Spotty Necrosis Research Articles

Histologic Patterns of Ribociclib-induced Liver Injury

Abstract Introduction/Objective Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment. Methods/Case Report Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns. Results (if a Case Study enter NA) The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2). Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib. Conclusion Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.

S2867 Turmeric-Induced Hepatitis

Introduction: Dietary supplementation use has been on an exponential rise for the past few years. Turmeric is one of the most used, with curcumin being its major active ingredient. Recently, cases of turmeric induced autoimmune hepatitis as well as herbal induced liver injury (HILI) have been documented. We present a case of turmeric induced hepatotoxicity in a 64-year-old female. Case Description/Methods: A 64-year-old female with a history of hypertension, presents with jaundice and abdominal discomfort. Vitals were normal. Exam showed scleral icterus with an unremarkable abdominal exam. Lab findings revealed a normal CBC, INR, and a negative blood alcohol level, a total bilirubin of 13.6 mg/dl with a direct bilirubin of 9.2 mg/dl, an ALP of 248 IUnits/L, a GGT of 616 Units/L, an AST of 2789 IUnits/L, and an ALT of 3296 IUnits/L. Hepatitis panel with HEV were negative. ANA, AMA, ASMA, tTg antibody, Ig levels, TSH, and T4 were all negative or within normal limits. Patient had a normal iron saturation, negative ceruloplasmin, Tylenol and ASA levels. COVID19 PCR test was negative. CT abdomen/pelvis was non-diagnostic. An EGD/EUS/ERCP showed a mildly thickened gallbladder wall. Liver biopsy showed portal and lobular hepatitis with spotty necrosis, without evidence of an autoimmune process, suggesting a drug induced liver injury. Patient then admitted to the use of turmeric in the past 3-4 weeks. Turmeric was discontinued and patient’s lab values normalized within 1 month. Discussion: Turmeric has been used for thousands of years as a spice, and has been linked to antioxidant, anti-inflammatory and anti-cancer effects. Clinical studies have popularized its use for patients with immune disorders such as autoimmune thyroiditis, and rheumatoid arthritis, despite the associated risk of autoimmune hepatitis in such patients. Curcumin is the major active ingredient in turmeric, however when taken alone, it has a poor bioavailability, with extensive 1st pass metabolism. Turmeric contains Piperine (a black pepper extract), that augments and increases curcumin doses up to 2000-fold by inhibiting hepatic drug-metabolizing enzymes. Multiple RCTs have studied the safety of curcumin showing minimal side effects. In 2013, HILI accounted for 20% of drug-induced liver injury cases. Liver enzymes resolve within 1 month of discontinuation. Due to turmeric’s possible increased risk for hepatotoxicity, clinicians should highlight this to their patients and make them aware of the potential risks that exist when using turmeric.Figure 1.: 400x H&E stain): The portal areas are expanded by predominantly lymphocytic inflammation with scattered eosinophils and rare plasma cells. Figure 2 (400 x PAS): There is spotty necrosis. There is no steatosis, ballooned hepatocytes, granulomas, or viropathic changes. Figure 3 (400x): The Reticulum stain shows a mild increase in portal/periportal fibrosis.Table 1.: RUCAM (Roussel Uclaf Causality Assessment Method) Score: Method for detecting drug-induced liver injury or herb-induced liver/hepatocellular injury (modified) ALT: Alanine Transaminase, AST: Aspartate Transaminase, EBV: Epstein-Barr Virus, HSV: Herpes Simplex Virus, VZV: Varicella-Zoster Virus, PSC: Primary Sclerosing Cholangitis.

Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies.

