Incidence Of Hepatocarcinoma Research Articles

Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short- and long-term IFN-free antiviral treatment

Background: New direct-acting antiviral drugs can eradicate hepatitis C virus (HCV) infection in over 90% of patients and can even reduce the risk of complications in advanced fibrosis/cirrhosis. The aims of this study were to evaluate (1) changes in fibrosis during and after antiviral treatment and (2) incidence of hepatocarcinoma and mortality in various fibrosis stages.Methods: This is a longitudinal monocentric prospective study. Blood and instrumental examinations were evaluated at baseline, at the end of therapy, and 1 and 2 years following treatment.Results: Two hundred and ninety-six patients with chronic HCV were evaluated, of whom 115 were experienced, 181 were treatment-naïve, and 2 had previous hepatocellular carcinoma (HCC) and were therefore excluded from the study. At baseline, stiffness values were 13.46 ± 9.97 kPa. Out of the 294 HCV patients enrolled, 100 had lymphoproliferative disorders and were evaluated separately. This group of patients showed stiffness values pertaining to the F0–F2 group (mean stiffness values were 6.07 ± 1.68 kPa). All other patients showed stiffness values pertaining to the F3–F4 group (mean stiffness values were 17.93 ± 10.23). No statistically significant difference was found between stiffness at baseline compared to the end of treatment (EOT), while significant differences were found between the baseline, 1 year (p = .05), and 2 year follow-ups (p < .01). Significant differences were found between baseline and EOT, as well as 1 and 2 years after the end of treatment (p < .001) in the F3–F4 group. Four out of 140 patients with baseline cirrhosis developed HCC during the post-treatment follow-up, 1 of whom died.Conclusions: Non-invasive methods provide important prognostic information, particularly concerning the observed regression of fibrosis and could be extremely useful for monitoring patients with long life expectancies after direct-acting antiviral treatment.

The research progress on comprehensive treatment of primary liver cancer in the elderly

Primary hepatocellular carcinoma (PHC) is a common malignant tumor in our country, which seriously threatens people's health. As China gradually enters the aging society, the elderly over 60 years old take up for 13% of the total population. The incidence of PHC in the elderly is increasing at the same time. At present, the incidence of hepatocarcinoma in China is the third highest among malignant tumors, and 47.5% of the patietns are elderly patients. As the elderly patients are often accompanied by cardiovascular and cerebrovascular diseases, diabetes and other complications, making the treatment of PHC in the elderly become much more difficult. Therefore, adopting a comprehensive treatment model of multiple therapies to improve the quality of life of patients and prolong the survival time of patients, has become the key issue. This article reviews the current progress in the clinical treatment of PHC in the elderly. Key words: Elderly; Primary liver cancer; Multidisciplinary treatment

Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?

It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.

Impacto del tratamiento antiviral en la historia natural del virus de la hepatitis C

Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitisC with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitisC virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitisC virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease.

Vitamin A and All-trans and 9-cis Retinoic Acids Inhibit Cell Proliferation During the Progression Phase of Hepatocarcinogenesis in Wistar Rats

The effects of vitamin A and all-trans and 9-cis retinoic acids on the progression phase of hepatocarcinogenesis were evaluated in this study. For this purpose, male Wistar rats were first submitted to the resistant hepatocyte model of carcinogenesis (diethylnitrosamine for initiation and 2-acetylaminofluorene for selection/promotion). Ten months after initiation, the animals were distributed into four groups and treated by gavage, every other day and during eight weeks, with corn oil (control group), vitamin A (10 mg/kg of body wt), all-trans retinoic acid (10 mg/kg body wt), or 9-cis retinoic acid (10 mg/kg body wt). After this period, the animals were killed one hour after intraperitoneal administration of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg body wt). At the time of sacrifice, liver samples were collected for histopathological (hematoxylin-eosin) examination and immunohistochemical detection of glutathione S-transferase and BrdU, as well as for analysis of retinol and retinoic acid concentrations. Histopathological examination showed the lowest incidence of hepatocarcinomas in vitamin A-treated animals. Moreover, groups treated with retinoids demonstrated lower hepatic BrdU labeling indexes in the neoplastic lesions, as well as in their respective surrounding tissues, than controls. Thus vitamin A and all-trans and 9-cis retinoic acid strongly inhibited cell proliferation when administered during the progression phase of hepatocarcinogenesis. Therefore, the anticarcinogenic effects that have been attributed to these retinoids could be partially related to their capacity of inhibiting in vivo cell proliferation.

