Fluorescence spectroscopy to diagnose hepatic steatosis in a rat model of fatty liver

Steatosis is diagnosed on the basis of the macroscopic aspect of the liver evaluated by the surgeon at the time of organ extraction or by means of a frozen biopsy. In the present study, the applicability of laser-induced fluorescence (LIF) spectroscopy was investigated as a method for the diagnosis of different degrees of steatosis experimentally induced in rats. Rats received a high-lipid diet for different periods of time. The animals were divided into groups according to the degree of induced steatosis diagnosis by histology. The concentration of fat in the liver was correlated with LIF by means of the steatosis fluorescence factor (SFF). The histology classification, according to liver fat concentration was, Severe Steatosis, Moderate Steatosis, Mild Steatosis and Control (no liver steatosis). Fluorescence intensity could be directly correlated with fat content. It was possible to estimate an average of fluorescence intensity variable by means of different confidence intervals (P=95%) for each steatosis group. SFF was significantly higher in the Severe Steatosis group (P < 0.001) compared with the Moderate Steatosis, Mild Steatosis and Control groups. The various degrees of steatosis could be directly correlated with SFF. LIF spectroscopy proved to be a method capable of identifying the degree of hepatic steatosis in this animal model, and has the potential of clinical application for non-invasive evaluation of the degree of steatosis.

Meningeal tumor: A rare extrahepatic association in patients with polycystic liver disease enrolled for liver transplantation

In the present study, we described a rare association of polycystic liver disease (PCLD) with intracranial meningiomas in patients included on a liver transplant list, focusing on the diagnosis, treatment and possible association with any genetic alterations. Two female patients, aged 39 and 49 years were included on a liver transplant list due to extensive PCLD, with symptoms related to an abdominal compartmental syndrome. Screening for extrahepatic manifestation revealed a right frontal meningioma in the first patient, and a parietal posterior calcified meningioma in the second patient, measuring 1 and 7x3x2 cm in diameter, respectively. Following tumor removal, the histological pattern was compatible with fibrous and transitional meningioma, respectively. Cytogenetic studies conducted following surgery did not reveal any changes in metaphase chromosomes. The postoperative follow-up for the two patients was uneventful, without complications, with the patients remaining on a liver transplant waiting list. We conclude that screening for extrahepatic manifestations of PCLD is mandatory, as certain lesions require treatment prior to liver transplantation. The lack of a genetic or familial association between these two cases show they are likely to have occurred by chance, rather than representing a previously unrecognized association between polycystic liver disease and cranial meningioma.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Evaluation of nutritional indicators and body composition in patients with advanced liver disease enrolled for liver transplantation

PURPOSE: Malnutrition is prevalent in patients with advanced liver disease (LD) related to multifactorial causes. Fluid retention can underestimate the nutritional status based on anthropometric measures. We evaluated nutritional indicators and body composition (BC) in patients with liver cirrhosis and correlated them with LD severity. METHODS: Forty three patients with LD enrolled for liver transplantation were evaluated by Anthropometric measures, subjective evaluation (Global Assessment of Nutritional Status - SGA) and biochemical indicators. Single-frequency electrical bioimpedance (SFE-BIA) was used to evaluate body composition (BC). It measured resistance (R), reactance (Xc) and the phase angle (PA). LD severity was estimated by Child-Pugh and Meld criteria (Model for End-Stage Liver Disease). RESULTS: Child-Pugh index between patients was 7.11±1.70 and Meld was 12.23±4.22. Arm Circumference, Arm Muscle Circumference and Arm Muscle Area, SGA, hemoglobin, hematocrit and albumin showed better correlation with disease severity. Xc and PA showed correlation both with Meld and Child-Pugh score when BC were evaluated. PA was depleted in 55.8% of the patients. CONCLUSIONS: Diagnosis of malnutrition varied according to the method. Global assessment of nutritional status showed better correlation with disease severity than with objective methods. Single-frequency electrical bioimpedance for body composition analysis in cirrhotic patients must be cautiously used; however, primary vectors seems to be valid and promising in clinical practice.

Ultrasound analysis of a canine patient with renal disease and chronic liver disease undergoing treatment with intravenous stem cells

With the improvement in quality of life of animals, it is increasingly frequent clinical care of elderly patients, which present renal disorders, including chronic renal failure. Recent studies report the use of stem cells to treat renal failure, which would improve the levels of urea and creatinine, and in renal ultrasound evaluation. With the present work, the idea is to report a case of ultrasonographic evaluation in a patient with chronic renal failure, liver disease and splenic nodule, which underwent stem cell therapy, where there was an improvement in the sonographic evaluation of part of the liver.

Assessment of health-related quality of life and related factors in patients with chronic liver disease

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

Diagnostic performance and accuracy of 3-D spoiled gradient-dual-echo MRI with water- and fat-signal separation in liver-fat quantification: comparison to liver biopsy

To prospectively evaluate a 3-dimensional spoiled gradient-dual-echo (3D SPGR-DE) magnetic resonance imaging (MRI) sequence for the qualitative and quantitative analysis of liver fat content (LFC) in patients with the suspicion of fatty liver disease using histopathology as the standard of reference.

Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis

To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).

Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse

Alcohol-induced liver disease (ALD) is a leading cause of nonaccident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively nonspecific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study, the metabolic changes associated with ALD were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-beta-d-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of a metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model.

UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model

Since the development and prognosis of alcohol-induced liver disease (ALD) vary significantly with genetic background, identification of a genetic background-independent noninvasive ALD biomarker would significantly improve screening and diagnosis. This study explored the effect of genetic background on the ALD-associated urinary metabolome using the Ppara-null mouse model on two different backgrounds, C57BL/6 (B6) and 129/SvJ (129S), along with their wild-type counterparts. Reversed-phase gradient UPLC-ESI-QTOF-MS analysis revealed that urinary excretion of a number of metabolites, such as ethylsulfate, 4-hydroxyphenylacetic acid, 4-hydroxyphenylacetic acid sulfate, adipic acid, pimelic acid, xanthurenic acid, and taurine, were background-dependent. Elevation of ethyl-β-d-glucuronide and N-acetylglycine was found to be a common signature of the metabolomic response to alcohol exposure in wild-type as well as in Ppara-null mice of both strains. However, increased excretion of indole-3-lactic acid and phenyllactic acid was found to be a conserved feature exclusively associated with the alcohol-treated Ppara-null mouse on both backgrounds that develop liver pathologies similar to the early stages of human ALD. These markers reflected the biochemical events associated with early stages of ALD pathogenesis. The results suggest that indole-3-lactic acid and phenyllactic acid are potential candidates for conserved and pathology-specific high-throughput noninvasive biomarkers for early stages of ALD.