Early Stage Of Liver Cirrhosis Research Articles

Lymphedema in a patient with decompensated cirrhosis

The lymphatic system is critical in body fluid homeostasis. Although lymphatic vascular expansion prevents the development of ascites and oedema in the early stages of liver cirrhosis, compensatory mechanisms cannot achieve this in the advanced stages due to lymphatic dysfunction. A 36-year-old male patient, who had been followed up for cryptogenic cirrhosis for 15 years, had been complaining of excessive swelling in his legs for the last 4 years. Excessive swelling in the legs was accompanied by skin rashes and ulcers, and the leg skin had an orange peel appearance characteristic of lymphedema. Bilateral lower extremity artery and venous system colour Doppler ultrasonography showed that the vascular structures of the right lower extremity arterial and venous system were open, and the flow rate, direction and spectrum were normal. The patient, who could not undergo liver transplantation due to organ limitations, died due to sepsis following lymphedema-induced wound infection. In conclusion, this case suggests that lymphedema should be considered in the presence of oedema in cases of decompensated cirrhosis, and the necessary conservative treatments should be applied.

Segmental analysis of liver cirrhosis with different etiologies: a study based on iodine mixed imaging in port-venous phase.

Computed tomography (CT) in port-venous phase can display the intra-hepatic vessels, and may provide the possibility for segment function evaluation for cirrhosis. To assess the value of iodine mixed imaging of dual-source dual-energy CT in port-venous phase in segmental evaluation of liver cirrhosis with different etiologies. Patients diagnosed with liver cirrhosis were enrolled. Patients without cirrhosis were included as a control group. Each patient underwent iodine-contrast enhanced multi-phase dual-energy CT scanning. Parameters were analyzed by SPSS, version 22.0, and Medcalc. In total, 256 patients were investigated, including 114 Child-Pugh A, 51 Child-Pugh B, 41 Child-Pugh C and 50 control patients. Total iodine content (ICt)/body surface area (BSA) in the cirrhosis group was significantly lower than the control group (P < 0.05) and the standardized-iodine parameter (SI) of each segment decreased with cirrhosis progression. In Child-Pugh A and B, SI increased more significantly in the caudal and lateral segment in A (alcholism) than in the V (virus-related) and N (non-alcoholic steatohepatitis) groups (P < 0.001). ICt/BSA showed the best diagnosis power of cirrhosis with an area under the curve of 0.765, sensitivity of 76.0% and specificity of 71.8%. Blood flow compensated in the left lateral and caudal lobe in the early stage of liver cirrhosis. The compensation in alcoholism in the middle and early stages is significantly higher than that of V and N cirrhosis. Iodine mixed imaging in portal phase may provide the possibility of an incremental value in segmented blood flow perfusion and functional evaluation of liver cirrhosis on a morphological basis.

A Three-Dimensional Digital Model for Early Diagnosis of Hepatic Fibrosis Based on Magnetic Resonance Elastography.

Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the disease. Despite the good progress made with the liver stiffness map (LSM) based on magnetic resonance elastography (MRE), there are still some limitations that need to be overcome, including manual focus determination, manual selection of regions of interest (ROIs), and discontinuous LSM data without structural information, which makes it impossible to evaluate the liver as a whole. In this study, we propose a novel three-dimensional (3D) digital model for the early diagnosis of hepatic fibrosis based on MRE. MRE is a non-invasive imaging technique that employs magnetic resonance imaging (MRI) to measure the liver stiffness at the scanning site through human-computer interaction. Studies have indicated a significant positive correlation between the LSM obtained through MRE and the degree of hepatic fibrosis. However, for clinical purposes, a comprehensive and precise quantification of the degree of hepatic fibrosis is necessary. To address this, the concept of Liver Stiffness Distribution (LSD) was proposed in this study, which refers to the 3D stiffness volume of each liver voxel obtained by the alignment of 3D liver tissue images and MRE indicators. This provides a more effective clinical tool for the diagnosis and treatment of hepatic fibrosis.

