Necroinflammatory Disease Research Articles

Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome.

Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.

Sinonasal Amoebiasis: An Unexpected Cause of Sinonasal Necroinflammatory Disease.

While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition. We identified sinonasal amoebiasis in 4 men, median age of 67 years (range: 37 to 71y). All were immunocompromised, including 2 with chronic lymphocytic leukemia, 1 with human immunodeficiency virus, and 1 with human immunodeficiency virus and kidney transplant. Patients presented with nasal mucosal necrosis or polypoid masses, with facial ulceration in 1 patient and distant dermal nodules in another. Biopsies displayed extensive necrotic debris and inflammation. Although amoebic cysts were abundant in 3 cases, they were mistaken for yeast at frozen section in 1 case; 1 case showed only rare trophozoites that were not recognized on initial biopsy. Periodic acid Schiff and Grocott Methenamine Silver stains highlighted the organisms, and polymerase chain reaction confirmed Acanthamoeba species in 3 cases tested. 2 patients responded well to antiprotozoal medications, but 2 died of disease. Overall, sinonasal amoebiasis presents as a necroinflammatory process in patients immunocompromised for various reasons. Amoebae can mimic other organisms or be incredibly scarce, requiring active consideration to recognize amoebiasis and differentiate it from overlapping conditions like invasive fungal sinusitis, granulomatosis with polyangiitis, and natural killer/T-cell lymphoma. Because sinonasal amoebiasis is highly treatable when diagnosed promptly, pathologists play a critical role in the recognition of this rare necroinflammatory disease.

Unconjugated hyperbilirubinemia may exacerbate certain underlying chronic liver diseases.

BACKGROUND: Negative correlations have been described between elevated serum unconjugated bilirubin levels and the prevalence/severity of various chronic inflammatory conditions. Whether a similar association exists for patients with unconjugated hyperbilirubinemia (UCB) and underlying chronic liver diseases (CLD) has yet to be reported. The aim of this study was to document hepatic necro-inflammatory disease activity and fibrosis in CLD patients with and without UCB and otherwise normal liver function tests (albumin and INR). METHODS: Necro-inflammatory disease activity was assessed by serum aminotransferase levels and fibrosis by APRI and FIB-4 calculations. UCB patients were matched 1:2 by age, gender, and underlying CLD to patients with normal bilirubin levels. RESULTS: From a database of 9,745 CLD patients, 208 (2.1%) had UCB and 399 served as matched controls. Overall, UCB patients had significantly higher serum aminotransferase levels, APRI, and FIB-4 scores. The differences were driven by patients with underlying chronic viral or immune mediated liver disorders rather than non-alcoholic fatty liver disease, alcohol-related liver disease, or 'other' CLDs. CONCLUSIONS: These results suggest UCB is associated with increased rather than decreased hepatic necro-inflammatory disease activity and fibrosis in patients with certain CLDs.

Hepatic copper accumulates in ferrets with and without hepatobiliary disease.

To determine hepatic copper concentrations and zonal distribution in ferrets with and without hepatobiliary disease, validate rhodanine-based qualitative copper scoring and digital copper quantification in ferret hepatic samples, and ascertain whether clinical features predicted copper accumulation. 34 ferrets, including 7 with necroinflammatory disease, 5 with hepatocellular carcinoma, 13 with non-necroinflammatory disease, and 9 with no hepatobiliary disease. Rhodanine-based digital copper quantification was validated by use of liver dually measured by atomic absorption spectroscopy and digital scanning (R2 = 0.98). Clinical features and hepatic copper scores and concentrations (dry weight liver) were compared between groups. Zonal copper distribution was determined. Hepatic copper concentration was strongly correlated with copper scores (ρ = 0.88). Ferrets with hepatobiliary disease were significantly older and had significantly higher serum alkaline phosphatase and γ-glutamyltransferase activities and creatinine concentrations. Centrilobular copper accumulated in 23 of 34 (64%) ferrets with (n = 15) and without (8) hepatobiliary disease. Median copper concentrations were not significantly different between ferrets with and without hepatobiliary disease but were significantly higher within neoplastic hepatic tissue in ferrets with hepatocellular carcinoma. Hepatic copper concentrations exceeded feline (> 180 µg/g) and canine (> 400 µg/g) reference limits in 19 and 9 ferrets, respectively. Hepatic copper > 1,000 µg/g occurred in 5 ferrets with and 2 without hepatobiliary disease. Clinical features did not predict copper accumulation. Rhodanine-based digital copper quantification and qualitative copper scoring discerned liver copper accumulation in ferrets. Ferrets with and without hepatobiliary disease displayed a propensity for centrilobular hepatic copper accumulation of uncertain clinical importance. Clinical and clinicopathologic features could not exclusively implicate pathologic copper accumulation.

