Fatty Liver Changes Research Articles

Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption

Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dilation, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-?B protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-?B signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.

NON-ALCOHOLIC FATTY LIVER DISEASE IN THE CONTEXT OF ALTERED GUT MICROBIOTA

The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota. Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed. Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.

Clinical Utility of Change in Nonalcoholic Fatty Liver Disease Activity Score and Change in Fibrosis in NAFLD

The Nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) has been applied as a method for evaluating treatment response, and a ≥2-point improvement in NAS has been commonly used as an accepted end point in phase 2b clinical trials in nonalcoholic steatohepatitis.1,2 Although liver fibrosis is the strongest histologic predictor of liver-related outcome and all-cause mortality in NAFLD,3,4 the association between change in NAS and change in fibrosis stage has not been fully verified. Therefore, we aimed to examine the association between change in NAS and change in fibrosis stage in well-characterized patients with NAFLD who had a paired liver biopsy assessment.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer. This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group. Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients. Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.

Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study

BackgroundNonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels.MethodsWe designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models.ResultsThe change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group.ConclusionsThe incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.

SUN-912 The Rare Men of Mississippi Complications in the Diagnosis of Multiple Endocrine Neoplasia Type 1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder associated with tumors of the parathyroid glands, pituitary gland, and gastroenteropancreatic cells caused by mutations of the MEN1 tumor-suppressor gene. Thescarcity with which this syndrome is encountered makes diagnosis challenging in rural settings. Clinical Case: A 34-year-old male presented to the Emergency Department complaining ofintermittent abdominal pain for the past year, that was associated with nausea, vomiting, and diarrhea. Past medical history was significant for hyperparathyroidism treated with parathyroidectomy, nephrolithiasis, and alcohol-induced chronic pancreatitis. Initial laboratory studies revealed elevated corrected calcium (11.5 mg/dL, n:7.6-10.6 mg/dL) with a subsequent elevated parathyroid hormone level (105, n:14-72 pg/mL). CT scan of the abdomen and pelvis revealed fatty liver changes, nonobstructive nephrolithiasis and pancreatic calcifications. Due to his recurrent symptoms, gastroenterology was consulted for esophagogastroduodenoscopy that revealed erosive esophagitis with multiple duodenal ulcers. The patient was started on a high dose Proton Pump Inhibitor IV and treated supportively. His symptoms improved within a few days. Additional studies were obtained including a gastrin level and H. pylori antigen testing that required sending out to an outside laboratory for analysis. He was discharged with close outpatient follow up scheduled, but then was readmitted two days later with recurrent symptoms. The patient was again treated with supportive care, and was able to provide additional family history revealing parathyroid and ulcer disease in both his father and paternal grandmother, which triggered suspicion for multiple endocrine neoplasia type 1. His gastrin level returned, and was found to be elevated (489 pg/mL, n < 100) with a negative H. pylori antigen, supporting the diagnosis of MEN1. Further diagnostic testing was performed, revealing an elevated serum chromogranin A level (117 ng/mL, n < 15) and abnormalities on MEN1 genetic testing. An Octreotide scan was then performed, showing a single intense area of uptake near the caudate lobe of liver. At this time, he was transferred to a tertiary medical center for further evaluation and management. Conclusion: This case illustrates the significance of suspicion for multiple endocrine neoplasia and the value of a complete history. Additionally, while a serum chromogranin A level can be nonspecific, it can be obtained in an outpatient setting to help differentiate neuroendocrine pathology from other etiologies. Though the symptoms of MEN1 patients can mimic many other disease processes, recognition of symptoms is critical for medical communities to provide swift treatment.

Effect of Exercise on NAFLD and Its Risk Factors: Comparison of Moderate versus Low Intensity Exercise.