Segmentation algorithm can be used for detecting hepatic fibrosis in SD rat

BackgroundLiver fibrosis is an early stage of liver cirrhosis. As a reversible lesion before cirrhosis, liver failure, and liver cancer, it has been a target for drug discovery. Many antifibrotic candidates have shown promising results in experimental animal models; however, due to adverse clinical reactions, most antifibrotic agents are still preclinical. Therefore, rodent models have been used to examine the histopathological differences between the control and treatment groups to evaluate the efficacy of anti-fibrotic agents in non-clinical research. In addition, with improvements in digital image analysis incorporating artificial intelligence (AI), a few researchers have developed an automated quantification of fibrosis. However, the performance of multiple deep learning algorithms for the optimal quantification of hepatic fibrosis has not been evaluated. Here, we investigated three different localization algorithms, mask R-CNN, DeepLabV3+, and SSD, to detect hepatic fibrosis.Results5750 images with 7503 annotations were trained using the three algorithms, and the model performance was evaluated in large-scale images and compared to the training images. The results showed that the precision values were comparable among the algorithms. However, there was a gap in the recall, leading to a difference in model accuracy. The mask R-CNN outperformed the recall value (0.93) and showed the closest prediction results to the annotation for detecting hepatic fibrosis among the algorithms. DeepLabV3+ also showed good performance; however, it had limitations in the misprediction of hepatic fibrosis as inflammatory cells and connective tissue. The trained SSD showed the lowest performance and was limited in predicting hepatic fibrosis compared to the other algorithms because of its low recall value (0.75).ConclusionsWe suggest it would be a more useful tool to apply segmentation algorithms in implementing AI algorithms to predict hepatic fibrosis in non-clinical studies.

Evidence of Ventricular Arrhythmogenicity and Cardiac Sympathetic Hyperinnervation in Early Cirrhotic Cardiomyopathy

Cirrhotic cardiomyopathy (CMP) is associated with altered cardiac electrophysiological (EP) properties, which leads to the risk of ventricular arrhythmias (VAs). We aimed to evaluate the EP properties, autonomic, and structural remodeling in a rabbit model with early liver cirrhosis (LC). Twelve rabbits were assigned to the sham and LC groups. The early-stage LC was induced by the ligation of the common bile duct. All rabbits received an EP study, VA inducibility test, myocardial, and liver histology staining. Western blot analyses of protein expression and tyrosine hydroxylase stain for sympathetic nerves were performed. The effective refractory period the LC group was significantly longer than the sham group [i.e., left ventricle (LV) 205.56 ± 40.30 vs. 131.36 ± 7.94 ms; right ventricle (RV) 206.78 ± 33.07 vs. 136.79 ± 15.15 ms; left atrium (LA) 140.56 ± 28.75 vs. 67.71 ± 14.29 ms; and right atrium (RA) 133.78 ± 40.58 vs. 65.43 ± 19.49 ms, all p < 0.01], respectively. The VA inducibility was elevated in the LC group when compared with the sham group (i.e., 21.53 ± 7.71 vs. 7.76 ± 2.44%, p = 0.013). Sympathetic innervation (102/μm2/mm2) was increased in all cardiac chambers of the LC group compared with the sham group (i.e., LV 9.11 ± 4.86 vs. 0.17 ± 0.15, p < 0.01; RV 4.36 ± 4.95 vs. 0.18 ± 0.12, p = 0.026; LA 6.79 ± 1.02 vs. 0.44 ± 0.20, p = 0.018; and RA 15.18 ± 5.12 vs. 0.10 ± 0.07, p = 0.014), respectively. Early LC is presented with an increased ventricular vulnerability, structural heterogeneity, and sympathetic innervation. Close monitoring for fatal arrhythmias is warranted in patients with early stages of LC.