STUDY OF CONCORDANCE BETWEEN THE DEGREE OF LIVER FIBROSIS ESTIMATED THROUGH APRI AND FIB-4 BIOCHEMICAL SCORES, AND ELASTORESONANCE IN PATIENTS WITH AUTOIMMUNE HEPATITIS

Autoimmune hepatitis is a chronic and progressive necroinflammatory disease with a fluctuating course of activity and affects more frequently the female sex. The etiopathogenesis is still unknown and may be the result of an interaction between factors: genetic, immunological, autoantigens; Therefore, the interaction of genetic predisposition with an environmental trigger and the disorder in immunoregulation would result in chronic inflammation of the hepatocytes and with it the development of hepatic fibrosis. Diagnostic tests for the evaluation of liver fibrosis include liver biopsy and non-invasive elastographic methods, such as transition elastography and elastoresonance, as well as serum biomarkers, composed of different variables that help predict the degree of liver fibrosis. Compare the concordance between the results obtained for the diagnosis of liver fibrosis by the APRI and FIB-4 score, with the elastoresonance, in patients with HAI. Elastoresonance, APRI and FIB-4 were performed in 6 patients to assess the concordance between different degrees of fibrosis. A total of 6 patients with a recent diagnosis of HAI were included in the study. The mean age was 50.33 years and 100% were women. 66.66% of the patients presented an advanced degree of fibrosis (F2-F3-F4) due to elastoresonance. The values ​​for the APRI index were: 3 patients (50%) had an advanced degree of fibrosis, 1 patient had a low degree of fibrosis (6%) and 2 patients (33.33%) had intermediate. The findings for the FIB-4 values ​​were exactly the same. The agreement of elastoresonance in the different degrees of fibrosis against the APRI and FIB-4 score was 100%. Non-invasive methods to measure the degree of liver fibrosis in patients with chronic liver disease have shown to be useful, and in this study, it transcends that the correlation with the degree of fibrosis obtained by elastoresonance with the APRI and FIB-4 scores is 100%, this could avoid reaching the liver biopsy, which although it is the gold standard in measuring the degree of liver fibrosis, is an invasive and expensive method, which involves risks for the patient (puncture of other internal organs, infection and adverse reaction to contrast material). In patients classified with advanced fibrosis, the concordance between the estimates obtained using the elastoMR and those derived from the APRI and FIB-4 scores are high. However, a limitation of this study is the size of the sample. The authors declare that there is no conflict of interest.

Ferroptosis: A Trigger of Proinflammatory State Progression to Immunogenicity in Necroinflammatory Disease.