Background and Aims: Lifestyle (exercise and dietary) modification is the mainstay of treatment for non-alcoholic fatty liver disease (NAFLD). However, there is paucity of data on effect of intensity of exercise in management of NAFLD, and we aimed to study the effect of variable intensities of exercise on NAFLD.Methods: The study was performed in the Department of Gastroenterology of the SCB Medical College, Cuttack and the Biju Patnaik State Police Academy, Bhubaneswar. The subjects were police trainees [18 in a moderate intensity exercise group (MIG) and 19 in a low intensity exercise group (LIG)] recruited for a 6-month physical training course (261.8 Kcalorie, 3.6 metabolic equivalent in MIG and 153.6 Kcalorie, 2.1 metabolic equivalent in LIG). NAFLD was diagnosed by ultrasonography, with exclusion of all secondary causes of steatosis. All participants were evaluated by anthropometry (weight, height, body mass index (BMI), waist circumference), assessed for blood pressure and biochemical parameters (blood glucose, liver function test, lipid profile, serum insulin), and subjected to transabdominal ultrasonography before and after 6 months of physical training, and the results were compared.Results: Both the groups had similar BMI, fasting plasma glucose, AST, gamma-glutamyl transpeptidase, insulin, and homeostatic model assessment-insulin resistance (known as HOMA-IR) (p>0.05). However, subjects in the LIG were older and had lower alanine transaminase, higher triglycerides and lower high-density lipoproteins than MIG subjects. There was a significant reduction in BMI (27.0±2.1 to 26.8±2.0; p=0.001), fasting blood glucose (106.7±21.6 to 85.8±19.0; p<0.001), serum triglycerides (167.5±56.7 to 124.6±63.5; p=0.017), total cholesterol (216.8±29.2 to 196.7±26.6; p=0.037), low-density lipoprotein cholesterol (134.6±21.4 to 130.5±21.9; p=0.010), serum aspartate transaminase (39.3±32.2 to 30.9±11.4; p<0.001), serum alanine transaminase (56.6±28.7 to 33.0±11.3; p<0.001) and HOMA-IR (2.63±2.66 to 1.70±2.59; p<0.001) in the MIG. However, changes in these parameters in the LIG were non-significant. Hepatic steatosis regressed in 66.7% of the NAFLD subjects in the MIG but in only 26.3% of the LIG NAFLD subjects (p=0.030).Conclusions: Moderate rather than low intensity physical activity causes significant improvement in BMI, serum triglycerides, cholesterol, serum transaminases and HOMA-IR, and regression of ultrasonographic fatty change in liver among NAFLD subjects.

Discussion on the curative effect and mechanisms of berberine in rats with non-alcoholic fatty liver

Objective: To observe the curative effects of berberine in rats with high-fat diet induced non-alcoholic fatty liver and to further explore its possible mechanism. Methods: Twenty-six Sprague-Dawley rats (120-160 g) were randomly divided into 3 groups: control group (n = 8), model group (n = 10) and treatment group (n = 8). Rats in the control group were fed with regular diet, and the model group and the treatment group were fed a high-fat diet. At the 12th week, two rats in the in the model group were sacrificed to verify whether model was successful established. Subsequently, treatment group rats were given a gavage of berberine at a dose of 150 mg·kg(-1)·d(-1) for 4 weeks, and the control and the model group rats were given the same dose of normal saline. Rats were sacrificed at week 16th. HE staining was used to observe the changes in the intestinal mucosa of rats. Sudan black B staining was used to observe the fatty changes in liver. Immunohistochemical staining was used to observe the expression level of occludin protein in the intestinal epithelium. A real-time 16S rDNA PCR method was used to measure the number of escherichia coli, bacteroides and faecalibacterium prausnitzii in the feces of rats. Results: Model group had a higher serum levels of endotoxin (0.288 ± 0.045) and tumor necrosis factor (TNF)-α (1.07 ± 0.11) than the control group (0.192 ± 0.049, 0.94 ± 0.07) (P < 0.05). Berberine intervention had significantly reduced endotoxin (0.213 ± 0.025) and TNF-α level (0.93 ± 0.07) (P < 0.05). The expression level of occludin protein was significantly lower in the intestinal mucosa of model group than that of control group (0.166 ± 0.014), and berberine had promoted the expression of occludin protein in intestinal mucosa (0.055 ± 0.009), but the difference was not statistically significant (P > 0.05). At the same time, compared with the model group (7.29 ± 0.47), the number of bacteroidetes in the control group (9.49 ± 0.59) was decreased, while the number of bacteroidetes in the treatment group was increased (9.77 ± 0.87). The number of escherichia coli (6.92 ± 0.77) and faecalibacterium prausnitzii (8.70 ± 0.62) in the model group were increased than control group (5.42 ± 0.63, 9.49 ± 0.59), while the number of escherichia coli (6.34 ± 0.71) and faecalibacterium prausnitzii (9.77 ± 0.87) (P < 0.05) was reduced with the intervention of berberine. Conclusion: Berberine could effectively protect the intestinal barrier function in rats with NAFLD and the possible mechanism of action behind it may be the regulation of intestinal flora.