Clinical significance of the latency period of abnormal ammonia metabolism in chronic liver disease: Proposal of a new concept.

The liver is a key organ in regulating metabolism, and chronic liver disease is associated with several metabolic disorders. In the later stages of liver cirrhosis, the urea cycle is impaired, which disrupts of ammonia detoxification and eventually causes hyperammonemia and hepatic encephalopathy. Although hyperammonemia is not detected during the period between the late stage of chronic hepatitis and the early stage of liver cirrhosis, hepatic albumin synthesis capacity decreases as the fibrosis progresses. Increased ammonia levels are associated with a decreased capacity of the liver to synthesize albumin as well as activation of hepatic stellate cells, which promote fibrosis. Herein, we discuss the possibility that abnormal ammonia metabolism might play an important role in the pathogenesis of liver diseases even without hyperammonemia. We consider the disease period without hyperammonemia as the latency period of abnormal ammonia metabolism and discuss its clinical significance.

Worse Outcomes Associated With Liver Transplants: An Increasing Trend.

Background and aimSince individuals in the early stages of liver cirrhosis are typically asymptomatic, the prevalence of liver cirrhosis may be underestimated. Liver cirrhosis has a significant morbidity and mortality rate, with 1.03 million deaths worldwide each year. For end-stage liver disease, liver transplantation is a potential therapeutic option. The goal of our research was to examine the current trend in liver transplants using data from a national database.MethodsUsing the International Classification of Diseases (ICD)-9 codes, we identified individuals who had a liver transplant during the index hospital admission in the Nationwide Inpatient Sample from 2007 to 2011. This national sample of patients is from the United States. We looked at the yearly trend in liver transplants and related outcomes, such as duration of hospitalization (DOH), hospital expenses, and mortality in the hospital. In order to find determinants of mortality, we used a multivariate analysis.ResultsThere were 25,331 patients hospitalized (weighted for national estimate). Between 2007 and 2011, the number of transplants grew by 1.2%. The majority of transplant recipients were Caucasian (57%), with an average age of 54 years, had a private healthcare plan (53%), and had average earnings in the upper quartile by zip code (26%). Patients with a higher Charlson Comorbidity Index (79% had a score of four) were more likely to be admitted to a southern hospital (33%), an academic hospital (>99%), and a large capacity hospital (90%). Seventy percent of liver transplant recipients received cadaver donors. Hepatitis C was the most prevalent reason for transplant (30%), followed by hepatocellular carcinoma (HCC) (29%) and alcoholic liver disease (25%). In 2011, compared to 2007, there was an upward rise in fatality (from 3.8% to 5.1%), average hospital expenditures (from $335,504 to $498,369), and DOH (from 17.4 to 22.7 days). The cost of hospitalization was two billion dollars per year. The independent variables related to an increased mortality on multivariate analysis were African American race (OR: 2.0, 95%, CI: 1.2-3.2; p=0.005) and large capacity hospitals (OR: 2.5, 95% CI: 1.6-4.1; p=0.0002). Predictors linked to lower mortality included private healthcare coverage (vs. Medicare: OR: 0.7, 95%, CI: 0.51-0.97; p=0.03), academic hospital (OR: 0.6, 95% CI: 0.4-0.8; p=0.005), cadaver donor (OR: 0.6, 95% CI: 0.5-0.8; p=0.002), HCC (OR: 0.6, 95% CI: 0.4-0.9; p=0.01), and non-alcoholic steatohepatitis (NASH) cirrhosis (OR: 0.4, 95% CI: 0.2-0.9; p=0.02).ConclusionOur study found an increasing trend in worse outcomes (increased mortality, average hospital costs, and average DOH) after a liver transplant. Patients of the African American race and large capacity hospitals were associated with a higher risk of death, whereas private healthcare plans, academic hospitals, cadaver donors, HCC, and NASH cirrhosis were associated with a lower risk.

Controversies in anticoagulation therapy in patients with cirrhosis.

