Evolutionary Changes of Hepatitis B Virus Pre-S Mutations Prior to Development of Hepatocellular Carcinoma
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Background and Aims Deletions/mutations in the hepatitis B virus (HBV) pre-S region have been associated with hepatocellular carcinoma (HCC). We aimed to study the evolutionary changes of pre-S mutations prior to HCC development. Methods We studied the HBV pre-S sequences at 1 to 10 years preceding diagnosis of HCC in 74 patients with HBV-related HCC (HCC group). 148 chronic hepatitis B patients matched for sex and age in 2:1 ratio, who had been followed up for at least 3 years without HCC (HCC-free group) were recruited as controls. 56 and 47 patients of HCC and HCC-free groups respectively had serially stored sera for longitudinally examination at 1–3 years, 4–6 years, 7–9 years and ≥10 years prior to the recruitment of the study. Results Compared to the HCC-free group, higher frequencies of pre-S deletions and point mutations (at 11 codons) were observed in the HCC group (p<0.05). Multiple logistic regression analysis showed that pre-S deletions, point mutations at codon 51 and 167 were independent factors associated with HCC. Longitudinal observation showed that pre-S deletions and most of the 11 HCC-associated pre-S point mutations existed at least 10 years before HCC development, and were more prevalent preceding HCC development in patients from HCC groups than HCC-free group. The number of HCC-associated pre-S point mutations increased over time preceding HCC development, and correlated positively with the time to HCC diagnosis (r = 0.220, p = 0.005). Conclusions High prevalence and cumulative evolution of pre-S mutations preceding HCC development suggested a possible carcinogenic role of pre-S mutations and their potential application in HCC risk prediction.Keywords:
Hepatitis B
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This is a cross-sectional study to determine the prevalence and risk factors for transmission of hepatitis B virus (HBV) infection in the Gezira state of central Sudan prior to the introduction of blood screening and vaccination against HBV.The study was carried out on the population of Um Zukra village in Gezira state of Central Sudan. The village was surveyed on five consecutive days in Dec 2000. Epidemiological characteristics were recorded and participants were interviewed for risk factors of viral hepatitis. Blood samples were then collected and tested for HBsAg and HBcAb.A total of 404 subjects were screened with a mean age of 35 years; 54.9% were females, HBsAg and HBcAb were reactive in 6.9% and 47.5% of the studied population, respectively. Exposure to HBV increased with increasing age. The only significant risk factor for transmission of infection was a history of parenteral antischistosomal therapy.This study shows that prevalence of HBV infection is high in the studied population and it is hoped that introduction of blood screening and vaccination against HBV would decrease the carrier pool in the next few years.
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OBJECTIVE To know more clearly about the situation of Hepatitis B virus markers in clinical medical workers and take further interventional strategies to protect high risk medical workers.METHODS Hepatitis B virus markers in doctors,nurses and medical checkers who have contacted with patients′ blood,body fluid,or other occupational hazard situation,were detected by of ELISA.RESULTS Among the 587 medical workers detected,311 were with deficiency of active immunity(52.98%),196 were HBV infectors(33.39%).CONCLUSIONS Medical workers are in high risk groups of HBV infection.Medical institutions should attend to their self-protection and encourage them to take HBV vaccine to prevent iatrogenic transmission.
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Foreword. Preface. 1. The background to hepatocellular carcinoma and the liver. 2. Premalignant lesions of hepatocellular carcinoma. 3. Pathomorphologic characteristics of early-stage small hepatocellular carcinoma. 4. Morphologic evolution of hepatocellular carcinoma: from early to advanced. 5. Angioarchitecture of hepatocellular carcinoma. 6. Advanced hepatocellular carcinoma. 7. Multicentric occurrence of hepatocellular carcinoma. 8. Combined hepatocellular carcinoma and cholangiocarcinoma. 9. Nodular lesions mimicking hepatocellular carcinoma. 10. Biopsy diagnosis of tumorous lesions of the liver. 11. Chemoprevention of hepatocellular carcinoma. Index
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Hepatocellular carcinoma is the most common malignancy among males and the 7th among female patients in the Kingdom of Saudi Arabia. This is due to the endemicity of hepatitis B and hepatitis C. Spontaneous rupture of hepatocellular carcinoma is rare. We report 4 cases of spontaneous rupture of hepatocellular carcinoma. Initial control of bleeding was achieved surgically in 3 patients and by embolization in the 4th patient. All patients had very good hepatic reserve as reflected by Child-Pugh scoring (A & B). We found that the incidence of ruptured hepatocellular carcinoma among 85 patients was 4.7%. The prognosis of this subgroup of patients is poor as reflected by the low median survival ranging from 6-16 weeks.
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Early detection of hepatocellular carcinoma (HCC) is crucial in providing more effective therapies. As routine laboratory variables are readily accessible, this study aimed to develop a simple non-invasive model for predicting hepatocellular cancer.Two groups of patients were recruited: an estimation group (n = 300) and a validation group (n = 625). Each comprised two categories: hepatocellular cancer and liver cirrhosis. Logistic regression analyses and receiver operating characteristic (ROC) curves were used to develop and validate the HCC-Mark model comprising AFP, high-sensitivity C-reactive protein, albumin and platelet count. This model was tested in cancer patients classified by the Barcelona Clinic Liver Cancer (BCLC), Cancer of Liver Italian Program (CLIP) and Okuda systems, and was compared with other non-invasive models for predicting hepatocellular cancer.HCC-Mark produced a ROC AUC of 0.89 (95% CI 0.85-0.90) for discriminating hepatocellular carcinoma from liver cirrhosis in the estimation group and 0.90 (0.86-0.90) in the validation group (both p < 0.0001). This AUC exceeded all other models, that had AUCs from 0.41 to 0.81. AUCs of HCC-Mark for discriminating patients with a single focal lesion, absent macrovascular invasion, tumour size <2 cm, BCLC (0-A), CLIP (0-1) and Okuda (stage Ι) from cirrhotic patients were 0.88 (0.85-0.90), 0.87 (0.85-0.89), 0.89 (0.85-0.93), 0.87 (0.84-0.89), 0.85 (0.82-0.87) and 0.86 (0.83-0.89), respectively (all p < 0.0001).HCC-Mark is an accurate and validated model for the detection of hepatocellular cancer and certain of its clinical features.