Until recently, necrosis is generally regarded as traumatic cell death due to mechanical shear stress or other physicochemical factors, while apoptosis is commonly thought to be programmed cell death, which is silent to immunological response. Actually, multiple modalities of cell death are programmed to maintain systematic immunity. Programmed necrosis, such as necrosis, pyroptosis, and ferroptosis, are inherently more immunogenic than apoptosis. Programmed necrosis leads to the release of inflammatory cytokines, defined as danger-associated molecular patterns (DAMPs), resulting in a necroinflammatory response, which can drive the proinflammatory state under certain biological circumstances. Ferroptosis as a newly discovered non-apoptotic form of cell death, is characterized by excessive lipid peroxidation and overload iron, which occurs in cancer, neurodegeneration, immune and inflammatory diseases, as well as ischemia/reperfusion (I/R) injury. It is triggered by a surplus of reactive oxygen species (ROS) induced in an imbalanced redox reaction due to the decrease in glutathione synthesis and inaction of enzyme glutathione peroxidase 4 (GPX4). Ferroptosis is considered as a potential therapeutic and molecular target for the treatment of necroinflammatory disease, and further investigation into the underlying pathophysiological characteristics and molecular mechanisms implicated may lay the foundations for an interventional therapeutic strategy. This review aims to demonstrate the key roles of ferroptosis in the development of necroinflammatory diseases, the major regulatory mechanisms involved, and its potential as a therapeutic target.

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity. In experimental autoimmune hepatitis (EAH), hepatic accumulation of mature cDCs was observed, along with an increase in the periphery. Sequentially, bone marrow-derived dendritic cells (BMDC) from EAH mice exhibit more proinflammatory function than those from control mice. In vitro, ConA treatment promotes the maturation of BMDCs, which are characterized by higher expression of MHC-II, costimulatory molecules and cytokine secretion. ConA also induced the expression of autophagy-related protein and the formation of autophagosomes in DCs. To further investigate whether ConA-induced DC activation is associated with autophagy, we utilized 3-MA and bafilomycin A1 to block autophagy flux and accessed the maturation and function of DCs induced by ConA. 3-MA and bafilomycin A1 inhibited the mature status and proinflammatory cytokine secretion and diminished the proliferation and differentiation of CD4+ T cells when ConA-induced BMDCs cocultured CD4+ T cells. We demonstrated that cDCs contribute to the pathogenesis of AIH through excessive maturation. Aberrant autophagy flux plays a vital role in the immunogenic maturation of cDCs in AIH, and tolerogenic cDCs by inhibition of autophagy flux can be exploited as a new therapeutic approach for AIH.

Creatinine Phosphokinase (CPK) Elevation in the Coexistence of Wilson's Disease and Autoimmune Hepatitis with Atypical Presentation: A Diagnostic Dilemma

Background: Wilson's disease (WD) is a genetic disorder with various clinical presentations due to excessive accumulation of copper in the liver and other organs. It can present as acute/chronic hepatitis, liver failure, extrahepatic and neuromuscular manifestations. Autoimmune hepatitis (AIH) is a necroinflammatory disease of the liver, which affects a lot of people particularly the children population. AIH has a broad clinical presentation that is similar to WD. Coexistence of WD with elevated creatinine phosphokinase (CPK) and AIH, may be a diagnostic dilemma. Case Report: We presented a 6 years old boy with dysarthria, aggressive behavior, weak attention, concentration and weight loss with abnormal physical examination. Laboratory, histochemical, genomic studies, muscle/liver biopsy and atomic absorption test confirmed the diagnosis of both WD and AIH in the boy. Conclusion Although CPK and liver enzyme elevation is a rare presentation of chronic hepatitis with dominant feature of WD and AIH; however, simultaneous therapy with immunosuppressive drugs and Penicillamine may have superior benefit with a significant response.

Necrotic amplification loop in acute pancreatitis: pancreatic stellate cells and nitric oxide are important players in the development of the disease

Necrotic amplification loop in acute pancreatitis: pancreatic stellate cells and nitric oxide are important players in the development of the disease