Characteristics, diagnostic and therapeutic strategies for chronic hepatitis B combined with non-alcoholic fatty liver disease

Presently, the situation of chronic hepatitis B combined with non-alcoholic fatty liver disease is relatively common in our country, and yet the relationship between them has not reached a consensus. The co-existing fatty liver may affect the efficacy of anti-HBV therapy and increase the all-cause mortality rates in patients. Therefore, it is very important to correctly diagnose and evaluate fatty liver changes, inflammation, and fibrosis for active prevention and treatment.

Understand the risk factors associated with non alcoholic fatty liver disease and changes in biochemical parameters in the patients: a prospective study

Background: The true prevalence of both NAFLD and NASH are elusive but estimates based on imaging and autopsy studies suggest that about 20-30% of the adults in United States and western countries have excess fat accumulation in the liver. About 10% of these, strictly speaking about 2-3% of the adult population fulfils the criteria of NASH. True prevalence of NAFLD in Indian patients is not known. So, this study was planned to look for current trend of NAFLD in Indian patients.Methods: This prospective observational study was conducted in the Department of Medicine on 65 patients with ultra-sonography finding of fatty liver disease with no history of alcohol, in one year study duration.Results: It is observed that maximum patients are of middle age from age 31-60 years comprising 76% of patients. Out of total patients, 34% and 66% were males and females respectively. Out of 65 patients, 45(69%) had obesity and maximum number of the patients had waist hip ratio and neck circumference more than the cut off value. Out of 65 patients, 19(29%) had hypercholesterolemia and 42(65%) had hyper-triglyceridemia. Out of 65 patients, 32(49%) had higher alanine transaminase (ALT) level and 17(29%) patients had higher AST level. Out of 65 patients, 29(45%) had the homeostasis model assessment of insulin resistance (HOMA-IR) less than cut off value (less than 2.25) and remaining 36(55%) were having HOMA-IR more than 2.25. The sensitivity for the cut off value for HOMA-IR is 72.7% and specificity is 49.1%.Conclusions: Obesity, neck circumference, and waist hip ratio are higher than its cut off value for both sex, insulin resistance evaluated through HOMA- IR directly relates to the causation of NAFLD but at some extents higher triglyceride levels are also associated but the values of ALT and AST levels did not give any clue in these cases of NAFLD.

Unripe Papaya (Carica papaya L.) Aqueous Extract (UPAE) for the acute toxicity test on fatty liver changes

We investigated whether the oral ingestion of aqueous extract of unripe papaya fruit (UPAE), would also induce fatty liver changes by analysing the UPAE-treated mice qualitatively. This study used laboratory experiments which performed by a proposed (new) recommended method with 11 subjects of female mice which were administered with single oral doses of 0; 50; 200; 400; 800; 1, 000; 1, 500; 2, 000; 3, 000; 4, 000; 5, 000 mg/kg respectively. All these mice were euthanized after 24 hours of UPAE administration. Histopathological studies were conducted using liver samples which were stained by Haematoxylin-Eosin (HE). The UPAE did not cause death in all doses but did induce hepatic steatosis and steatohepatitis at 4, 000 and 5, 000 mg/kg dosages. Ballooning degeneration, necroinflammation and portal fibrosis revealed at 200 – 5, 000 mg/kg. These findings suggest that the UPAE provoked the fatty liver changes at the highest dose administration. It may be obtained from a multiple hit process by the accumulation of the phytochemical compounds of UPAE.

Correlation of Ultrasonography Parameters with Tissue Transglutaminase Antibody Assay in the Diagnosis of Childhood Celiac Disease

