Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is now regarded as one of the major malignant diseases worldwide, with significant variations in its epidemiology. OBJECTIVE: study of the epidemiology of hepatocellular carcinoma and its relation to age, sex, residence, and viral hepatitis in Egypt. METHODOLOGY: From January 1992 to May 2005, 1012 cases with hepatocellular carcinoma were diagnosed in the Gastroenterology Center, Mansoura University, Egypt. All patients were evaluated for age, sex, residence, occupation, history of other medical disease, anti-bilharzial treatment, blood transfusion, viral markers, and liver functions. RESULTS: The mean age was 54.26 +/- 9.2, with high prevalence between 51 and 60 years. Male to female ratio was 5:1, farmers constituted 37.6%, workers 22.9% and housewives 12.8% of the patients. The number of HCC patients increases yearly from only 9 patients evaluated at 1992 to 80 patients in the first 5 months of the year 2005. The mean age increased from 45 years at 1992 up to 58 years at year 1996. Seventy-seven percent of the patients were resident in rural areas versus 23% in urban areas. Seventy-eight percent of patients presented with abdominal pain, 7.1% with abdominal swelling, 4.3% with jaundice, 2.4% with other symptoms and 8.8% of the HCCs were discovered accidentally. The prevalence of diabetes mellitus among HCC patients was 13.6%, history of anti-bilharzial treatment was positive in 37.6%. Hepatitis C, B and mixed B&C was 76.6%, 3.3%, 3.6% respectively. History of blood transfusion was encountered in only 10.6%. Twenty-seven percent of HCC patients had previous history of surgery. Clinical and laboratory studies revealed that, 52.1% of patients were Child's A, 37.3% B and 10.7% C. Tumor size >5 cm in 65.5%, the right lobe was the site in 63.9%, left lobe in 25.8% and both lobes in 10.3% of the patients. Lesions were single in 71.1%, multiple in 24.9% and diffuse in 4% of cases. Portal vein thrombosis was detected in 15.9%. Hepatic resection was done in 25.8%, chemoembolizations in 17.2%, radiofrequency in 13.1%, alcohol injection in 0.9%, mixed treatment in 3.5% of patients while 38.7% were managed by conservative treatment due to no available safe treatment. CONCLUSIONS: The number of newly diagnosed patients with HCC increases annually. The prevalence of HCC is high in Nile Delta area, and is more common in males, rural residents and farmers especially in HCV patients. In rural areas there are other risk factors that may be responsible for this high incidence, such as pollution, aflatoxins and use of insecticides, which need more study.

Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma.

Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals (81 patients with liver disease and 42 healthy volunteers). The liver diseases included periportal fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T-cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease ( P<0.01) in CD3 and CD4 T-cells, and a highly significant increase ( P<0.001) in CD57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of liver cirrhosis and HCC.

DNA ploidy of liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma: a flow cytometric analysis.

Flow cytometric DNA analysis was used to assess cellular kinetics of needle liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma (HCC). An abnormal DNA content was shown in 44.5% of liver cirrhosis cases and in 78.6% of tumor sites. The number of proliferating cells (S + G2M%) was significantly increased in cirrhotic liver (P < 0.05). Dysplasia was found in 66% of cirrhotic specimens. All negative dysplasia specimens showed a diploid pattern while 69% of positive dysplastic specimens were aneuploid (P < 0.001). In conclusion, cell proliferation, aneuploidy and liver cell dysplasia are important indicators in liver cirrhosis for the development of HCC.

High prevalence of hepatitis B viral DNA in cirrhotic patients without surface antigen.

The diagnosis of liver diseases induced by hepatitis B virus (HBV) is supported by the detection of HBV surface antigen (HBsAg) in serum. The present study aimed to investigate the presence of HBV deoxyribonucleic acid (DNA) in patients with liver cirrhosis using a polymerase chain reaction (PCR) based on primers derived from the pre-S1 and pre-core regions. HBsAg was detected in 10 of 48 patients (21%), total anti-hepatitis B core antigen (HBc) antibodies in 54%, anti-hepatitis B e antigen (HBeAg) in 14.6%, anti-HBc immunoglobulin M in 8%, and anti-HBs in 26%; none had detectable HBeAg. HBV DNA was detected in 73% of the cirrhotic patients. All cirrhotic patients with HBsAg also had HBV DNA; HBV DNA was detected in 64.5% of those without HBsAg. We conclude that the clearance of HBsAg does not necessarily indicate termination of viraemia in patients with liver cirrhosis and the detection of HBV DNA using a PCR based on primers from the pre-S1 and pre-core regions should be included in the diagnosis of HBV infection.