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OBJECTIVE: To study the relationship between hepatocellular carcinoma and hepatitis B virus by reviewing the level of serum markers of hepatitis B virus in hepatocellular carcinoma cases and other cases without liver diseases.METHODS:The cases of hepatocellular carcinoma(224) and non-liver diseases(280) were sampled hospitalized in the First Affiliated Hospital of China Medical University.Then a case-control study was performed on serum markers of HBV and the history of hepatitis B,cirrhosis and so on of all the cases.RESULTS: The total infection rate of HBV in the heatocellular carcinoma cases was 68.22%(146/214) with 65.42%(140/214) of HBsAg and 30.84%(66/214) of anti-HBe,and 7.63%(20/262) in the non-liver disease cases.There was a significant difference(χ2=200.1,P0.000 1) on the total infection of HBV between the hepatocellular carcinoma cases and the controls,and the relative risk calculated was 27.4(95%CI 16.0-46.9).CONCLUSION: HBV is a major risk factor for hepatocellular carcinoma and PHC screening for people with HBV infection plays an important role in the PHC early diagnosis and improving therapeutic effect.
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Objective To analyze the morbidity of liver cancer and viral hepatitis B from 1988 to 2010 at Ninghe County in Tianjin.Methods The report date of the incidence of liver cancer and hepatitis B from 1988 to 2010 at County Ninghe were collected.The crude and standardized morbidity rate(SMR)was calculated.Results The SMR of liver cancer from 1988 to 2010 at County Ninghe was 22.43/100 000,which was nearly twice as much as the average level of liver cancer incidence(10.22/100 000)in Tianjin.The peak SMR was located at year 1990 to 2006,and then it declined.The incidence of hepatitis B was 2/100 000 in 1990 and it reached to the peak value of 43/100 000 in 2006.After vaccination against hepatitis B for whole residents at Ninghe county from January 2008 to September 2010,the incidence of hepatitis B in 2010 decreased by 36.2% than that in 2007.The rate in peasants dropped by 32.8%,the rate in students dropped by 22.2% and the rate in government staff dropped by 76.9%.The incidence of hepatitis B in government staff and students were lower than 1/100 000 and 4/100 000,respectively.Conclusion The incidence of liver cancer at Ninghe County was higher than the average level of Tianjin.The incidences of liver cancer and hepatitis B declined from 2007.
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The aim of this study was to determine the characteristics of hepatocellular carcinoma at a major health center in southern Turkey. Computed tomography was compared to the combination of ultrasonography and serum alpha-fetoprotein determination in the diagnosis of hepatocellular carcinoma.Of 226 patients with liver cirrhosis, 35 were diagnosed with hepatocellular carcinoma on first admission or during follow-up in the period between 1999 and 2002. The features investigated were, age at time of hepatocellular carcinoma diagnosis, etiology of cirrhosis, severity of cirrhosis at presentation, tumor pattern, stage of hepatocellular carcinoma, serum alpha-fetoprotein level, and dynamic computed tomography findings. Results were compared to previous findings in Turkey and elsewhere.In the hepatocellular carcinoma patients, the male:female ratio was 4:1 and the mean age at presentation was 61 years. Chronic hepatitis B virus infection (65.7%) and chronic hepatitis C virus infection (28.6%) were the most frequently identified risk factors for hepatocellular carcinoma. Forty percent of the patients had Child-Pugh A cirrhosis when they were diagnosed with hepatocellular carcinoma. Sixty-seven percent of patients had fewer than three hepatocellular carcinoma nodules in the liver at the time of diagnosis. Only three of the hepatocellular carcinoma cases were Okuda stage I. The combination of ultrasonography and serum alpha-fetoprotein >20 ng/ml identified hepatocellular carcinoma in 32 of the 35 total cases.The results indicate that hepatitis B virus infection in patients with cirrhosis is still the leading risk factor for the development of hepatocellular carcinoma. Also, early-stage hepatocellular carcinoma is rarely diagnosed in cirrhosis patients from this region of Turkey. Surveillance with computed tomography for early diagnosis of hepatocellular carcinoma seems not to be mandatory.
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Hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma in China. Epidemiological surveys show that male have a much higher incidence of hepatocellular carcinoma than female. Studies have shown that estrogen and its receptors are associated to gender disparity in hepatocellular carcinoma, but the underlying molecular mechanisms has not yet been fully elucidated. This article reviews the possible mechanisms of estrogen and its receptors in the occurrence and progression of hepatitis B virus-related hepatocellular carcinoma.在中国,乙型肝炎病毒(HBV)感染是肝细胞癌发生的最常见原因。流行病学调查显示男性肝细胞癌发病率明显高于女性。研究表明,雌激素及其受体与肝癌性别差异性相关,但其相关分子机制仍未完全阐明。现就雌激素及其受体在HBV相关肝癌发生和发展中的可能机制进行综述。.
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