Objective: The present study aimed to evaluate the potential benefits of ultrasonographic (USG) assessment in the diagnostic workup of children suspected of having celiac disease and its correlation with tissue transglutaminase (TTG) antibody assay. Materials and methods: A retro-prospective study, consisting 30 children with biopsy proven celiac disease diagnosis, was conducted. The tissue transglutaminase (tTG) assay was done on all the children, and further the children were subclassified based on the tTG titer values. The transabdominal sonography using convex (3-5 MHz) and linear (7-12 MHz) ultrasound probes was carried on the subjects, assessing the bowel lumen dimeter, bowel wall thickness, abnormal rugal folds count, presence of perihepatic fluid, fatty hepatic changes and mesenteric lymphadenopathy. Routine abdominal sonography was also carried out to complete the detailed evaluation of the abdomen. The sonographic bowel findings and the different classes of the tTG titers were correlated. Results: The median (IQR) age at onset of symptoms and at diagnosis was 6 (4-9) years. The median (IQR) value of blood tissue transglutaminase level (tTG) was 535 U/mL (63-7100), and most of the children belonged to class A (n=18, 60%) subclassification followed by class C (n=7, 23.3%) and class B (n=5, 16.6%). On sonological evaluation, the bowel abnormalities including bowel thickening was seen in 8 (26.6%) of the children, followed by the reduced jejunal folds and transient intussusception in the same frequency (n=5, 16.6%) and, hyper-peristalsis in 4 (13.3%) children. No dilated bowel loops were seen. Extra-intestinal observations like fatty liver changes, mesenteric lymphadenopathy, and peritoneal free fluid were noted in 23 (76.6%), 6 (20%), and 4 (13.3%) of the children respectively. Conclusion: Ultrasound is the most widely used first imaging tool in the evaluation of abdominal ailments. Multiple small bowel abnormalities are found in the celiac patients, which may vary according to the study population’s demographic and clinical features. More than half of the children with celiac disease showed small bowel abnormalities, and small bowel thickening, if present, may vary with the anti-tTg titer level. Multicentric and large size sample studies are required to accurately assess the association of serological antibodies titers with the bowel wall abnormality.

Iatrogenic pulmonary fat embolism after surgery in a patient with fatty liver

Introduction. Fat embolism refers to the presence of fat globules in the lung parenchyma and its peripheral circulation. Obstruction of the lung vessels by fat emboli can lead to acute cor pulmonale when the compensatory capabilities of the pulmonary vasculature are exceeded. Case report. We presented a case of a 78-year old man who suffered a dissection of abdominal aortic aneurysm. Urgent surgical procedure was performed and aneurysm replaced with aortobifemoral bypass grafting using a Dacron graft. Despite the procedure the patient died the following day. The autopsy revealed that the cause of death was hypovolemic shock. There were no bone fractures (also no fractures of ribs and sternum from cardiopulmonary resuscitation) or injuries of the subcutaneous fat tissue or other organs (besides those from the surgery). However, additional autopsy findings included fatty liver change, small liver hemorrhages (confirmed microscopically), as well as a presence of fat droplets in the hepatic veins, as well as in the pulmonary vessels, i.e. pulmonary fat embolism [confirmed with hematoxylin/ eosin (H/E), and Sudan III staining], which could be the contributing cause of death. Conclusion. The presented case indicates that pulmonary (or even systemic) fat embolism should be considered as the possible iatrogenic cause of unexpected and unexplained death in the cases where elective surgical procedures were performed in patients with fatty liver change. Pathologists must be aware of this possibility, since it is not easily recognized on routine H/E staining, and some of the special staining technique should be applied.

Relationship between liver controlled attenuation parameters and body fat mass and its distribution

Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson's correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ​​of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion: The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.

Aspartame and Sucralose-induced Fatty Changes in Rat Liver

To determine the cytoplasmic fatty change of rat liver due to artificial sweeteners - aspartame and sucralose. Experimental study. Department of Anatomy, King Edward Medical University, Lahore, in collaboration with the University of Veterinary and Animal Sciences Lahore, from May to October 2016. Adult Wistar albino rats were randomly divided into five groups. Group I was control group (animals were given drinking water by oral gavage). The animals of group II and III were given low (40 mg/kg body weight) and high dose (1000 mg/kg body weight) of aspartame, respectively. Animals of group IV and V were given low (5 mg/kg body weight) and high dose (1000 mg/kg body weight) of sucralose respectively by oral gavage. Doses were given once daily, six days a week for a total duration of 8 weeks. At the end of experiment, livers of all animal groups were observed for fatty change of cytoplasm. Artificial sweeteners cause cytoplasmic fatty change of varying degrees. This change was more marked in high dose group of aspartame (group III) as compared to low dose group (group II). In sucralose group, this change was seen only in high dose group (group V). Both artificial sweeteners-induced fatty changes in rat liver; the effect was least pronounced with low dose of sucralose.