The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. During the follow-up period (median, 252days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

A very fruitful liver – hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Hepatic glycogenosis (HG) is an underrecognised hepatic pathology of diabetes with excess glycogen deposition in the hepatocytes as a result of hyperglycaemia and large doses of insulin administration in type 1 diabetes. This case study reports a 25-year-old female with a constellation of nonspecific symptoms including lethargy, tremors, diaphoresis, and generalized abdominal pain. This in on a background of anti-IA2 antibody positive type 1 diabetes with a HbA1c of 8.9%. The patient also had a persistently elevated lactate level in the absence of sepsis or abdominal pathology. Core liver biopsy showed macrovesicular steatosis, hepatocytes with granular cytoplasm and pseudo inclusions, which stained PAS-positive for glycogen. The hepatocytes also showed features of megamitochondria. Focal lobular inflammation was seen associated with spotty necrosis in one focus. HG arises from disruption of the normal balance between glycogenesis and glycogenolysis, leading to trapping of glycogen within the hepatocytes. This leads to hepatomegaly and consequent liver damage which becomes evident with blood release of aminotransferases.

Correlation between viral load, histopathologic necroinflammatory grade and fibrotic stage in viral hepatitis

Introduction: Liver needle biopsy and histopathology of liver parenchyma are one of the most accurate methods for assessing the severity of inflammation and fibrosis in these patients, which is based on Knodell’s standard system. Objectives: The aim of this study was to investigate the relationship between viral load of hepatitis B and C in polymerase chain reaction (PCR) with pathologic necroinflammatory grade and fibrotic stage of hepatitis in liver biopsy. Patients and Methods: Pathologic evaluation performed to determine the grade and stage of viral hepatitis by using 5μ sections stained with hematoxylin-eosin, Masson trichrome and reticulin in unique center. Data were analyzed using SPSS 16 software. Results: There was a significant relationship between viral load and grade of hepatitis B and C. No association was found between viral load of hepatitis B and C and fibrotic stage of hepatitis. Additionally, relationship between spotty necrosis and portal inflammation with viral load of hepatitis B and relationship between periportal interface hepatitis and viral load of hepatitis C were statistically significant. Conclusion: Despite the association between viral load in PCR and necroinflammatory grade in the histopathology of liver needle biopsy, the relationship between viral load and fibrotic stage is rejected, which can be affected by the duration of the disease.

Histological Patterns of Hepatitis and Cholangitis

Histological Patterns of Hepatitis and Cholangitis

The Effect of Stress Using Long-Term Continuous LightExposure on Liver Cells in Male and Female Wistar Rats

AbstractBackground: Many modern lifestyles are unhealthy andcan negatively affect our health. Many studies showed thatthe stress caused pronounced action on the structure of variousbody systems. The liver is one of the body organs that can beheavily affected by stress. The liver can withstand stress forlonger periods and shows signs of damage very late althoughthe structural changes can be detected very early.Aim of Study: Is to examine the acute and chronic effect of acute and chronic stress of long-term continuous light exposure on the structure of the liver tissues.Material and Methods: 48 male and female Wistar rats (250-300g) were enrolled in 6 groups (n=8/group). Group (a);Normal male control group with normal light/dark exposure.Group (b); Normal female control group with normal light/darkexposure. Group (c); Continuous room light for 3 weeks malegroup as an acute stress model in which normally fed malerats exposed to continuous room light exposure for 3 weeks.Group (d); Continuous room light for 3 weeks female groupas an acute stress model in which normally fed female ratsexposed to continuous room light exposure for 3 weeks.Group (e); Continuous room light for 3 months male groupas a chronic stress model in which normally fed male ratsexposed to continuous light exposure for 3 months. Group (f); Continuous room light for 3 months female group as achronic stress model in which normally fed female rats exposed to continuous light exposure for 3 months.Results: Sections of liver tissues of the groups who livedunder acute stress showed generally, preserved hepatic archi-tecture. The hepatocytes showed marked ballooning (vacuolardegeneration). The sinusoids and central veins showed con-gestion. Sections of liver tissues of the groups who livedunder chronic stress conditions showed in general, preservedhepatic architecture. The hepatocytes showed ballooning (vacuolar degeneration), focal spotty necrosis, together withsome binucleated cells. The sinusoids & central vein showedcongestion.Conclusion: This study used 48 Wistar mice as a modelto assess the effect of stress on liver tissues. Continuous roomlight exposure was used as acute stress for 3 weeks and aschronic stress for 3 months. This stressful stimulus and its deleterious effect on the liver may be supported by the theoryof sympathetic nervous system overactivity. The examinedliver tissues in this study showed congestive and degenerativechanges both in acute and chronic stressed animals. Changingmodern lifestyles to one that respects the natural chronobiologyis important for our wellbeing.