Acalculous cholecystitis: Three Case Reports

Acute acalculous cholecystitis is an acute necroinflammatory disease of the gallbladder. Whilst acalculous cholecystitis accounts for approximately 10 percent of acute cholecystitis cases it is associated with a high morbidity and mortality.The condition rapidly progresses to complications such as gangrene, perforation and empyema of the gallbladder. Gangrenous cholecystitis is the most severe form and complication of acute cholecystitis. Acute acalculous cholecystitis warrants urgent surgical intervention to prevent catastrophic outcomes. We report a series of three patients that we managed for acute acalculous cholecystitis. The first patient was a 65-year-old, male who was positive of Human Immunodeficiency Virus (HIV) with a CD4 count of 165 cells/mm3 and was on antiretroviral treatment. The second patient was a 73-year-old male with no comorbidities. The last patient was a 72-year-old female with congestive cardiac failure due to hypertension. One patient had a successful laparoscopic cholecystectomy and the other two had open cholecystectomies. Two of the patients did well and were discharged whilst the third patient died in intensive care unit day 2 postoperatively. All the three patients had no evidence of gallbladder stones. Two of the histology reports confirmed acalculous gangrenous cholecystitis and the third histology showed acalculous haemorrhagic cholecystitis. Acalculous cholecystitis is a surgical emergency. Once suspected, principles of management include resuscitation, hospital admission, broad spectrum antibiotics, adequate analgesia and emergency surgery.Key words: Acalculous cholecystitis, Gangrenous cholecystitis, Cholecystectomy

The MET Receptor Tyrosine Kinase Confers Repair of Murine Pancreatic Acinar Cells following Acute and Chronic Injury.

Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury.

Functional Immune Anatomy of the Liver-As an Allograft.

The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenicproperties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system.

The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease

BackgroundTao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine that has been used for centuries in the treatment of Chinese patients with chronic liver disease. Recently, THSWD has been reported to alter vascular endothelial growth factor (VEGF) induced angiogenesis, raising the possibility that in addition to its anti-inflammatory properties; THSWD might also inhibit hepatic blood flow associated fibrosis. AimTo document the effects of THSWD on hepatic necroinflammatory disease activity, fibrosis and VEGF signaling in a murine model of chronic liver disease. MethodsSixty adult mice were equally divided into six study groups. Five groups were exposed to subcutaneous carbon tetrachloride (0.1ml/10g BW) for six weeks. Three of the five groups were treated with different concentrations of THSWD (4.25, 8.50, 17.00g/kg), one with 0.1mg/kg of Colchicine (positive control), and one with physiologic saline (negative control). Mice in the sixth group were not exposed to CCl4 and remained untreated (healthy controls). Liver enzymes/function tests, hyaluronic acid and laminin levels were measured in serum, and hepatic histology, VEGF, Flt-1 and kinase insert domain-containing receptor (KDR), Akt and phosphorylated Akt (pAkt) expression were documented in liver tissue at the end of treatment. ResultsHepatic necroinflammatory disease activity and fibrosis were significantly attenuated in THSWD treated mice in a dose dependent manner. These beneficial results were similar and often exceeded those achieved with Colchicine. In addition, VEGF, Flt-1, KDR, Akt and pAkt mRNA and protein expression were reduced in TSHWD treated mice. ConclusionsIn this animal model of chronic liver disease, THSWD decreased hepatic necroinflammatory disease and fibrosis. Inhibition of VEGF expression and downstream signaling were associated with these findings. Further studies with this and other TCMs as treatment for chronic liver disease are warranted.

Alcoholic pancreatitis: New insights into the pathogenesis and treatment.

Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.

Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis.

Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100μg/kg) and sequential LPS (10mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1×10(6)/head) were infused on 24h after LPS injection via the tail vein. The rats were sacrificed 3days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP.

Acinar cell-specific knockout of the PTHrP gene decreases the proinflammatory and profibrotic responses in pancreatitis