37. Non-cranial large vessel vasculitis in a 65-year-old woman

IntroductionLarge-vessel vasculitis in older patients is typically associated with giant cell arteritis (GCA) usually presenting with cranial features. GCA can also present with a primarily extra-cranial pattern as large-vessel GCA (LV-GCA).Takayasu arteritis is a large-vessel vasculitis that affects younger females and classically involves the aorta and its major branches. This condition can clinically manifest with claudication of the extremities, impaired peripheral pulsation and systemic symptoms. Features of Takayasu arteritis and LV-GCA can overlap. This case reviews that of a 65-year-old lady with features of non-cranial large-vessel vasculitis and the approach taken to manage her case.Case descriptionA 65-year-old female developed pains affecting the shoulder and forearms over a period of weeks. She additionally noted pins and needles of the affected limbs. Symptoms were worse with use and consistent with claudication. She denied systemic symptoms, headache, visual changes or early morning stiffness.She was referred to the emergency department for assessment. Blood pressure could not be obtained and radial pulses were absent. She was subsequently arranged for further investigation via the vascular team. CT angiogram of the upper limbs demonstrated diffuse significant subclavian and axillary artery stenoses bilaterally with appearances deemed suggestive of underlying vasculitis.She was referred for rheumatological assessment. CRP was 50 and MRA aorta confirmed findings identified on CT scan. Prednisolone was initiated at a dose of 60mg daily for 4 weeks, and was subsequently decreased at an initial rate of 10mg every 2 weeks. Methotrexate was started at a dose of 15mg weekly.Inflammatory markers were noted to improve and CRP decreased to normal range. Despite this, although her paraesthesia resolved, she reported only a modest improvement of her upper limb claudication symptoms.Blood tests were monitored, however shortly after starting methotrexate, ALT significantly increased to 1002 IU/L. Autoimmune and viral hepatitis screen returned negative, US abdomen was suggestive of fatty liver changes but was otherwise unremarkable. Rise in ALT was attributed to methotrexate use and this was stopped, and levels improved. Mycophenolate was thus introduced as an alternative at a dose of 1g BD, but unfortunately resulted in recurrence of raised ALT.At present, she is being managed with prednisolone alone, of which is slowly being reduced. Her case is being additionally reviewed at our local vasculitis centre based at Hammersmith Hospital for consideration of tocilizumab should there be difficulties on steroid reduction.DiscussionTakayasu arteritis is a rare systemic large vessel vasculitis. Incidence is 1-2 per million annually with a female preponderance of 80-90%. Based on ACR classification criteria, the above patient would meet the diagnosis of this condition. Takayasu arteritis would normally be expected for those aged <40 years and has a median onset of 25-30 years. Due to her age, the diagnosis of large vessel vasculitis would be therefore be more consistent with LV- GCA, primarily in the absence of cranial features. Aorta and branch involvement can occur in up to 15% of GCA cases. Histologically, both GCA and Takayasu arteritis share similar findings and cannot be relied upon for diagnostic differentiation. Due to overlap of features, formal diagnostic labelling can be difficult in cases such as the one described.In regards to the management of her case, the general principle was taken of initial high dose prednisolone which has been gradually reduced. Introduction of DMARD therapy was implemented early which would be more typical for Takayasu arteritis rather than GCA. Unfortunately due to deranged ALT attributed initially to methotrexate, and subsequently mycophenolate, she is not currently on any steroid sparing treatment. Studies have demonstrated efficacy of IL-6 inhibition in managing large vessel vasculitis and as mentioned, her case is being reviewed with our local vasculitis centre for consideration of tocilizumab should there be difficulties on prednisolone weaning.Although CRP is now within normal range with treatment, our patient has ongoing claudication symptoms of the upper limbs. It is felt that this is likely due to residual vascular stenotic changes rather than current active vasculitis. As such, following stabilisation of her condition, consideration would be made for vascular surgical intervention in future.Key learning pointsDiagnosis of Takayasu versus giant cell arteritis can present a diagnostic challenge in some older patients due to overlap of typical features. The underlying process of large vessel vasculitis and shared components in both these conditions suggest they are within the same spectrum of disease. We discussed our management approach of high dose prednisolone which would be typically utilised in either diagnosis.In our case, due to drug induced hepatitis from methotrexate and subsequent mycophenolate, current management is with prednisolone alone. In regards to long term steroid sparing therapy, other options including IL-6 inhibition is being considered pending response to current treatment. Vascular surgical intervention for residual stenoses will also be reviewed following stabilisation of underlying inflammation.Conflicts of interestThe authors have declared no conflicts of interest.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Clinical validation of ultrasound backscatter statistics for the assessment of liver fibrosis