Arctiin antagonizes triptolide-induced renal toxicity in rats via anti-inflammatory pathway

To investigate the protective effect of arctiin with anti-inflammatory bioactivity against triptolide-induced nephrotoxicity in rats and explore the underlying mechanism. Forty SD rats were divided into 4 groups for gastric lavage of normal saline, arctiin (500 mg/kg), triptolide (500 μg/kg), or both arctiin (500 mg/kg) and triptolide (500 μg/kg). Blood samples were collected for analysis of biochemical renal parameters, and the renal tissues were harvested for determining the kidney index and for pathological evaluation with HE staining. In the in vitro experiment, HK-2 cells were treated with arctiin and triptolide either alone or in combination, and the cell viability was determined with MTT assay; the cell morphological changes was observed using laser confocal microscopy, cell apoptosis was detected using flow cytometry, and the expressions of inflammation-related protein expression were detected by Western blotting. In SD rats, arctiin significantly antagonized triptolide-induced elevation of BUN, Scr and kidney index (P < 0.05) and obviously improved renal tissue damages induced by triptolide including cell swelling, vacuolization and spotty necrosis. Arctiin significantly inhibited triptolide-induced cytotoxicity in HK-2 cells and increased the cell viability at 24 h (P < 0.05). Arctiin also attenuated triptolide-induced cell morphological changes, decreased cell apoptosis rate (P < 0.05) and reversed the expressions of IκBα and nuclear p65 (P < 0.05). Arctiin can protect the kidney from triptolide-induced damages in rats possibly through the anti-inflammatory pathway.

Mutations in Myosin 5B in Children With Early-onset Cholestasis.

Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 μmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.

Cytochrome P450 Enzyme-Mediated Bioactivation as an Underlying Mechanism of Columbin-Induced Hepatotoxicity.

Columbin, a furanoid compound, is the major bioactive ingredient of Tinospora sagittata (Oliv.) Gagnep, a traditional Chinese medicine that has been reported to cause liver injury in the clinic. The aim of this study was to investigate the hepatotoxicity caused by columbin and its underlying mechanism. Our results indicated that columbin could result in a dose-dependent increase of mice serum alanine aminotransferase and aspartate aminotransferase after oral treatment with columbin, as well as local spotty necrosis in the liver of mice treated with columbin. No hepatotoxicity was observed in mouse treated with the same dose of tetrahydrocolumbin. Pretreatment with ketoconazole preserved the mice from columbin-induced hepatotoxicity. Further studies suggested that bioactivation of the furan ring played an indispensable role in columbin-caused hepatotoxicity. In vitro and in vivo metabolism studies demonstrated that columbin could be metabolized into the cis-butene-1,4-dial intermediate, which readily reacted with glutathione and N-acetyllysine to form stable adducts. Ketoconazole displayed strong inhibitory effect on the generation of M4 and M5 both in vitro and in vivo. Further recombinant human CYP450 screening demonstrated that CYP3A4 was the major enzyme responsible for columbin bioactivation. The present study demonstrated that columbin was hepatotoxic and CYP3A4-mediated bioactivation of the furan ring would serve as an underlying mechanism for columbin-induced hepatotoxicity.

Histopathological features of chronic hepatitis B reactivation

It was aimed to investigate histopathological changes in acute hepatic exacerbations. A total of 20 patients, who developed acute hepatic exacerbation on the base of chronic hepatitis B infection, were enrolled in the study and liver biopsy was performed. Histological activity index (HAI) and its components, fibrosis scores and total HAI score were calculated according to the Ishak scoring system. All of the patients enrolled in the study had portal inflammation and spotty necrosis. Fibrosis was present in 17 patients. The median grade, stage and total HAI scores of the patients were 7 (2-14), 2 (0-3) and 8.5 (4-16), respectively. Positive correlation was determined between necroinflammation and ALT. While grade and total HAI score did not show significant difference among genders, fibrosis was significantly higher in males (p=0.008). The findings of this study showed that there are significant correlation between histopathologic changes (grade and total HAI score) in liver biopsy and plasma ALT, AST and Total bilirubin levels during acute hepatic exacerbation in patients with chronic hepatitis B infection.