This article aims to review the latest literature on prophylactic and therapeutic anticoagulation and the safety profile of anticoagulants in patients with cirrhosis. The understanding of hematological hemostasis is cirrhotic patients has changed drastically in recent years. Although in the past, cirrhotic patients were often considered to be 'auto-anticoagulated' and at higher risk of bleeding, recent studies have demonstrated that there may be a rebalance in procoagulation and anticoagulation factors in patients with cirrhosis. This, and clinical experience, suggest that cirrhotic patients are at risk of development of venous thrombosis, pulmonary embolism and ischemic strokes and as such, the best management approaches in these patients remains controversial. The bulk of the data suggest that patients with cirrhosis who are at risk for thrombotic or embolic complications should be anticoagulated. However, it is imperative that they be closely monitored. The medical literature on anticoagulation in patients with liver cirrhosis is conflicting and limited to small sample observational studies. However, most studies suggest that in patients with early stages of liver cirrhosis and no history of varices, anticoagulation appears to be well tolerated.

Preoperative evaluation of the degree of liver fibrosis based on matter-element analysis using serological indicators in patients with hepatocellular carcinoma.

Evaluation of the degree of liver fibrosis is an important basis for the clinical diagnosis and treatment of patients with hepatocellular carcinoma (HCC). It is meaningful to make a preoperative evaluation with non-invasive methods. In the current study, 12 commonly used preoperative serological indicators from 161 HCC patients with different degree of liver fibrosis were collected retrospectively, and 8 of the indicators (ALB, PA, TBil, INR, AST, GGT, ALP, and PT) were ultimately used in matter-element analysis to create a formula. The relationship between those results and the histological sub-classification of the Laennec liver fibrosis scoring system was analyzed. The calculated value of R from this formula will indicate the differing degree of liver fibrosis in a patient: i) the value of 0.802 ≤ R < 1 indicates the early stage of liver cirrhosis, which corresponds to Laennec stages 0-3; ii) the value of 0.752 ≤ R < 0.802 indicates the mild stage of liver cirrhosis, which corresponds to Laennec stage 4A; iii) the value of 0.698 ≤ R < 0.752 indicates the moderate stage of liver cirrhosis, which corresponds to Laennec stage 4B; and iv) the value of 0.444 ≤ R < 0.698 indicates the severe stage of liver cirrhosis, which corresponds to Laennec stage 4C. The hope is that this formula for preoperative evaluation of the degree of liver fibrosis using non-invasive methods would be useful in the clinical diagnosis and treatment of patients with HCC in the future.

Classification of mice hepatic granuloma microscopic images based on a deep convolutional neural network

Hepatic granuloma develops in the early stage of liver cirrhosis which can seriously injury liver health. At present, the assessment of medical microscopic images is necessary for various diseases and the exploiting of artificial intelligence technology to assist pathology doctors in pre-diagnosis is the trend of future medical development. In this article, we try to classify mice liver microscopic images of normal, granuloma-fibrosis1 and granuloma-fibrosis2, using convolutional neural networks (CNNs) and two conventional machine learning methods: support vector machine (SVM) and random forest (RF). On account of the included small dataset of 30 mice liver microscopic images, the proposed work included a preprocessing stage to deal with the problem of insufficient image number, which included the cropping of the original microscopic images to small patches, and the disorderly recombination after cropping and labeling the cropped patches In addition, recognizable texture features are extracted and selected using gray the level co-occurrence matrix (GLCM), local binary pattern (LBP) and Pearson correlation coefficient (PCC), respectively. The results established a classification accuracy of 82.78% of the proposed CNN based classifiers to classify 3 types of images. In addition, the confusion matrix figures out that the accuracy of the classification results using the proposed CNNs based classifiers for the normal class, granuloma-fibrosis1, and granuloma-fibrosis2 were 92.5%, 76.67%, and 79.17%, respectively. The comparative study of the proposed CNN based classifier and the SVM and RF proved the superiority of the CNNs showing its promising performance for clinical cases.