Pancreatitis is a necroinflammatory disease with acute and chronic manifestations. Accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic pancreatitis (CP). Pancreatic parathyroid hormone-related protein (PTHrP) levels are elevated in a mouse model of cerulein-induced AP. Here, we show elevated PTHrP levels in mouse models of pancreatitis induced by chronic cerulein administration and pancreatic duct ligation. Because acinar cells play a major role in the pathophysiology of pancreatitis, mice with acinar cell-specific targeted disruption of the Pthrp gene (PTHrP(Δacinar)) were generated to assess the role of acinar cell-secreted PTHrP in pancreatitis. These mice were generated using Cre-LoxP technology and the acinar cell-specific elastase promoter. PTHrP(Δacinar) exerted protective effects in cerulein and pancreatic duct ligation models, evident as decreased edema, histological damage, amylase secretion, pancreatic stellate cell (PSC) activation, and extracellular matrix deposition. Treating acinar cells in vitro with cerulein increased IL-6 expression and NF-κB activity; these effects were attenuated in PTHrP(Δacinar) cells, as were the cerulein- and carbachol-induced elevations in amylase secretion. The cerulein-induced upregulation of procollagen I expression was lost in PSCs from PTHrP(Δacinar) mice. PTHrP immunostaining was elevated in human CP sections. The cerulein-induced upregulation of IL-6 and ICAM-1 (human acinar cells) and procollagen I (human PSCs) was suppressed by pretreatment with the PTH1R antagonist, PTHrP (7-34). These findings establish PTHrP as a novel mediator of inflammation and fibrosis associated with CP. Acinar cell-secreted PTHrP modulates acinar cell function via its effects on proinflammatory cytokine release and functions via a paracrine pathway to activate PSCs.

The effect of erythropoietin to pulmonary injury and mast cells secondary to acute pancreatitis.

BackgroundAcute pancreatitis is a life-threatening necroinflammatory disease that is characterized by systemic inflammatory response syndrome and acute lung injury even in its very first days. Erythropoietin (EPO) is a hormone considered as an antiapoptotic and cytoprotective with observed receptors of anti-inflammatory effect on organs apart from the liver and the kidneys. In this study, the effects of EPO on pulmonary mast cells and on secondary injury caused by acute pancreatitis are investigated.MethodsTwenty one Wistar Albino rats were divided into three groups—sham, control, and EPO groups—with 7 rats per group. Pancreatitis was induced by administering 4.5% sodium taurocholate into the pancreatic duct. A 1000 U/kg/day dosage (three times) of EPO was administered to the EPO group. Blood urea nitrogen (BUN), creatinine, amylase, and troponin I in the serum were studied; and lung, kidney, brain, and heart tissues were examined histopathologically.ResultsThere were no histopathological changes in the other organ tissues except for the lung tissue. Compared to the control group, the EPO group showed significantly reduced alveolar hemorrhage, septal neutrophil infiltration, lung wall thickness score, and mast cell count in the lung tissue.ConclusionsAdministration of EPO reduces the mast cell count and lung wall thickness, and it reduces the alveolar hemorrhage and septal infiltration induced by acute pancreatitis.

Acute Gangrenous Acalculous Cholecystitis In An Adolescent: A Case Report

Introduction: Acute Acalculous cholecystitis (AAC) represents a severe complicated variant of acute gallbladder (GB) disease. AAC most often occurs in old age, critically ill patients, especially related to trauma, surgery, shock, burns, sepsis, total parenteral nutrition, diabetes, immunosupression and/or prolonged fasting. The presentation of acalculous cholecystitis is similar to that of calculous disease. Case Report: An 18 year old male patient presented with severe abdominal pain associated with tenderness and guarding in right hypochondrium and epigastric region. Radiological investigations were suggestive of acute acalculous cholecystitis. Cholecystectomy was performed subsequently. Discussion: AAC is defined as an acute necroinflammatory disease of the gallbladder in the absence of cholelithiasis. The etiology of AAC is multifactorial and likely results from bile stasis or ischemia or both. Ultrasonography (USG) is considered as first modality to evaluate suspected AAC and diagnostic triad is GB wall thickness, sludge, and hydrops. Computed Tomography (CT) scan can be performed if other abdominal pathology is considered more likely. Treatment options for AAC are cholecystostomy and cholecystectomy. Cholecystectomy generally is considered the definitive therapy. Cholecystostomy can be a lifesaving alternative in the patient considered too unstable to undergo definitive surgery. Conclusion: The possibility of AAC, especially in a younger patient with symptoms of acute cholecystitis should always be considered, in spite of the absence of any medical co morbid condition and risk factors. Proper clinical assessment and interpretation of investigation with high index of suspicion with timely intervention can reduce mortality and morbidity associated with AAC. Key word: Acute Acalculous cholecystitis (AAC), Adolescent, risk factor.