Effects of Sodium Selenite on Oxidative Damage in the Liver, Kidney and Brain in a Selenite Cataract Rat Model

Selenite cataracts are effective and convenient animal models for simulation of human senile nuclear cataracts. These models are widely used to study the effects of various stresses on eye lenses and to screen anticataract drugs. However, there have been no comprehensive toxicological evaluations of these animal models. To investigate the effects of sodium selenite on some important organs in selenite cataract model animals, this study analyzed (1) histopathology by hematoxylin and eosin (H&E) staining; (2) methionine sulfoxide reductase (Msr) A and B1 protein expression; (3) glutathione peroxidase (GPx), thioredoxin reductase (TrxR) and superoxide dismutase (SOD) activity; and (4) malondialdehyde (MDA) levels in the liver, kidney, and brain in a selenite cataract rat model. The results showed that sodium selenite induced severe oxidative damage, especially in the hippocampus and corpus striatum of the brain, in Sprague-Dawley (SD) rats. This damage was evidenced by mild gliocyte proliferation, significant disorder of neuronal arrangement with acidophilic changes in the hippocampus, and significant occurrence of focal microglia or lymphocytic infiltration in the corpus striatum after selenite injection for cataract simulation. The damage was closely related to significant decreases in antioxidant enzyme expression and activity and significant increases in lipid peroxidation (MDA) levels. Furthermore, nonsignificant swelling and scattered spotty necrosis were observed in the liver. These results imply that physiological changes in model animals should be considered when carrying out anticataract drug screening and that pathological changes in other nontarget organs should be prevented.

U50488H improves organ function after septic shock

Objective To investigate the effect of U50488H on the ultrastructure and organ function in septic shock rats. Methods Forty SD male rats were randomly(random number) divided into 5 groups: sham group, septic shock group, U50488H+septic shock group, nor-BNI+U50488H+septic shock group, and nor-BNI+septic shock group, with 8 rats in each group. Cecal ligation and puncture (CLP) was performed to induce septic shock in the septic shock group. Rats in the U50488H+septic shock group were treated with U50488H injection by intravenous at the shock point, and other procedures were the same as the septic shock group. Rats in the nor-BNI+U50488H+septic shock group were treated with nor-BNI injection by intravenous 3.5 h after abdomen closed, and other procedures were the same as the U50488H+septic shock group. Except for U50488H injection, rats in the nor-BNI+septic shock group received procedures the same as the nor-BNI+U50488H+septic shock group. Albumin, cardiac troponin I (cTnI) and N terminal pro B type natriuretic peptide (NT-proBNP) in serum were measured at abdomen-closed, 3, 6, and 12 h after CLP. The changes of histology and ultramicro structure under electron microscope of lung, heart, liver and kidney of rats were observed at 12 h after CLP. Statistical analysis was performed using SPSS 19.0. Comparison among groups was carried out using ANOVA, and Student’s t-test was used for multiple comparisons as post-hoc. Results At 6 and 12 h of CLP, serum albumin of the septic shock group were significantly lower than those of the sham group (P<0.01), while those in the cTnI and NT-pro BNP groups were higher at 3, 6, and 12 h of CLP (P<0.01). Compared with the septic shock group, serum albumin of the U50488H+septic shock group increased significantly (P<0.01), whereas the serum levels of cTnI and NT-pro BNP decreased remarkably at 3, 6 and 12 h of CLP (P<0.05, P<0.01, respectively). Compared with the sham group, the alveolar wall was severely damaged, the alveolar septum and blood vessel wall were thickened obviously; the myocardial fiber was swollen, necrotic, and the infiltration of central granulocyte was increased significantly; hepatocyte showed edema, vacuolar-like steatosis, fatty degeneration, spotty and focal necrosis; and slight edema and vacuolar degeneration were found in the glomerulus endothelial in the septic shock group. Compared with the septic shock group, the ultrastructural damage of the lung, heart, liver and kidney of the U50488H+ septic shock group was significantly improved. All the above effects of U50488H could be blocked by nor-BNI (a selective κ-opioid receptor antagonist) (P<0.01). Conclusions U50488H can promote the recovery of serum albumin, and protect organ function in septic shock rats. Key words: U50488H; Septic shock; Organ function; Ultrastructure