Study of trace elements in liver cirrhosis patients and their role in prognosis of disease.

The objectives of this study are to evaluate trace elements in patients with liver cirrhosis and to assess their association with severity of the disease. One hundred fifty cirrhotic subjects of either sex ranging in age from 20-70 years were included in the study, and the results were compared with 50 age- and sex-matched healthy control subjects. All cirrhotic subjects were assessed for severity of disease as mild (Child A), moderate (Child B), and severe (Child C) as per Child-Pugh classification. Routine investigations were done and trace elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption spectrophotometer. Serum level of copper was found significantly increased in patients with liver cirrhosis as compared to control group. Whereas serum zinc, selenium, and magnesium levels were significantly decreased in cirrhotic subjects as compared to controls. Trace elements were compared with severity of liver cirrhosis. Serum copper concentration was slightly increased in patients with more severe clinical state of liver cirrhosis; however, mean level difference of copper among the Child-Pugh groups were statistically not significant. Moreover, there was no significant correlation between copper and Child-Pugh Score. However, copper showed a significant negative correlation with zinc. Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score. Trace element abnormalities may reflect the condition of liver dysfunction. These results suggest that liver dysfunction may alter the metabolism of trace elements. Our study shows that micronutrients status in liver cirrhosis correlates well with severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic patients may prevent progression of disease and development of complications; however, further research needs to be done.

Insulin resistance as early sign of hepatic dysfunction in liver cirrhosis

Glucose intolerance characterized by postprandial hyperglycemia and hyperinsulinemia is commonly seen in patients with liver cirrhosis (LC). The aim of this study is to clarify the relation between glucose intolerance and disorder of liver function in patients with LC. The 75 g oral glucose tolerance test (75 g OGTT) and the hyperinsulinemic euglycemic clamp combined with 0.2 g/kg oral glucose load (HECGL) were conducted in 61 patients with LC. Based on the results of 75 g OGTT, the 61 patients with LC were divided into groups, 21 (34.4%) patients with normal glucose tolerance (LC-NGT), 12 (19.7%) patients with impaired glucose tolerance (LC-IGT) and 28 (45.9%) patients with diabetes mellitus (LC-DM). Fasting plasma glucose (FPG) level was normal in 50 (82.0%) patients with LC. All patients with LC showed insulin resistance in both peripheral (skeletal and adipose) and hepatic tissues evaluated by HECGL, although significant correlation between the degree of glucose intolerance and the severity of hepatic dysfunction was not observed. Insulin resistance in both liver and peripheral tissues is the early sign in the patients with LC. This fact indicates that nutritional care from early stages of LC would be necessary in the patients.

Effects of late evening snack including branched‐chain amino acid on the function of hepatic parenchymal cells in patients with liver cirrhosis

A late evening snack (LES) improves protein-energy malnutrition due to overnight starvation and the catabolic state in patients with liver cirrhosis. Our aim was to examine whether LES including a branched-chain amino acid (BCAA) could maintain hepatic reserve and the function of hepatic parenchymal cells in patients with liver cirrhosis, including those in the early stage of disease. Seventeen patients with liver cirrhosis received LES with a BCAA-enriched nutrient mixture. During the study period, each patient was instructed on energy and protein intake. Indicators of liver function measured at 6 months included maximum asialoscintigraphic removal (Rmax: indicator of total liver receptors), asialoscintigraphic imaging grade, serum albumin, ammonia, tyrosine and BTR (molar ratio of branched-chain amino acids to tyrosine). Serum albumin levels, BTR and tyrosine levels of the 17 patients were significantly improved after nutrient treatment. In patients with Rmax of 0.2 or higher, serum albumin level and tyrosine level were significantly improved. LES with BCAA-enriched nutrient therapy can improve protein malnutrition in patients with liver cirrhosis, and is more useful in the early stages of liver cirrhosis in improving hepatic parenchymal cell mass.

Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized readiness potential (LRP) measurement elicited by a visuospatial compatibility task (Simon task). Stimulus-triggered LRPonset reflects the time in which response is selected, while response-triggered LRP onset reflects motor execution. Cirrhotic patients showed delayed reaction times (RTs) compared to controls, particularly those with trial-making test A (TMT-A) or electroencephalogram (EEG) alterations. Stimulus-triggered LRP onset was found to be delayed in cirrhotic patients compared to controls, with a significant Group-versus-Condition interaction, showing a reduced cognitive ability to cope with interfering codes, even in patients without minimal HE (MHE). Response-triggered LRP was found to be delayed only in the patients with TMT-A or EEG alterations. In conclusion, cirrhotic patients without overt HE display a psychomotor slowing, depending first lyon response inhibition and only later accompanied by impaired motor execution.

High relative fat-free mass is important for maintaining serum albumin levels in patients with compensated liver cirrhosis

In patients with liver cirrhosis, hypoalbuminemia causes edema and ascites, and a reduction in the quality of life. Since musculature is catabolized to supply amino acids for albumin synthesis in malnutritional cirrhotic patients, muscular volume is hypothesized to play an important role in albumin production. Therefore, we investigated the correlation between serum albumin levels and the fat-free mass (FFM) in cirrhotic patients. Fifty-seven patients (26 males and 31 females) with compensated liver cirrhosis were evaluated. Patients with edema or ascites were excluded from the study. Healthy volunteers (n = 104; 48 males and 56 females) were also evaluated as controls. FFM was measured using 5-500 kHz multifrequency bioelectric impedance analysis. To minimize the difference in FFM distribution between males and females, we introduced a new marker, relative FFM (rFFM), which represents the ratio of FFM in a patient relative to that in a volunteer of the same height. Following FFM measurement, the serum albumin levels of patients were assayed monthly. In patients with active cirrhosis (alanine aminotransaminase (ALT) > 50 U/L), both albumin (the difference between maximum and minimum levels) and the standard deviation of albumin levels (SD-albumin) during the observation period showed a significant correlation with rFFM. Multiple linear regression analysis using variables such as rFFM, platelet number, and serum cholesterol levels, choline esterase, albumin, bilirubin, and ALT revealed that rFFM and ALT were significant and independent factors that influenced albumin or SD-albumin in cirrhotic patients. Our results indicate that cirrhotic patients with high rFFM showed less of a decrease in albumin levels, and that the muscle volume is one of the most important factors for maintaining serum albumins level in active cirrhosis. Exercise and protein-rich nutrition at the early stage of liver cirrhosis may be advisable for maintaining or increasing muscular volume.

Hematotesticular barrier is altered from early stages of liver cirrhosis: effect of insulin-like growth factor 1.

The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophyso-gonadal axis in rats with no ascitic cirrhosis. Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk, were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 microg/100 g.d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12). Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<0.01 vs untreated cirrhotic group). The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

Beneficial effects of branched-chain amino acids on altered protein and amino acid metabolism in liver cirrhosis: evaluation in a model of liver cirrhosis induced in rats with carbon tetrachloride

The effect of branched-chain amino acids (BCAA) on the metabolism of protein, amino acids and ammonia was examined in rats with cirrhosis, with a special emphasis on the efficacy of early administration of BCAA. Liver cirrhosis was induced in rats by intraperitoneal injections of carbon tetrachloride (CCl 4). The rats were divided into three groups: early-, late- and untreated. The early- and late-treated groups were given BCAA rich food from the early and late stage of liver cirrhosis, while the untreated group was given standard food throughout. Concentrations of amino acids and ammonia in the plasma and the ornithine carbamyl transferase (OCT) activity in the liver were evaluated, and compared with control group after 15 weeks maintenance. Ammonia was significantly higher in the late- and untreated groups, but not in the early-treated group. BCAA, tyrosine, and methionine were significantly lower in the untreated and late-treated groups. Glutamine increased significantly in the un-, late- and early-treated groups. However, no significant differences were found among three groups. A significant difference was found in 3-methyl histidine (3-MH) between the early- and late-treated groups. This study suggests that the administration of BCAA from early stage of liver cirrhosis inhibits breakdown of protein and improves metabolism of protein, amino acids and ammonia.