Intravenous albumin infusion prevents renal impairment (RI) and improves hospital survival in patients with spontaneous bacterial peritonitis (SBP)

INTRAVENOUS ALBUMIN INFUSION PREVENTS RENAL IMPAIRMENT (RI) AND IMPROVES HOSPITAL SURVIVAL IN PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS (SBP). P.Sort*. M. Navasa* and Soanish aroup for the studv of bacterial infections in cirrhosis. *Hosoital Clinic i Provincial. Barcelona. Soain. One third of patients with SBP develop RI in relation with a deterioration of circulatory function, as reflected by an increase in plasma renin activity (PRA). The development of RI is the most important predictor of hospital mortality in SBP. This study assesses whether plasma volume expansion prevents the impairment in circulatory and renal function and improves hospital survival in these patients. 119 patients with SBP were randomized to receive albumin infusion (1.5 g/Kg body wt. on the 1’ day and 1 g/Kg of body wt. on the 3rd day) plus cefotaxime (n=59) or cefotaxime alone (n=60). At diagnosis, hepatic and renal function, PRA and incidence of hepatocarcinoma were similar in both groups. The incidence of circulatory dysfunction (increase of 50% in PRA above baseline levels at the sixth day of inclusion) (4% vs 30%, p<O.OOl) and of RI (8.5% vs 35%, p<O.OOl), and the hospital mortality rate (10% vs 33%, p<O.O02) were significantly lower in patients who received albumin. Among 31 variables obtained at inclusion, treatment modality, prothrombin time, bilirubin and BUN were the only independent predictors of hospital survival. In conclusion, albumin infusion prevents the deterioration in circulatory function and RI, and reduces hospital mortality in patients with SBP. EVIDENCE OF REDUCED EFFECTIVENESS OF AN OTHERWISE INCREASED ENDGGENOUS DGPAMINERGIC ACTMTY IN COMPENSATED CIRRHOSIS. G Sansot?. A Fenwi. E. Liamldi*. CN Castellana**, G Termnova, M Ghidoni. E Villa, F Manenti. Chairs of Gastmenterologv, ‘Endocrinology and **Clinical Pharmacolqy, Universi@ of Modena, Imly. Endogenous dopamine exerts a combined adrenal and renal mediation of the natriuretic response to central fluid volume expansion. Plasma dopamine levels rise in association with the natriuretic response to volume expansion produced by head-out water immersion. Aldosterone secretion both in rat and in man is inhibited by dopamine. Dopamine inhibits Na’-K’ATPase activity in proximal convoluted and straight tubule segments. In this manner dopamine increases sodium delivery to the distal nephron and natriuresis. We studied 12 patients with Child-Pugh class A cirrhosis without history of previous ascites or diuretic consumption (after an equilibration period of five days on a normocaloric diet with a daily sodium intake of 120 mEq) and compared them to 9 control subjects, on the basis of the evaluation of a) the degree of dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min min atler metoclopramide (h4TC) 10 mg i.v. administration; b) basal morning levels of active renin and aldosterone while reclining ; c) 4 h renal clearances of lithium (C-Li) (an index of fluid and sodium delivery to the distal tubule) and creatinine (C-Cr), d) 4 h urinary excretion parameters of sodium and potassium. With respect to controls, patients showed signiticantly greater incremental aldosterone responses both 30 and 60 min atler MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, ~4.01; +60 min: 140.5 f 80.3 v 36.8 i 39.0 pg/ml, p<o.Ol). hi spite of this, patients and controls showed not significantly different values of basal morning aldosterone (respectively, 80.36 f 53.22 v. 111.70 f 54.56, p=O.14), distal delivery of sodium (respectively, 4.25 * 1.30 v. 3.97 f 1.64 mEq/min, H.13) and urinary excretion of sodium (respectively, 0.14 f 0.08 v. 0.20 f 0.05 mEq/min, ~4.76). Remarkably, we observed a significant correlation between basal aldosterone plasma values and the aldosterone response 30’ after MTC among cirrhotic patients (r: 0.81, p<o.Ol) but not controls (r: 0.07, e.05). These data suggest, in patients with compensated cirrhosis, a state of partial resistance to the renal and adrenal effects of dopaminergic activity which is actually increased with respect to normal subjects. The known dependence of dopaminergic function on the degree of central fluid volume replenishment and the correlation observed only in patients between this parameter and a main determinan t of central fluid volume (i.e. plasma aldosterone levels) could imply the concept of a state of central hypervolaemia in compensated cirrhosis.