A Toxoplasma gondii strain isolated in Okinawa, Japan shows high virulence in Microminipigs

Toxoplasma gondii strains have been isolated all over the world and their virulence has been examined mainly using laboratory mice. However, T. gondii differs in virulence depending on the host animal species. Therefore, to evaluate the virulence of each strain in domestic animals, it is necessary to examine using not only mice but also the concerned animals. We have shown that TgCatJpOk4, a T. gondii strain recently isolated in Okinawa, Japan, has a high virulence against laboratory mice, comparable to highest virulent RH strain in mice; however, the virulence to domestic animals remains unknown. In this study, we examined the virulence using the Microminipig. After infection, four out of five infected pigs showed severe clinical symptoms: inappetence, hypoactivity and tachypnea. Eventually, three out of the five infected pigs succumbed before the end of the observation. Among the three dead pigs, histological analysis revealed that interstitial pneumonia and spotty necrosis in the liver indicating that the TgCatJpOk4 strain has a high virulence not only in laboratory mice, but in pigs as well.

Crocin mitigates γ-rays-induced hepatic toxicity in rats.

Crocin (C44H64O24) is an isolated bioactive molecule of saffron extract. It has different pharmacological effects such as antioxidant and anti-inflammatory activities. In the present study, radioprotective property of crocin was investigated in the rat liver. Thirty-two rats were equally divided into four groups: (1) control (normal saline), (2) crocin (200mg/kg), (3) γ-rays (6Gy), and (4) crocin plus γ-rays-treated groups. The liver histopathology, serum transaminases (ALT and AST), alkaline phosphatase (ALP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) have been assessed. The histopathological result of hepatic tissue in group 3 showed hydropic degeneration and this progressed to focal or spotty necrosis through the lobule. Moreover, some sinusoids are distended with blood or with leukocytic infiltrations. Other cases in group 3 showed periportal leukocytic infiltrations and necrosis extended out from the portal tract to involve hepatic lobules with fibrinous necrosis in portal vessels, while the examination of hepatic tissues of group 4 showed reduced deformities, irregular arrangement, congested hepatic vessels, and necrosis in hepatocytes. The results also showed significant decreased level of liver function activities, inflammatory markers, lipid peroxidation, and increased levels of liver antioxidants enzymes in group 4. Crocin showed moderate protective effect against γ-rays-induced liver toxicity. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters. Graphical abstract .

Drug-Induced Autoimmune Hepatitis in a Patient Treated With Minocycline: A Rare Adverse Effect