Introduction Deposition of fibrous tissue in the liver changes with the progression of liver cirrhosis. Ultrasound backscatter imaging may describe the scatterer distribution in the liver, and reflect the severity of liver cirrhosis. However, it is known that the backscatter statistics are often subject to ultrasound imaging settings, region of interest (ROI) for analysis and hepatic steatosis. This study aims to establish a standard imaging procedure and a discriminant model for assessment of liver fibrosis regardless of the degrees of liver fatty changes. Methods 201 patients received elective liver resection were prospectively enrolled in the study. Ultrasound radio-frequency (RF) data of right liver lobe through an intercostal space with the maximum imaging depth of 8cm were collected using the Terason t3000 ™ (convex array) system pre-operatively from each patient. Since significant inter-ROI variation was found when the ROI is less than 10 cm2, all the ROI's were selected such that the ROI area covered as much as possible the liver parenchyma and was larger than 10 cm2. The liver tissue was examined and determined by an experienced pathologist the degrees of liver fibrosis and fatty changes. Among the 201 patients, there were 36 F0, 51 F1, 26 F2, 22 F3 and 66 F4 patients while 62 with mild steatosis (5-30%) and 26 with severe steatosis (> 30%). A FDA-cleared backscatter analysis tool (AmCAD-USTM) was used to calculate the statistics and a stepwise logistic regression model was established to differentiate significant liver fibrosis (≥ F2). Results Three backscatter statistics, including the 95th percentile of the Nakagami (m) statistic, and the 75th and 95th percentiles of the histogram (h) statistics, were selected into the logistic model. Regardless of the liver fatty changes, the Receiver Operating Characteristic (ROC) curve analysis showed a significant discriminant power of the model for evaluation of liver fibrosis - stage 0 versus stage 1-4, AUC 0.77 (p-value Conclusions The liver fibrosis in human results in variation of the scatterer distributions in medical ultrasound imaging. Following a standard imaging procedure, a discriminant model is established and shown to be able to distinguish significantly different degrees of liver fibrosis regardless of the presence of steatosis.

Combined effects of E. Jambolana and C. zeylanicum extract in insulin resistance associated Structural and Functional Hepatic changes in high Fructose-fed rats

High fructose (HFr) dietary consumption is linked with insulin resistance (IR) and associated complications are documented in both animals and humans. The present study is to evaluate the combined effects of E. Jambolana and C. zeylanicum extracts in IR associated structural and functional hepatic changes in HFr fed rats. Male Wistar rats were randomly grouped into five (n=6). Group 1 received distilled water as normal control (NC), group 2 received HFr diet (60%w/v) as HFr control and group 3 received metformin (MET 500mg/kg), while group 4 received Jamun seed and cinnamon bark aqueous extracts (JSAE+CBAE 500mg/kg of each) and group 5 received Jamun seed and cinnamon bark ethanolic extracts (JSEE+CBEE 500mg/kg of each) respectively. All the rats except NC, fed with HFr diet for 42 consecutive days and respective treatments were administered orally, from day 28 onwards for the next 14 days while maintaining them on HFr diet. Physical and biochemical parameters such as fasting glucose, insulin, triglycerides (TG's), Serum Glutamic Pyruvate Transaminase (SGPT) and Oxaloacetic Transaminase (SGOT), Lactate Dehydrogenase (LDH) and C-reactive protein (CRP) and, Malondialdehyde (MDA) levels were measured. Liver histopathological studies were accessed for structural changes. HFr fed rats significantly (P<0.05) induced hyperglycemia, hypertriglyceridemia, hyperinsulinemia, and with impaired glucose tolerance evidenced by β-cell dysfunction and decreased insulin sensitivity (IS) indicates IR. HFr feeding had elevated hepatic markers, oxidative stress, and inflammation, altogether promotes fatty changes liver in IR rats. JSAE+CBAE and JSEE+CBEE groups significantly (P<0.05) reversed the aforementioned metabolic dysregularties and partially reversed fatty liver changes, and these results were comparable to MET. In conclusion, the combined effects of Jamun and cinnamon extracts exert antihyperglycemic, antitriglyceridemic, antioxidant, anti-inflammatory, and anti-steatosis properties in HFr fed rats. Thus, it offers a promising value in the management of IR associated hepatic changes.