Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Association of serum ferritin with diabetes and alcohol in patients with non-viral liver disease-related hepatocellular carcinoma(S. Karger, 2017) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; Ediriweera, D.; Gunetilleke, B.; Sivasundaram, T.; de Silva, H.J.INTRODUCTION: Non-alcoholic fatty liver disease is a leading cause for hepatocellular carcinoma (HCC) in Sri Lanka. Diabetes mellitus, alcohol abuse, and liver inflammation are known to increase the risk of HCC. The present study evaluates serum ferritin levels in a cohort of patients with non-viral HCC (nvHCC). METHODOLOGY: Consecutive patients with nvHCC presenting to the Colombo North Liver transplant Service, Ragama, from January 2012 to July 2013 were investigated. All were negative for hepatitis B and C. At registration, 5 mL of serum was separated into plain tubes, stored at -80°C and analysed for ferritin using an enzyme-linked immunosorbent assay. Correlation between the serum ferritin and patient risk factors, liver status, and tumour characteristics were analysed. RESULTS: There were 93 patients with nvHCC (median age 65 [12-82] years; 82 [88.2%] males). The median ferritin level was 246.2 μg/L, and 38 (40.86%) patients had elevated ferritin. Non-diabetics (median 363.5 mg/L, p = 0.003) and alcohol abusers (median 261.2 mg/L, p = 0.018) had higher ferritin levels. On multiple-variable analysis, being non-diabetic (p = 0.013) and alcoholic (p = 0.046) was significantly associated with high serum ferritin. No association was found with body mass index, tumour stage, size, macrovascular invasion, number of nodules, alpha-fetoprotein, bilirubin, international normalized ratio, and survival. CONCLUSION: In patients with nvHCC, serum ferritin levels are higher in non-diabetics and alcoholics.Item Clinical predictors of poor outcomes in hepatocellular carcinoma of nonviral aetiology(Sri Lanka Medical Association, 2017) Siriwardana, H.D.R.C.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; Gunetilleke, B.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Clinical predictors for prognosis of NASH and alcohol related (non-viral) hepatocellular carcinoma (nvHCC) is poorly described. METHODS: Patients with nvHCC, from a tertiary referral hepatobiliary clinic were prospectively screened. Clinical evaluation, liver biochemistry, pre-treatment AFP (pt-AFP) and contrast enhanced CT abdomen were performed. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed in HCC negative for HBsAg, anti-HCVantibody, autoimmune and metabolic screening. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. Cox regression analysis was used to identify the factors associated with mortality. RESULTS: A total of 472 patients with nvHCC [age-64 (12-88) years; males-417 (88.3%)] were screened [261 (61.1%) had diabetes; 212 (48.8%) were regular, 85 (19.6%) social, 137 (31.6%) nonconsumers of alcohol]. 358 (83.4%) had cirrhosis [Child A (58.3%), B (32.8%), C (8.9%); median CTP 6 (1-14), MELD 11 (5-40)]. 170 (42.2%) HCCs were TNM stage 3, with median diameter 6cm (0.9-26.5). 239 (71.6%) had no vascular or visceral invasion. Median pt-AFP was 26.6ng/ml (1.16-100,000) [pt-AFP>200ng/ml: n=90 (31.4%) pt-AFP>400ng/ml: n=68 (23.8%)]. Gender, alcohol use (consumer/not), diabetes (present/absent), cirrhosis (present/absent), Child-class (A or B/C), total diameter (<5cm or ≥5cm), nodularity (single/multiple), vascular invasion (present/absent), TNM stage (early/late) and pt-AFP level (<200 or ≥200ng/ml) were assessed as predictors of mortality. On bivariate analysis, Child B/C class (p<0.05), vascular invasion (p<0.001), TNM stage 3 and 4 (p<0.05) and pt- AFP≥200ng/ml (<0.05) were predictive of death. On multivariate analysis, TNM stage ¾ (p<0.05, HR=2.07 and 4.07 respectively) and pt-AFP level≥200ng/ml (p<0.05, HR=1.71) remained independently predictive of death. CONCLUSION: Among patients with nvHCC, TNM stage 3/4 and pt-AFP≥200ng/ml independently predicts death.Item Significance of pre-treatment serum alpha-fetoprotein in hepatocellular carcinoma of non-viral aetiology(Sri Lanka Medical Association, 2016) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; Gunetilleke, B.; de Silva, H.J.INTRODUCTION: Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear. METHOD: Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011-2015 were screened. Clinical evaluation, liver biochemistry, pt-AFP and contrast enhanced CT abdomen were performed. HCC was diagnosed using American Association for the Study of Liver Disease guidelines and TNM staged. nvHCC was diagnosed in HCC, negative for HBsAg and anti-HCVAb. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. All values are presented as median (range). Differences between groups were tested using Pearson’s Chi-square, Mann Whitney U and Kruskal-Wallis tests. Cumulative survival and recurrence rates were calculated by the Kaplan-Meier method. Difference between survival was evaluated by the log-rank test. A p<0.05 was considered significant. RESULTS: Three hundred and eighty nine patients with nvHCC [age 64 (12-88) years; 344 (88.4%) males] were screened. Two hundred and thirty three (59.9%) had diabetes; 187 (48.1%) were regular, 79 (20.3%) social, 123 (31.6%) non-consumers of alcohol]. Three hundred and twenty nine (84.6%) had cirrhosis [Child A (57.3%), B (32.4%), C (10.3%); median CTP 6 (1-14), MELD 11(5-28)]. One hundred and seventy seven (45.5%) HCCs were TNM stage 3, with median diameter 6cm (0.9-26.5). Two hundred and thirty three (59.9%) had no vascular or visceral invasion. Median AFP was 25.46ng/ml (1.16-100,000) [AFP<10ng/ml: n=160(41.2%), AFP>400ng/ml: n=89(22.9%)]. Females (p<0.05), vascular invasion (p<0.001), diameter>5cm (p<0.05), late TNM stage (p<0.001) and non-surgical candidates had higher AFP levels. Diffuse (p<0.001), invasive (p<0.001) and late stage tumours (p<0.001) had AFP>400ng/ml. AFP<400ng/ml was associated with longer survival compared to AFP>400ng/ml (16 vs. 7 months, p<0.001). CONCLUSIONS: Although pt-AFP was not helpful for diagnosis of nvHCC, AFP>400ng/ml was associated with aggressive tumour behaviour and poor prognosis.Item Clinical characteristics and outcome of hepatocellular carcinoma in alcohol related and cryptogenic cirrhosis:a prospective study(Elsevier, 2015) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; Liyanage, C.; Gunetilleke, B.; Jayathunge, S.; de Silva, H.J.BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease. Hepatocellular carcinoma (HCC) is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC (cryptogenic HCC) behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. METHODS: A total of 150 consecutive patients with HCC (89 cryptogenic HCC and 61 alcohol related HCC) referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. RESULTS: Alcohol related HCC was seen only in males. Compared with cryptogenic HCC, alcohol related HCC had significantly higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (1.7 vs 1.4, P=0.002), model for end-stage liver disease score (13 vs 11, P=0.018) and Child's score (7 vs 6, P=0.037). No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival (5.3 months) compared with cryptogenic HCC (9.3 months, P=0.034). CONCLUSIONS: Compared with cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median survival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.