Hepatic Injury Correlates With Apoptosis, Regeneration, and Nitric Oxide Synthase Expression in Canine Chronic Liver Disease

Assessment of the clinical severity, pathogenesis, and prognosis of canine chronic liver disease poses significant challenges to clinicians and pathologists, relating in part to a lack of standardized terminology and assessment methods and also to a lack of understanding of the pathogenesis of chronic liver disease in the dog. This study graded the severity of necroinflammatory activity in chronic liver disease in dogs using a modification of Ishak's grading scheme for human chronic liver disease and examined the association of grade score with hepatocellular apoptosis, regeneration, nitric oxide synthase isoform expression, copper and iron accumulation, and indicators of oxidative stress. Formalin-fixed, paraffin-embedded hematoxylin and eosin (HE)-stained liver biopsies from 45 dogs with chronic liver disease and 55 healthy control dogs were graded for various morphologic components of liver injury and response. The cumulative score for grade of necroinflammatory activity was strongly and significantly correlated with immunoreactive labels for hepatocellular proliferation (Ki-67); apoptosis (cleaved caspase-3); inducible nitric oxide synthase (iNOS) in lobular, portal, and septal stromal cells; endothelial nitric oxide synthase (eNOS) in hepatocytes and lobular, portal, and septal stromal cells; and total stainable hepatic iron. A weaker significant correlation was found between grade and accumulation of hepatocellular copper. No significant correlation was found between grade and immunoreactivity for malondialdehyde-protein adducts. These results document a method for grading of the severity of necroinflammatory disease in canine liver biopsies and show an association with increased iNOS and eNOS expression.

Impact of hepatitis C virus co-infection on HIV patients before and after highly active antiretroviral therapy: an immunological and clinical chemistry observation, Addis Ababa, Ethiopia.

BackgroundHepatitis C virus (HCV) is an RNA virus which has been known to cause acute and chronic necro-inflammatory disease of the liver. It is the leading cause of end-stage liver disease and hepatocellular carcinoma. HIV is known to have a negative impact on the natural disease outcome and immune response of HCV infection, whereas the reverse remains unclear. We evaluated the impact of HCV co-infection on recovery of CD4+ and CD8+ T-cells and liver enzyme levels before and after initiation of highly active antiretroviral therapy (HAART) in HIV/HCV co-infected patients.MethodsA hospital-based, observational, prospective cohort study design was used for this study. Pre-antiretroviral treatment (Pre-ART) and under HAART HIV mono-infected and HCV/HIV co-infected individuals who are under regular follow-up were recruited for this study. 387 blood samples were collected from volunteer, known HIV positive Ethiopian patients and screened for HCV. Twenty five HCV/HIV co-infected patients were prospectively followed for four years. CD4+ and CD8+ T-cells and liver enzyme levels were determined annually for each of the participant.ResultsThe prevalence of HCV/HIV co-infection in this study was 6.5%. Both HCV/HIV co-infected and HIV mono-infected under HAART groups showed CD4+ recovery (343 Vs 426; P < 0.004, OR = 4.97, 95% CI = 2.41 to 10.27) respectively; but, the recovery rate was higher in mono-infected (80 Vs 426) than co-infected group (148 Vs 343). The recovery and/or decline pattern of CD8+ T-cells was the same with that of CD4+. In 75% of co-infected groups, the mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were above the upper limit of normal reference range. Analyses restricted to individuals who initiated HAART and pre-ART showed similar results.ConclusionWe found that CD4+ T-cell recovery was negatively affected by the presence of ongoing HCV replication in under HAART co-infected individuals and fast decline of CD4+ T-cells in pre-ART patients. It was also associated with increased ALT and AST enzyme levels in both HAART initiated and treatment naïve co-infected patients.