A review of the hepatic tumors related to mixed-function oxidase induction in the mouse.

Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and sustained centrilobular hypertrophy associated with a hyperplastic response. In many studies, the long-term sequela of prolonged exposure is an increased incidence of lesions considered to be adenomas. Studies have shown in aged control mice that the burden of adenomas usually consists of lesions with basophilic cytoplasic staining and a uniform population of hepatocyte nuclei. With long-term feeding of MFO inducers, there is an additional burden of lesions diagnosed as adenomas having a different histological appearance with increased eosinophilic cytoplasm and pleomorphic nuclei. The incidence of hepatocarcinomas usually is not modified by the increased incidence of eosinophilic adenomas. Studies into the behavior of the eosinophilic lesions show that the hepatocytes approximate in their behavior to normal and not neoplastic cells. It is suggested that these lesions should not be considered a carcinogenic response to the chemical.

Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice.

A precise targeting of the SV40 T early region expression in the liver of transgenic mice was obtained using 700 bp of the antithrombin III regulatory sequences to control oncogene expression. In the strain expressing the highest level of large T antigen (Tag), the incidence of hepatocarcinoma was 100%. The evolution was reproducible and characterized by a marked cytolysis occurring as early as 4 weeks, when no morphological and histological modifications were visible, a preneoplastic state marked by a progression from hyperplasia to proliferative nodules composed of highly differentiated cells exhibiting a high Tag expression, which elicited tumor formation in nude mice and could proliferate in vitro, and hepatocellular carcinoma associated, in 10% of the cases, with lung metastasis. These transgenic mice constituted a useful model for therapeutic assays and fundamental studies on carcinogenesis.

The hepatocarcinogenicity of diethylnitrosamine to rainbow trout and its enhancement by Aroclors 1242 and 1254

Rainbow trout ( Salmo gairdneri) were fed diets containing 100 ppm Aroclor 1242 (AC42) or Aroclor 1254 (AC54) in combination with 1100 ppm diethylnitrosamine (DEN) for one year. The incidence of hepatocarcinomas was determined and compared with the incidence in trout fed 1100 ppm DEN alone. The two Aroclors dramatically enhanced tumor incidence from 10.2% in the positive controls (DEN alone) to 40.2% for AC42 and 21.6% for AC54. This is in contrast to previous results obtained when AC54 was fed concomitantly with aflatoxin B 1 (AFB 1), where a substantial inhibition of carcinogenesis was observed. The alteration of chemical carcinogenesis in trout by PCB, therefore, depends upon the carcinogen involved and is not a generalized effect.

Histochemical studies of hepatocellular carcinomas in the rat induced by aflatoxin.

A histochemical study has been done on a group of 18 hepatocarcinomas induced by aflatoxin. One hundred per cent, incidence of hepatocarcinomas is induced by feeding 5 p.p.m. aflatoxin for 6 weeks. The carcinomas were trabecular hepatocarcinomas with a mixed adenomatous pattern and showed considerable variation in histochemical reactions throughout the lesions. There was a patchy distribution of glycogen and glucose-6-phosphate and the membrane ATPase was present along much of the canalicular border of the cells but with an abnormal and tortuous pattern. Aniline hydroxylase was present in varying amounts in both trabecular and adenomatous carcinomas. It is concluded that the histological variants of hepatocarcinoma are all derived from hepatocytes, but no unique changes were observed related to the progress involved in malignant neoplasia. The observations form a basis for comparison with early lesions seen prior to the recognition of carcinoma.

Incidence of hepato-carcinoma in relation to aflatoxin intake.

Incidence of hepato-carcinoma in relation to aflatoxin intake.