Capacity] test, ICG [indocyanine green] test, FibroScan), laboratory tests (standard laboratory test, NAFLD [non-alcoholic fatty liver disease] score, FIB-4 [fibrosis-4] score), nutritional status (bioelectrical impedance analysis, indirect calorimetry), and quality of life assessment. The patients were categorized post-hoc based on their continuous need for PN into a reduced parenteral nutrition (RPN) group and a stable parenteral nutrition (SPN) group. While the SPN group (n = 9) had significantly shorter small bowel length and poorer nutritional status at baseline compared to the RPN group (n = 11), no difference in liver function was observed between the distinct groups. Over time, liver function determined by LiMAx did continuously decrease from baseline to 24 months in the SPN group but remained stable in the RPN group. This decrease in liver function assessed with LiMAx in the SPN group preceded deterioration of all other investigated liver function tests during the study period. Our results suggest that the liver function over time is primarily determined by the degree of intestinal failure. Furthermore, the LiMAx test appeared more sensitive in detecting early changes in liver function in comparison to other liver function tests

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy

Indocyanine green elimination test in orthotopic liver recipients.

OBJECTIVE: To determine its predictive capability on graft quality and resultant clinical outcome, the indocyanine green (ICG) elimination test was performed by a spectrophotometric method and a noninvasive finger-piece method with 50 orthotopic liver transplantations. BACKGROUND: Early detection of poor-functioning hepatic grafts is one of the most important issues in liver transplantation, but no reliable methods exist. METHODS: The ICG test was performed after 50 orthotopic liver transplantations on postoperative days 1, 3, and 7. Indocyanine green elimination constants (K(ICG)) were measured by both a standard spectrophotometric analysis (K(ICG)-B) and by a finger-piece method (K(ICG)-F). The patients were followed for a minimum of 3 months after transplantation. Results of ICG tests were correlated with various clinical determinations. RESULTS: Twelve of the 50 grafts were lost within three months, of which 7 were related to graft failure. Multivariate analysis using the Cox proportional hazard model revealed that K(ICG) on postoperative day 1 was a better predictor of liver-related graft outcome than any of the conventional liver function tests. Furthermore, K(ICG) values showed significant correlation with the severity of preservation injury, longer intensive care unit (ICU) and hospital stay, prolonged liver dysfunction, and septic complications. Correlation of K(ICG) values by the spectrophotometric method with those by the finger-piece method was highly satisfactory in the grafts that had K(ICG)-B <0.15 min-1 (y = 0.868x -0.011, r = .955). CONCLUSION: The ICG elimination test, conducted spectrophotometrically or optically on the day after liver transplantation, is a reliable indicator of graft quality and subsequent graft outcome early after liver transplantation

Clinical-evolutional particularities of the cryoglobulinemic vasculitis in the case of a patient diagnosed with hepatitis C virus in the predialitic phase

Hepatitis C virus (HCV) represents a fundamental issue for public health, with long term evolution and the gradual appearance of several complications and associated pathologies. One of these pathologies is represented by cryoglobulinemic vasculitis, a disorder characterized by the appearance in the patient’s serum of the cryoglobulins, which typically precipitate at temperatures below normal body temperature (37°C) and dissolve again if the serum is heated. Here, we describe the case of a patient diagnosed with HCV that, during the evolution of the hepatic disease, developed a form of cryoglobulinemic vasculitis. The connection between the vasculitis and the hepatic disorder was revealed following treatment with interferon, with the temporary remission of both pathologies and subsequent relapse at the end of the 12 months of treatment, the patient becoming a non-responder. The particularity of the case is represented by both the severity of the vasculitic disease from its onset and the deterioration of renal function up to the predialitic phase, a situation not typical of the evolution of cryoglobulinemia. Taking into account the hepatic disorder, the inevitable evolution towards cirrhosis, and the risk of developing the hepatocellular carcinoma, close monitoring is necessary

Overexpression of the vitronectin v10 subunit in patients with nonalcoholic steatohepatitis: Implications for noninvasive diagnosis of NASH

Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients. On the basis of the assumption that steatohepatitis leads to the remodelling of the liver extracellular matrix (ECM), NASH-specific fragments were in silico analysed for their involvement in the ECM molecular composition. The 10 kDa C-terminal fragment of the ECM prote in vitro nectin (VTN) was then selected as a promising circulating biomarker in discriminating NASH. The analysis of sera of patients provided these major findings: the circulating VTN fragment (i) is overexpressed in NASH patients and positively correlates with the NASH activity score (NAS); (ii) originates from the disulfide bond reduction between the V10 and the V65 subunits. In conclusion, V10 determination in the serum could represent a reliable tool for the noninvasive discrimination of NASH from simple steatosi

Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. NAFLD covers a spectrum that ranges from simple steatosis, nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, to cirrhosis, which is a major risk factor for hepatocellular carcinoma. Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity, type 2 diabetes mellitus and dyslipidemia, with a global prevalence of 25%. NAFLD arises when the uptake of fatty acids (FA) and triglycerides (TG) from circulation and de novo lipogenesis saturate the rate of FA β-oxidation and very-low density lipoprotein (VLDL)-TG export. Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH, and therefore, alterations in liver and serum lipidomic signatures are good indicators of the disease's development and progression. This review focuses on the importance of the classification of NAFLD patients into different subtypes, corresponding to the main alteration(s) in the major pathways that regulate FA homeostasis leading, in each case, to the initiation and progression of NASH. This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments

Intrarenal Resistance Index as a Prognostic Parameter in Patients with Liver Cirrhosis Compared with Other Hepatic Scoring Systems

Background and Aims: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. Methods: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. Results: In 28 patients, a follow-up visit was performed after 22 8 months (group 1). Sixteen patients died during follow-up after 12 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 +/- 0.05) than group 1 patients (RI = 0.72 +/- 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity {[}area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% Cl: 0.518-0.837). Conclusion: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care. Copyright (C) 2012 S. Karger AG, Base