New Liver Biopsy Research

Research -1

Can We Use Osteopontin as a Reliable Marker for Diagnosis of Early HCC in Chronic HBV Monoinfected Saudi Patients

Background: Chronic hepatitis is a worldwide disease with a catastrophing end as hepatocellular carcinoma (HCC). The objective of the current study was to assess performance of biomarkers for early detection of HCC among Chronic Monoinfected HBV Saudi patients. We selected alpha feto protein (AFP) and serum Osteopontin (OPN) as biomarkers to investigate their performance as early diagnostic biomarkers. Subjects and methods: 250 Saudi subjects were included in this study and classified into three groups. First group included 50 healthy subjects serving as control group. Second group consisted of 100 patients suffering from liver cirrhosis. The third group included 100 patients suffering from Early HCC. The condition of liver pathology (in early HCC patients) was confirmed by liver biopsy or spiral CT scan. Demographic and biochemical investigations were recorded and both alpha-feto protein (AFP) and osteopontin (OPN) were measured. Results: Performance of markers included in diagnosis of early HCC AUC was 0.78 for AFP and 0.87 for osteopontin; the best cutoff value for AFP was ≥25 ng/ml; while for OPN it was ≥135 ng/m. At the best cutoff value OPN had sensitivity of 100%, specificity 65%, PPV 66.7% , NPV 84.6% and overall accuracy 93% (CI: 0.621-0.931 and P value: 0.003), AFP showed 90% sensitivity, 55% specificity, PPV 74%, NPV 89% and overall accuracy 80% (CI: 0.765-0.980 and P value: 0.001).

Conclusion: OPN showed better sensitivity in diagnosis of early HCC than AFP and plasma OPN estimation can be considered as a reliable marker for diagnosis of early HCC.

Research -2

A Case of Sarcoidosis Presenting as Cirrhosis and Portal Hypertension

Sarcoidosis is a systemic granulomatous disease of unknown etiology that can involve nearly all organs. Liver is the third most commonly affected organ following the lungs and the lymph nodes. Cases with liver sarcoidosis are usually silent clinically while a few can progress to cirrhosis and portal hypertension in less than 1% of the patients. A 56 year old female was referred for ecchymosis, protuberant abdomen, bilateral pretibial and ankle edema. Medical history did not reveal any previous disease. Ascites, hepatomegaly, splenomegaly, and facial telengiectasies were present on physical examination. Chest x-ray and CT were normal. Papules and plaques on the knees developed six days after admission. Skin biopsy revealed granulomatous dermatitis. Serum ACE was 250IU/L. Liver biopsy showed non-caseiting granulomas, severe hepatitis and fibrosis. Sarcoidosis was confirmed based on high serum ACE, histopathologic findings of the skin and liver biopsy samples that revealed non-caseiting granulomas. We report a case of sarcoidosis complicated by cirrhosis as the initial manifestation of the disease without lung involvement. An extensive literature review of sarcoidosis, focusing on case reports, which presented with cirrhosis and portal hypertension without lung involvement, was made.

Research -3

Grifola frondosa Extract Induced Acute Hepatic Injury

Aim: To describe a case of acute hepatic injury related to the use of Grifola frondosa in a patient with colon cancer. Case Presentation: Patient is a 67 year old female with stage IV poorly differentiated adenocarcinoma of the colon, who presented with epigastric pain one month after resection of her primary tumor. A staging PET scan revealed metastasis to regional lymph nodes without solid organ involvement. Her home medications include longstanding amlodipine and losartan, and a recently started Grifola frondosa derivative. Her laboratory data was significant only for acute transaminitis (AST:967 U/L, ALT:768 U/L) without hyperbilirubinemia. Alcohol, acetaminophen, and a viral panel (EBV, CMV, hepatitis A/B/C) were all negative. A CT scan revealed heterogenous liver parenchyma without focal lesions. A subsequent liver biopsy demonstrated active portal inflammation with eosinophilic infiltration. Discussion: The etiologies of significant acute transaminitis include viral hepatitis, ischemic liver injury, acetaminophen toxicity and drug-induced liver injury (DILI). Viral and ischemic hepatitis and acetaminophen toxicity were excluded based on laboratory analysis and imaging studies. Liver biopsy findings demonstrating the characteristic eosinophilic infiltration of a drug reaction favored DILI as the etiology of transaminitis in this case. With a RUCAM score of 7 calculated based on history, clinical course, and objective data, DILI was concluded to be probably attributed to the patient’s recent use of the Grifola frondosa extract. Conclusion: A diagnosis of drug induced liver injury probably secondary to the use of Grifola frondosa extract was made after excluding all other causes of significant acute transaminitis.

Research -4

Hypoxia Inducible Factor 1α as a Diagnostic and Predictor Test of Liver Fibrosis

Introduction: Regulation of the the metabolic activities of the liver is done by oxygen, which is considered as a critical signaling molecule in that issue. Oxygen delivery dysregulation provoke hepatic steatosis and inflammation. Hypoxia inducible factors (HIF1α) control the expression of gene essential for adaptation to low level of oxygen. In the state of cell hypoxia, (HIF 1α) protein level increase.

Aim of the Work: Study the role of hypoxia inducible factor (HIF1α) as non-invasive marker and predictor of cirrhosis.

Patients and Methods: The study was conducted on 80 patients selected from chronic hepatitis c patients at National Liver Institute, Menofia university. Subjects were randomized into 2 main groups according to the degree of liver disease: Non-Cirrhotic group; included 40 cases with early fibrosis; while Cirrhotic group included 40 cases with liver cirrhosis; and finally, Control group: included 20 apparently healthy with no definite fibrosis by liver biopsy(historical control). Excusion criteria included, Hepatic tumors, or hepatic focal lesion, Vascular liver diseases or, portal, superior mesenteric, thrombosis, and unfit for US guided liver biopsy, all subjects had liver function tests, virology screen, complete blood counts, serum creatinine, fasting and two hours postprandial blood sugar, abdominal ultrasound, recent liver biopsy and hypoxia inducible factor (HIF1α) assay.

Results: Non-Cirrhotic group showed moderate significant positive correlation between grade of fibrosis and HIF1α level, while there was inverse, moderate, significant correlation between albumin and HIF1α. Cirrhotic group, showed significant positive correlation between HIF1α, and total bilirubin, direct bilirubin, PT and INR while there was significant negative correlation with albumin. HIF1α was significantly increased with increased fibrosis grade. HIF1α level significant increased in Cirrhotic group compared to Non-Cirrhotic (2.16±0.65 vs 1.02±0.41 respectively), and in decompensated cases compared to compensated cases (2.50±0.46 vs 1.72±0.60 respectively). Finally, HIF1α had a predictor values for diagnosis of early fibrosis as area under the curve (AUC) was 0.97. The best cut off value was 0.68, with 92.5% sensitivity and 90.0% specificity.

Conclusion: HIF1α can be a useful sensitive, diagnostic, and predictor marker of hepatic fibrosis.