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

Heme oxygenase-carbon monoxide system in patients with cirrhosis: relation to splanchnic hemodynamics

Carbon monoxide [CO], an end product of the heme-oxygnase [HO] pathway,is a potent vasodilator and an important modulator of vascular cell function. The present work was designed to study the HO-1/CO system in patients with cirrhosis in relation to severity of liver disease, blood viscosity and splanchnic haemodynamics. Plasma HO-1 levels and blood carboxyhaemoglobin [COHB] concentration,an index of CO production were measured in 30 patients with liver cirrhosis and variable degrees of hepatic dysfunction and in 15 healthy subjects as a controls group. Both patients and control were non smokers. Blood viscosity was measured using the red blood cell pipette viscometer. The blood volume of the portal vein,superior mesenteric artery and splenic artery as well as pusatility index of the arteries were measured using doppler ultrasonography. Plasma [HO-1] levels and blood carboxy haemoglobin concentration were significantly higher in patients with liver cirrhosis than in healthy subjects [p< 0.001]. Also, patients who had esophageal varices, history of bleeding varices, portal hypertensive gastropathy and ascites showed significant increase in HO-1/COHB levels compared with those who did not have these complications [p < 0.001]. The increases in plasma HO-1 level and COHB level showed positive correlation with Child-Pugh score, blood viscosity and the increases in the blood flow volume of the portal vein, superior mesenteric artery and splenic artery and inverse correlation with the decreases in the pulsatility index and the resistive index of the arteries in patients with liver cirrhosis [P< 0.05]. Increased HO-1 activity with enhanced endogenous CO generation may play a role in the development of splanchnic vasodilation and serious manifestations of portal hypertension in liver cirrhosis

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

Breaking the needle diameter limit for radiofrequencythermal ablation for hepatocellular carcinoma. A new technique

A significant number of hepatocellular carcinomas are meet with beyond the ablation field of yet available needles. A new technique had been attempted to increase the field of radiofrequency ablation of expandable electrode needles in the treatment of hepatic neoplasms much larger than the routinely covered size of 5-7 cm according to the needle size overcoming the technical difficulties usually met with in the overlapping balls technique due to the hyperechoic focus that develops at the needle tip making reinsertion difficult and inaccurate. 40 patients were included in the study, all presented with hepatic neoplastic mass lesion that range in size between 7 and 10 cm in its maximum diameter. In this technique, two or three needles were inserted from the start into the mass with accurate estimation of the exact field of ablation of each needle trying to cover the whole extent of the mass before application of radiofrequency waves. All had a pretreatment helical [triphasic] CT study for accurate delineation of the whole extent and vascularity of the mass. Two needles were sufficient to cover the whole extent of the mass in 23 patients [57%] while in the remaining 17 patients [43%] three needles were necessary. The procedure was done under general anathesia and ultrasound guidance, patients tolerated procedure well with smooth recovery. No major complications. Follow up spiral [triphasic] CT was done 2 weeks after ablation revealed percentage of tumour necrosis of 90% or more in 30 patients [75%], 70-90% in 6 patients [15%] while in the remaining four patients [10%] the percentage was 50-70% necrosis. In conclusion this technique should be considered in the treatment of hepatic masses larger than the usual field of the needle

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

Transfer factor activation of the natural killer cell in patients with chronic hepatitis C infection

Infection with hepatitis C virus [HCV] is a leading cause of chronic liver disease worldwide, little is known about how this virus is able to persist or whether this persistance might be because of its ability to alter the early innate immune response. The major HCV envelope protein E2 has been shown to bind to CD81; this leads to restricted cytotoxicity mediated by NK cells. Transfer factor advanced formula plus is formed of bovine and egg colostrum and has been found to increase NK cell activity by 437% above the base line. It is produced by 4 life research company/USA. Also, it contains several growth factors as insulin growth factors [IGF I], [IGF II], Transforming growth factor beta [TGF-B] and epidermal growth factor [EGF]. Assessment of Natural Killer [NK] cell activation by transfer factor in patients with chronic HCV infection whom are not candidate for standard therapy. 30 patients with chronic HCV infection, who are not candidate for standard therapy were subjected to: [1] History and clinical examination. [2] Liver function tests. [3] Viral markers [HBS Ag, HCV Ab]. [4] HCV RNA by PCR in the serum. [5] Flow cytometric analysis of NK cells in blood sample. [6] Patients were given transfer factor plus capsules twice daily before meals for 3 months then re-evaluation was done. Significant reduction of Mean alanine aminotransferase [SGPT] from 79.27 +/- 71.47 to 30.35 +/- 6.21, aspartate aminotransferase [SGOT] from 80.73 +/- 46.88 to 36.40 +/- 3.23 and serum Bilirubin from 1.58 +/- 0.72 to 0.86 +/- 0.33. Significant elevation of serum albumin from 3.19 +/- 0.70 to 3.59 +/- 0.54 and prothormbin activity from 0.63 +/- 0.14 to 0.82 +/- 0.12. No significant change in serum HCV RNA by PCR nor NK cell count by flow cytometry. Transfer factor advanced formula plus is an effective new therapeutic option for patients with chronic HCV infection who are not candidate for standard therapy

Evaluation of zinc status as a liver function test in patients with schistosomal hepatic fibrosis

The association between schistosomiasis and Zinc [Zn] deficiency had been attributed to many causes including malabsorption, hepatic malfunction or reduction in its binding proteins [albumin and a[2] rnacroglobulins]. The present work aimed at the study of the relation between zinc status and the functional reserve capacity of the liver in patients with schistosomal hepatic fibrosis. For this purpose the study included 60 subjects; 15 healthy persons as a control group and 45 patients with schistosomal hepatic fibrosis divided into three equal groups [A, B and C] according to the severity of their liver affection using modified child's classification. It was found that zinc levels in plasma, polymorphonuclear leukocytes and erythrocytes are significantly low in all Schistosomal patients as compared to the control group and usually the more severe the dysfunction is, the more the Zn deficiency. This indicates Zn depletion in both extra and intracellular compartments can be mainly explained by the defective synthesis of plasma proteins by the liver, mainly albumin and a2 macroglobulins that act as carriers of Plasma Zn. However, the hyperzincuria found in these patients may share in the chronic Zn deficiency and it is mostly due to increased diffusible fraction of Zn as a result of hypoalbuminemia