Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients?

Hepatocellular carcinoma [HCC] is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body [90%] is synthesized by enterochromaffin cells of the gastrointestinal tract and is exported to various sites. Serotonin regulates blood flow and vascular tone at portal and sinusoidal levels, serotonin acts as a mitogen for hepatocytes and promotes liver regeneration. 5HT emerges as a mediator of different pathological conditions [double edged sword]. It contributes to liver fibrosis, mediates oxidative stress in nonalcoholic steatotic hepatitis and aggravates viral hepatitis, these conditions are involved in tumourigenesis of hepatocellular carcinoma [HCC]. Impaired metabolic function in liver cirrhosis and slow uptake and storage of serotonin by the platelets is a sequelae of kinetic change of serotonin transport mechanisms or abnormal serotonin release from dense granules of activated platelets is a condition defined as ''platelet exhaustion'', contributes to elevated plasma serotonin which may facilitate tumour growth of primary liver hepatocellular carcinoma. To determine whether serotonin is a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients. Patients were classified into two groups; 45 patients with cirrhosis only and 30 patients with cirrhosis and HCC. Ten healthy subjects were taken as controls. Patients underwent; full history taking, clinical examination, and abdominal ultrasonography. Laboratory methods include SGOT, SGPT, GGT, bilirubin, alkaline phosphatase, total proteins, albumin, CBC, prothrombin, INR, APRI score, Child-pugh score, MELD score, AFP and serum serotonin. Plasma serotonin was significantly higher in the patients group with cirrhosis with a median level of 119.4 ng/ml than in the control group which showed a median value of 51.5 ng/ml p< 0.001. A significance difference was also seen between cirrhosis and the HCC group with a median value of 478.35 ng/ml than the control group and a cirrhosis group with p< 0.001was found. Plasma serotonin level was significantly higher in patients with cirrhosis and HCC than in those with cirrhosis only and it was involved in the tumourigenesis of hepatocellular carcinoma

Adiponectin: a differential marker between steatosis and steatohepatitis

Nonalcoholic fatty liver disease [NAFLD] becoming a world-wide public health problem.It represents a spectrum of disease ranging from simple steatosis to steatohepatitis [NASH]. Adipocytokines refer to adipocyte-derived biologically active molecules TNF-alpha, leptin and adiponectin, all been implicated in development of hepatic inflammation and fibrosis in NAFLD patients. This new hormone differ from its predecssors in important feature, production and concentration actually decrease in obesity, and all adipose-derived hormone are increased. It is possible that adiponectin expression is activated during adipogenesis, a feed back inhibition on its production may occur during the development of obesity. Adiponectin may exert a hepatic protective effect. Was to evaluate adiponectin level as a differential marker between steatosis and Steatohepatitis. Twenty NAFLD patients, twenty biopsy proved NASH and twenty control subjects, matched for age, sex and BMI. All the subjects were subjected to an abdominal ultrasonography, routine biochemical evaluation: liver function ALT and AST, lipid profile [cholesterol, triglycerides, HDL-C], CRP and Adipocytokines [TNF-alpha, IL-6, LEPTIN, and Adiponectin]. Plasma adiponectin levels were significantly lower in NAFLD patients than control gp [6.15 +/- 1.39ng/ml vs12.03 +/- 3.46ng/ml]. Adiponctin was significantly lower in NASH than NAFLD [1.80 0 +/- 0.96 ng/ml vs 6.15 +/- 1.39 ng/ml]. leptin level was significantly higher in NAFLD than NASHgp [69.50 +/- 18.70ng/ml vs 43.20 +/- 6.93ng/ml]. adiponectin ROC curve showed an AUROC curve in NAFLD gp [o.945 p=0.049] while inNASH was[0.995 p=0.007].TNF-alpha and IL-6 was significantly higher in NASH than NAFLD gp [79.25 +/- 13.89 pg/ml vs41.25 +/- 17.53 pg/ml]and [110.20 +/- 55.34 pg/ml vs 43.85 +/- 16.13]. Plasma adiponectin level in NAFLD gp was inversely correlated with T.G [r=-0.368 p=0.111]. GOT [r=-0.037 p=0.878] and GPT [r=-0.022 p=0.926] while it was +ve correlated in NASH gp with Cholesterol [r=0.317 p=0.174] and T.G [r=0.042 p=0.861]. This data support a role for low circulating adiponectin in the pathogenisis of NAFLD and hypoadiponectinemia found to be a feature of NASH. ADIPONECTIN found to be a non-invasive differential marker between NAFLD and NASH

Fibro-acti test, forn's score, APRI score versus liver biopsy in chronic HCV patients

Chronic infection with hepatitis C virus remain a major health problem worldwide. Clinical management of compensated chronic hepatitis C is largely based on assessment of the degree of liver fibrosis. Liver biopsy although is a gold standard for fibrosis staging is an invasive technique. Evaluating a panel of non-invasive markers of liver fibrosis as Fibro-Acti test, APRI score, Forn's score versus liver biopsy. 20 HCV patients were subjected to APRI score, Forn's score, Fibrosure test, and ultrasound guided liver biopsy, with pathological assement using METAVIR score. APRI correlates significantly to the increase in fibrosis stages with correlation coefficient of 0.716 [p = 0.000], also correlates significantly with PCR with correlation coefficient of 0.616 [p = 0.004] and with necroinflammatory changes. Forn's score showed significant correlation with fibrosis stage of 0.416 [p=0.041] and with hepatic pathology for hepatitis activity of 0.725 [p=0.000]. In the present study FT-AT was found to have a greater diagnostic performance than APRI and Forn's score. FT-AT is the only test in which results are reported for prognostic and treatment planning purposes to wave liver biopsy

Glypican 3 amino terminal marker for early detection of hepatocellular cacinoma

HCC is the 5[th] common cancer worldwide. Due to global increase of hepatitis B and C infection, the incidence of hepatocellular carcinoma [HCC] has been steadily increasing. The seroprevalence of HCV in Egypt is currently between 20 -35%. Because Alfa Feto protein [AFP] has limited sensitivity for small hepatocellular carcinoma foci, Glypican-3 [GPC-3] oncofetal protein which is over expressed in HCC could represent a hope for early detection. Evaluating the validity of Glypican-3 as an early detector of HCC. 10 healthy controls and 40 HCV positive patients distributed as follows: 10 patients with chronic hepatitis C virus infection [CH], 10 patients with compensated cirrhosis [CC], 10 patients with decompensated cirrhosis [DC] and 10 patients with HCC. Liver functions: ALT, AST, Bilirubin [T], Albumin, gamma GT. Tumor markers: AFP and GPC-3.Viral markers: HCV antibodies, HBs Ag and HBc Ab. AFP mean was126 ng/ml and GPC-3 mean was 34.63 ng/ml in HCC group which were significantly higher than the other studied groups. No significant correlation was found between AFP and GPC-3.The area under ROC of GPC-3 was higher than AFP suggesting increased GPC-3 sensitivity. AFP showed sensitivity of 70% in HCC, 30% in D.C and 20% in C.C with 100% PPV, also AFP had 100% specificity with low NPV compared to GPC-3. GPC-3 was detected in all HCC groups, DC and CH showing 100% diagnostic performance. GPC-3 in C.C revealed 70% sensitivity with 100% PPV and 100% specificity with low NPV. GPC-3 was elevated in context of patients with CH, CC and DC as it is an oncofetal protein produced by regenerating liver cells. GPC-3 and AFP improve the prediction accuracy of HCC in those seronegative to AFP