Minocycline is an oral broad-spectrum tetracycline antibiotic that is used to treat moderate to severe acne vulgaris as well as certain sexually transmitted infections. Minocycline-induced autoimmune hepatitis can be differentiated from “classic” autoimmune hepatitis by the patient's swift recovery after discontinuing the offending drug and no relapse of the condition upon discontinuation of treatment with corticosteroids. A 31-year-old Chinese woman, with past medical history of acne vulgaris, presented to the Emergency Department with nausea, vomiting, and abdominal pain for the last 3-4 days. She had experienced three episodes of non-bloody, non-bilious vomiting. She described a persistent dull aching pain in the right upper quadrant of the abdomen that had been increasing in intensity, particularly over the last two days. She denied any recent change in her diet. She reported that no one in her household had experienced similar symptoms. She denied any additional recent symptoms. Upon medication reconciliation, it was discovered that the patient had been taking minocycline, on her own and not under medical supervision, for the past three months. Initial laboratory testing was remarkable for significantly elevated transaminase levels with aspartate aminotransferase (AST) of 718 U/L (10-35 U/L) and alanine aminotransferase (ALT) of 1138 U/L (10-55 U/L). An autoimmune workup revealed an elevated antinuclear antibody (ANA) titer (1:160) (<1:40), positive anti-smooth muscle antibodies (ASMA), and the finding of hypergammaglobulinemia (3.2 g/dL) (0.7-1.6 g/dL) with elevated levels of serum immunoglobulin G (IgG) (3176 mg/dL) (700-1600 mg/dL). The bilirubin levels decreased steadily from Day 1 of the hospital admission, but the transaminase levels continued to rise despite discontinuation of the minocycline (Figure 2). On Day 7, she was started on treatment with prednisolone. Also, an IR-guided liver biopsy was performed for the purpose of confirming the diagnosis as well as to assess the degree of liver injury (Figure 3). After two days of treatment with prednisolone, the patient's transaminase levels began to decrease steadily (Figure 2). Physicians should be informed about and suspect drug-induced hepatitis for any individual taking minocycline who presents with elevated LFTs. Physicians who prescribe it to treat acne vulgaris should be aware of this potentially severe adverse effect and stop it immediately when suspicion is raised.2316_B Figure 2. Changes in total bilirubin and alanine aminotransferase (ALT) before and after treatment with prednisolone *Prednisolone, at an initial dose of 50 mg/day, was started on Day 7 of the hospital admission.2316_C Figure 3. Figure 3 (A, B, C, D; left to right). Histopathologic images of the patient's drug-induced hepatitis from liver biopsy A) Piecemeal necrosis. There is chronic inflammation in the portal tracts. H&E stain. 100x. B) Again, there is chronic inflammation in the portal tracts with many plasma cells, lymphocytes, and occasional eosinophils. H&E stain. 400x. C) and D) Spotty necrosis. There is mild chronic inflammation in the portal tracts, as well as ballooning degeneration of hepatocytes indicative of hepatocellular injury. H&E stain. 100x and 400x, respectively.2316_A Figure 1. Abdominal ultrasound There is mild hepatomegaly with increased liver echogenicity.

Potential Protective Role of Selenium on Acrylamide-Induced Oxidative Stress in Rats: A Biochemical, Histopathological Study

Acrylamide (ACR) is an essential chemical which is extensively used in many industries and also in laboratories such as treatment of drinking water, waste water and soil, production of paper, and polishes, used as an additive in some cosmetics, used in electrophoresis and in dentistry for preparation of alloys; it is known as possible carcinogenic compound. French fries, commercially common chips and all carbohydrate containing diet are rich in acrylamide. In this study when Acrylamide is taken into the body, we investigated its toxic effect on body organs and investigated the protective role of selenium. Aim: The aim of this work is to detect acrylamide effects on liver and kidney of adult male albino rats and assess the protective role of selenium. Material and methods: Acrylamide was administrated orally at dose of (15 mg/kg body weight) (1/10 LD 50) daily for 8 weeks. Biochemical parameters in serum were studied: aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), total protiens, Albumin, Globulin, urea, creatinine, and uric acid. Liver and kidneys will be examined by light microscope to evaluate histopathological changes. Tissue malondialdehyde (MDA) was done. Results: The results after being statistically analyzed and tabulated revealed that oral Acrylamide adminstration showed a highly significant (P<0.001) elevation in aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), a highly significant (P<0.001) decrease in serum total protiens, albumin, globulin and highly significant (P<0.001) decrease in serum urea, creatinine, and uric acid levels comparing to control group. Light microscope examination of the hepatic tissue in acrylamide treated group showed obvious congestion associated with wide spread marked vacuolar degeneration as well as foci of spotty necrosis and kidneys showed marked congestion, marked hydropic degeneration of tubular epithelium and focal prominent tubular necrosis. There was a highly significant (P<0.001) increase in malondialdehyde level in acrylamide treated group comparing to control group. Selenium administration in addition to acrylamide showed significant decrease in aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), significant elevation in serum total protiens, albumin, globulin and significant increase in serum urea, creatinine, and uric acid levels comparing to acrylamide treated group. There was significant decrease in malondialdehyde level in acrylamide+sodium selenite treated group comparing to acrylamide treated group

