Carcinoma, Hepatocellular ; pathology ; virology ; Inflammation ; Liver Neoplasms ; pathology ; virology ; Myeloid Differentiation Factor 88

Animals ; Apoptosis ; Carcinoma, Hepatocellular ; pathology ; virology ; Cell Line, Tumor ; Cell Proliferation ; Hepatitis B virus ; Hepatocytes ; pathology ; virology ; Humans ; Liver Neoplasms ; pathology ; virology ; Trans-Activators ; genetics ; metabolism ; physiology

OBJECTIVETo analyze the clinicopathologic characteristics of well-differentiated hepatocellular carcinoma (WD-HCC), and to find clues for its pathologic diagnosis and differential diagnosis.

METHODSSeventy-three cases of WD-HCC were studied with clinical data analysis, gross and microscopic examination.

RESULTSAmong the 73 cases, the prevalence of HBV (+) and/or HCV (+) was 94.5% (69/73), liver cirrhosis was 80.8% (59/73), increased hepatic cell density was 95.9% (70/73), dilated and irregular hepatic sinus was 89.0% (65/73), prominent trabecularism was 89.0% (65/73), increased cytoplasmic eosinophilia or basophilia was 90.4% (66/73), glandular-like structure was 16.4% (12/73, and fatty degeneration was 42.4% (31/73) .

CONCLUSIONSThere are important clinicopathologic features associated with WD-HCC. These features are useful in the differential diagnosis of WD-HCC with dysplastic nodule (DN), focal nodular hyperplasia (FNH) and hepatocellular adenoma.

Adenoma, Liver Cell ; pathology ; Carcinoma, Hepatocellular ; pathology ; virology ; Cell Count ; Diagnosis, Differential ; Focal Nodular Hyperplasia ; pathology ; Hepacivirus ; Hepatitis B virus ; Humans ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; virology

Angiomyolipoma ; pathology ; Bile Duct Neoplasms ; pathology ; virology ; Bile Ducts, Intrahepatic ; Carcinoma, Hepatocellular ; pathology ; virology ; Carcinosarcoma ; pathology ; Cholangiocarcinoma ; pathology ; virology ; Hepatitis B ; Hepatitis C ; Humans ; Liver Neoplasms ; pathology ; virology ; Pathology, Clinical ; trends

Hepatocellular carcinoma (HCC) is one of the most common cancer worldwide. Most of the HCC occur in developing countries. Chronic hepatitis B virus (HBV) infection is an important risk factor for HCC development. HBV induces immune-mediated chronic hepatitis, liver injury, regeneration and scar forming responses, leading to an inflammatory, fibrotic and immune deficient microenvironment. HBV may integrate into host genome, inducing genetic abnormality and altering the expression of HCC-related genes. HBV also expresses active proteins such as X (HBx) and S proteins, which may trans-activate HCC-related proteins expression, interact with intracellular specific proteins, activate a variety of signaling pathways, and induce aberrant epigenetic modifications. HBV mutation also has impact on HBV related HCC development.
Carcinoma, Hepatocellular ; pathology ; virology ; Epigenesis, Genetic ; Hepatitis B virus ; Hepatitis B, Chronic ; pathology ; Humans ; Liver Neoplasms ; pathology ; virology ; Mutation ; Signal Transduction ; Trans-Activators

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; enzymology ; pathology ; virology ; Hepacivirus ; genetics ; Humans ; Liver Neoplasms ; enzymology ; pathology ; virology ; Telomerase ; metabolism ; Viral Core Proteins ; genetics ; metabolism

Carcinoma, Hepatocellular ; pathology ; virology ; Cisplatin ; pharmacology ; Drug Synergism ; Flavonoids ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; virology ; Trans-Activators ; Tumor Cells, Cultured ; Viral Regulatory and Accessory Proteins ; drug effects

Apoptosis Regulatory Proteins ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; virology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; virology ; Newcastle disease virus ; physiology ; Oncolytic Viruses ; physiology ; Tumor Cells, Cultured

OBJECTIVETo investigate the distribution of hepatitis B virus (HBV) genotype in Guizhou and to study the relationship between the genotype and the progression of liver disease.

METHODS786 patients with chronic HBV infection, from 4 cities of Guizhou, including 346 asymptomatic carriers (ASC), 313 chronic hepatitis (CH), 77 liver cirrhosis (LC), 50 hepatocellular carcinoma (HCC) were examined. HBV genotype was determined by restriction fragment length polymorphism analysis and the subtypes were determined by direct sequencing of PCR product in 94 patients with HBV B genotype, the relationship between HBV genotype and the progression of liver disease was studied by multifactor analysis such as HBeAg positivity, HBV DNA load and ALT level.

RESULTSOf the 786 patients, 7 (0.89%), 497 (63.23%), 275 (34.99%), and 7 (0.89%) belonged to genotype A, B, C, D, respectively. There was statistically significant difference in the distribution of genotype B among Kaili (96.04%), Zunyi (78.79%), Duyun (64.52%) and Guiyang (53.14%) (P< 0.01). Genotype C was more prevalent in Guiyang than in other three cities (P < 0.01, or P < 0.05). Out of 94 genotypes B, 93 (98.94%) belonged to subtype Ba, only one was subtype Bj. There were statistically significant difference in the distribution of genotype B and C among various stage of liver disease (P < 0.05 or P < 0.01). Genotype B showed a gradual decrease from ASC, CH, LC to the HCC group while in contrast, genotype C showed a gradual increase in the same order. The ALT levels and the mean age were significantly higher and older in patients with genotype C than those in genotype B (P < 0.01 or 0.05). The HBeAg positivity was significantly lower in genotype C than that in genotype B (P < 0.025).

CONCLUSIONData showed that there were genotype A, B, C and D existing in Guizhou. Genotype B was the major one but genotype C was more commonly seen. In genotype B, subtype Ba appeared to be predominant. The geographic distribution of genotype B and C were different in some cities of Guizhou. Compared to genotype B, genotype C was associated with the development of more severe liver damage.

Carcinoma, Hepatocellular ; pathology ; virology ; DNA, Viral ; analysis ; Disease Progression ; Genotype ; Hepatitis B virus ; classification ; genetics ; Hepatitis B, Chronic ; genetics ; pathology ; Humans ; Liver ; pathology ; Liver Cirrhosis ; pathology ; virology ; Liver Neoplasms ; pathology ; virology ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.
Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Hepatocellular/*etiology ; Hepacivirus/genetics/*pathogenicity ; Hepatitis C/complications/pathology/virology ; Humans ; Liver Neoplasms/*etiology ; Risk