18 OC 13C-aminopyrine breath test discriminates the early stage of liver cirrhosis

18 OC 13C-aminopyrine breath test discriminates the early stage of liver cirrhosis

Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis

Background/Aims: In order to ascertain whether malnutrition is an early-onset feature of liver cirrhosis and whether the anabolic hormone insulin-like growth factor I (IGF-I) could be useful in the treatment of this complication, we analyzed the nutritional alterations present in rats with early-stage liver cirrhosis and the effects of IGF-I on nutritional parameters in these animals. Methods: After a 24 h fast, a 15N-enriched diet was administered for 5 days to normal control rats and to cirrhotic rats receiving subcutaneous injections of vehicle (Group 1) or IGF-I, 2 μg·100 g bw −1·day −1, (Group 2) during the 5 experimental days. 15N, a stable N isotope, was measured in biological samples by mass spectrometry. Results: Compared with control rats, Group 1 animals showed significant reductions in N intake and food efficiency ( p<0.05, both). In addition, the weight of the gastrocnemius muscle, its total N content and the dietary N content of this muscle were significantly lower in Group 1 than in control animals ( p<0.05, all). In rats from Group 2, mean values of N intake, food efficiency, gastrocnemius N content and the amount of dietary N incorporated into this muscle were similar to those in control rats, and (with the exception of gastrocnemius N total content) significantly higher than those in non-treated cirrhotic rats ( p<0.05, all). Conclusions:A variety of nutritional disturbances were detected in rats from the early stages of liver cirrhosis. Low doses of IGF-I were found to reverse most of these changes. These results stimulate further studies to determine whether IGF-I might be useful in the correction of the malnutrition present in patients with liver cirrhosis.

慢性肝疾患の経過過程にみられる多様性肝細胞群に関する検討

Heterogeneous groups of hepatocytes with different staining characteristics to eosin are found in patients with various chronic liver diseases. These staining characteristics seem to have some relationship to the progression of chronic liver diseases. To examine this relationship, biopsy specimen from 184 liver disease cases, were examined by routine methods, histochemical methods for enzyme quantitaion. RNA staining and immunohistochemical, identification of albumin. The results were as follows.1) Eosin-intense hepatocytes occupying part of the liver lobule or forming a whole nodule had a high incidence of binucleated cells; normal or elevated levels of glucose 6-phosphatase, succinate dehydrogenase and glutamic-oxaloacetic transaminase; increased nucleolar and cytoplasmic RNA; many albumin containing hepatocytes; and normal glucose 6-phosphate dehydrogenase activity. These eosin-intense hepatocytes seemed to be normal except for the intense staining of eosin and these hepatocytes were probably at the stage of regeneration. Pale hepatocytes with a weak affinity for eosin showed reduced function and to be dedifferentiated. Nodules containing these plale hepatocytes were more expansive.2) Hepatocytes with different staining characteristics for eosin were found only in patients with chronic hepatitis with sublobular necrosis and liver cirrhosis. The eosin stained group was most frequently observed in the early stage of liver cirrhosis and disappered at late stages. Eosin staining was weak in hepatocytes with progressively increased, well developed cirrhosis with expansive regenerating nodules.3) Correlations were present in a large number of cases between the size of the hepatic necrosis and the incidence of eosin-intense hepatocytes. This relationship was most prominent at the stage of resorbtion after hepatic necrosis.4) In at least some specimens, eosin-intense hepatocytes were found around the portal vein. An adequate blood supply may thus be important factor for eosin intense staining.