Liver Biopsy Results in Potential Donor Evaluation in Living Related Liver Transplantation

Introduction Living donor liver transplantation has been increasing due to the growing discrepancy between the number of patients in waiting lists for liver transplant and the availability of deceased-donors. The evaluation of potential liver donors should ensure the safety of the surgical procedure for the donor. In addition to this, preoperative tests should identify donor grafts that pose risks for the recipient. Liver biopsy is the gold standard for selecting optimal donors. Our aim in this study is to evaluate the results of preoperative liver biopsy of potential donors. Materials and Methods Between December 1988 and October 2017, we performed 580 LT procedures at our centers (age range, 6 mo – 64 y). We evaluated the demographic features of 612 living related liver donor candidates that we performed liver biopsy between January 2001-June 2017. The histological analyses were examined. Body mass index and gender were compared in predicting the degree of histologically determined steatosis. Results We performed liver biopsy in 612 liver donor candidates (328 male, 284 female) (age range 18-69 years). Among these candidates, 416 liver biopsy were reported as normal (68%); 196 liver biopsies had pathological findings (32%). Of 196 donors with pathological findings; 86 (44%) had fatty changes, 24 (12%) had portal inflammation, 86 (44%) had other pathological findings (like fibrosis, hepatitis, focal spotty necrosis). The mean BMI with steatosis were much more higher than the mean BMI without steatosis (29.7± 3.6 vs 24.8 ± 4.2) ( p<.001). 25% of male and 15% of female donor candidates had steatosis. Conclusion The high rate of pathological findings in liver biopsy of donor candidates with healthy-appearing livers pointed the importance of liver biopsy in preoperative evaluation of donors.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol–induced liver dysfunction: Rescue effect of ginger extract

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent.

Effect of Different Doses of Radiation on Intestinal Injury in NOD/SCID Mice.

Objective To study the effect of different doses of radiation on intestinal injury,with an attempt to find the optimal radiation dose for establishing intestinal injury models in NOD/SCID mice. Methods Forty healthy male SPF-grade NOD/SCID mice were divided randomly into four groups:blank control group and 4-,5-,6-Gy irradiatio groups,with 10 mice in each group. The irradiation rate was 1 Gy/min. The general conditions,body weight,intestinal bacterial translocation,and histopathologic changes were observed and compared. Results The survival rate was 60%,50%,and 30% in the 4-,5-,and 6-Gy groups 15 days after irradiation,and the intestinal bacterial translocation rate was 20%,50%,and 70%,respectively. The body weights in 5-Gy group (P=0.015) and 6-Gy group (P=0.011) were significantly higher than that in blank control group. The length of small intestinal villi decreased in the 4-Gy group. In the 5-Gy group,the structure of intestinal mucosa villi became wide,flat,and inverted,along with the shedding of epithelial cells,the atrophy of glands,and the damage of recess structures. In the 6-Gy group,the structure of intestinal mucosal villi was damaged,the villi were ruptured and smashed,and the recess structures were missing;meanwhile,there was a large amount of inflammatory cell infiltration between tissues,along with visible spotty bleeding and necrosis. The length of small intestine villi in the blank control group and 4-,5-,and 6-Gy groups were (361.77±22.77),(291.68±32.45),(248.03±51.09),and (195.90±26.39) μm,respectively. In particular,it was significantly shorter in 4-Gy group (P=0.005),5-Gy group (P<0.001),and 6-Gy (P<0.001) than in the blank control group,was significantly shorter in the 5-Gy group (P=0.041) and 6-Gy group (P=0.001) than in the 4-Gy group,and significantly shorter in 6-Gy group than in the 5-Gy group (P=0.020). Conclusion 5-Gy irradiation in mice models can decrease body weight,cause the damage of intestinal mucosa and the shedding of inflammatory cells,with stable survival rate and bacterial translocation rate.