Genetic and metabolic aspects of non-alcoholic fatty liver disease (NAFLD) pathogenicity

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease showing a rising prevalence globally. Genetic predisposition plays a key role in the development and progression of the disease pathogenicity. Main body This paper summarizes genetic associations based on their influence on several metabolic aspects such as lipid metabolism, glucose metabolism, hepatic iron accumulation and cholesterol metabolism toward the NAFLD pathogenicity. Furthermore, we present variations in some epigenetic characters and the microRNA profile with regard to NAFLD. Conclusion As reported in many studies, the PNPLA3 rs738409 variant seems to be significantly associated with NAFLD susceptibility. Other gene variants like TM6SF2 rs58542926, MBOAT7 rs641738 and GCKR variants also appear to be more prevalent among NAFLD patients. We believe these genetic variants may provide insights into new trends in developing noninvasive biomarkers and identify their suitability in clinical practice in the future. Graphical abstrac

Synchronous liver metastasis in colorectal cancer in Sri Lanka

Abstract Objective To assess the incidence of synchronous colorectal liver metastasis in patients referred to a tertiary referral center in Sri Lanka and to evaluate the differences in the clinicopathological features of patients with and without synchronous metastasis. Methods Records of 438 patients were retrospectively analyzed. Patients were classified into metastatic group (n=34, 8%) and non metastastatic group (n=404, 92%). In the two groups macroscopic features compared were: tumor size (2 cm, 2-5 cm, and >5 cm), site of primary tumor and side of liver involved. Carcinoembryonic antigen (CEA) levels were recorded. At microscopy, tumor differentiation, invasion and nodal status were evaluated. Results The rectum was the primary site of the tumor in a majority (60%) of patients. There was no difference in the distribution of the primary site and size of the tumor, pathological stage, lymphatic infiltration and the degree of tumor differentiation in two groups (p>0.05). Patients with metastasis had higher levels of CEA, higher frequency of vascular infiltration and N3 nodes involved (p<0.05). Conclusion The incidence of synchronous colorectal liver metastasis seems to be lower in our patients. Association of higher CEA level, advanced nodal stage and presence of vascular invasion needs to be further assessed with risk of developing metachronous liver metastasis. Keywords Colonic neoplasms . Liver neoplasms/surgery Carcinoma of the large bowel is the fourth commonest cancer worldwide Methods Data on 438 patients, who were registered in the University of Kelaniya colorectal cancer database from 1999 to 2009, were analyzed retrospectively. A synchronous metastatic deposit was defined as a liver lesion detected during preoperative work-up (abdominal ultrasound scan and computed tomogram) or at the time of surgery. Patients were classified into two groups based on presence or absence of synchronous liver metastasis. Macroscopic features assessed were: tumor size (2 cm, 2-5 cm, and >5 cm), site of primary tumor and side of liver involved. Carcinoembryonic antigen (CEA) levels were recorded. At microscopy, tumor type, invasion and nodal status were evaluated Statistical analysis was done by comparison of proportions using Chi square list. A p value <0.05 was considered significant. Results The 438 patients (51.8%, n=227) had a mean age of 58 (SD 14.5) years. Of these, 405 patients underwent colonic resection, and 23 underwent colostomy for decompression

Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral aetiology – a prospective study

Abstract Background 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. Methods Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011–2015 were screened. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated against patient characteristics, tumour characteristics and survival. Results Three hundred eighty-nine patients with nvHCC [age 64(12–88) years; 344(88.4%) males] were screened. Median AFP was 25.46 ng/ml (1.16–100,000). 41.2% (n = 160) Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05), late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels. Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was associated with longer survival (16 vs. 7 months, P < 0.001). Conclusion Pre treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over 400 ng/ml was associated with aggressive tumour behaviour and poor prognosis