Investigation of Relationship between Hepatitis B Virus and Gastric Adenocarcinoma.
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Abstract:
Dear Editor,
Gastric cancer is the second leading cause of cancer-related deaths worldwide [1][2][3] while some genetic and environmental factors such as infectious agents were shown to be linked to carcinogenesis.[2] Infectious agents notably viruses were shown to induce 20-25% of all cancers around the globe.[4][5] Helicobacter pylori (H. pylori) is one of those infectious agents to be related to gastric carcinogenesis.[1][2] Epstein bar virus was inconstantly demonstrated to be associated with gastric cancer that may be due to the presence of the cofactor of H. pylori that can immortalize abnormal epithelial cells.[6]
Hepadnaviridae, the most powerful infectious related cause of hepatoma has been reported with other malignancies such as renal cell carcinoma, gastric and oral cancers.[7][8][9] One study showed an association between anti-hepatitis C virus (HCV) antibody in 10.6% of sera of patients and gastric cancer.[10] Gastric cancer is assumed to be more prevalent in cirrhotic patients.[9] Expression of hepatitis B virus (HBV) antigens in H. pylori bearing gastric mucosa was shown by immunostaining methods.[11] Here we evaluated the association between HBV infection and gastric carcinoma in north of Iran.
We collected one hundred formalin-fixed paraffin embedded blocks of biopsies confirmed as gastric cancer in pathology department of our university belonging to patients who underwent gastrectomy during 2005-2010. Besides, 100 blocks of normal gastric mucosa tissues were provided as control group. Polymerase chain reaction for HBV DNA detection was performed.
Sixty nine percent of gastric cancer patients were male (Male/female ratio: 69/31) with a mean age of 67.14±10.98 years. The most common histological type of adenocarcinoma was intestinal type (68%) followed by diffuse (26%) and mixed (7%) types while the location was respectively proximal (57%), distal (22%) and diffuse (6%). The majority patients were diagnosed at advanced stage III (68%) followed by stage 2 (19%), stage 4 (9%) and stage 1 (4%). The most common grade was grade 2 (52%), grade 1 (41%) and grade 3 (7%).
HBV genome was undetectable in all cases and control subjects using PCR (Figure 1).
Fig. 1
Agarose gel electrophoresis illustrated a positive control for patients DNA (Beta actin as house keeping gene) compared to negative gastric cancer cases. 1: DNA ladder (50 bp-1000bp), 2, 3, 4, 5, 6, 7: Beta actin (321 bp), 8: Negative con-trol.
Previous studies confirmed the role of HBV in the pathogenesis of hepatocellular carcinoma.[4][5] Besides, limited studies have revealed association between HBV antigens and/or antibodies with other malignancies such as renal carcinoma, oral cancer, and gastric carcinoma.[7][8][9][10] Zullo et al. showed 2.6 folds increases in prevalence of gastric cancer in cirrhotic patients compared to non-cirrhotic individuals using endoscopic and histological examinations.[9]
Chen et al. showed the expression of HBV antigens in H. pylori infected gastric mucosa of patients with chronic liver disease using immunostaining.[11] Our findings showed that HBV genome was undetectable in gastric cancers. We demonstrated that HBV was not correlated with gastric carcinoma in north of Iran.Keywords:
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Abstract Background It has been proved that hepatitis B virus (HBV) infection alters the metastatic pattern and affects survival in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), while the influence of HBV infection on metastatic pattern and survival in patients with pancreatic cancer (PC) has not been investigated yet. Methods We conducted an investigation to evaluate the impact of HBV infection on metastatic pattern and overall survival in PC. We collected the data of 460 PC patients treated in our hospital from 1999 to 2010. Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact of HBV infection on metastatic pattern and overall survival was analyzed. Results We found that the incidence of synchronous liver metastasis was significantly higher in patients with HBsAg positive than those with HBsAg negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB) group than both non HBV infection and resolved HBV infection group (61.1% vs 33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What’s more, Kaplan-Meier analysis showed that CHB, resolved HBV infection and non HBV infection group had significant longer overall survival (OS) compared with inactive HBsAg carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the multivariate analysis, only the CHB and non HBV infection group had significant better overall survival compared with IC group (P=0.010 and P=0.018 respectively). Conclusions Our study found that HBV infection increased synchronous liver metastasis rate, and HBV infection status was an independent prognostic factor in PC patients.
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The relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child–Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori -infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child–Pugh A, 70% of Child–Pugh B, and 100% of Child–Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.
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Hepatocellular malignancy in young adults is a prominent feature of hepatitis B virus (HBV) infection in southern Africa. Here we report a cross-sectional study of liver pathology correlated with biomarkers in adults with HBV infection in Zambia. We analysed liver biopsies from Zambian patients with persistent HBV infection. We analysed 104 patients with HBV infection and evidence of liver disease. We obtained liver biopsies from 53 adults; of these, 12 (23%) were hepatitis B e antigen seropositive. The genotype was evenly distributed between A and E. One biopsy showed malignancy. Stage was 3 or more in 11 of 52 (21%) biopsies free of malignancy and lobular inflammation was found in 50 (94%). Neither alanine aminotransferase (ALT) nor the γ-glutamyl transferase:platelet ratio (GPR) were correlated with the stage of disease but were correlated with total Ishak score (ρ=0.47, p=0.0004 and ρ=0.33, p=0.02, respectively). Large cell change was observed in 10 of 11 biopsies with fibrosis stage 3 or more and 16 of 41 with early disease (p=0.005). Serum α-fetoprotein was elevated, although still within the normal range, in patients with large cell change (median 3.6 [interquartile range {IQR} 1.6–5.1]) compared with those without (1.7 [IQR 1.0–2.8]; p=0.03). Neither ALT nor GPR predicted large cell change. Large cell change was common in young HBV-infected adults in Zambia. Only serum α-fetoprotein was identified as a biomarker of this phenotype.
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We aimed to investigate the impact of hepatitis B virus (HBV) DNA on the development of hepatocellular carcinoma (HCC). We conducted a case/control study based on 506 chronic HBV patients followed up since 1997. Forty-one patients developed HCC, and each of them was age and gender matched with two simultaneously recruited controls without HCC. HBV DNA was measured at the initial visit, at yearly intervals, and at the last visit. Patient age at the time of HCC development was 55 +/- 9 years. Forty-nine (40%) patients experienced antiviral treatment. The median time from diagnosis to the development of HCC was 17 months, and the control patients were followed for 92 months. At the trough level (defined as lowest level among all studied visits), more (27 patients; 66%) HCC patients had HBV DNA levels of >10,000 copies/ml than the controls (17 patients; 21%). The area under the receiver operating characteristic curve of the trough log HBV DNA level for HCC was 0.79 (95% confidence interval [CI], 0.69 to 0.89). Trough log HBV DNA (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P < 0.0001) and liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P < 0.0001) levels were independently associated with HCC after an adjustment for age, gender, antiviral treatment, and HBV genotype. The difference in the trough HBV DNA level was more obvious among untreated patients (5.7 +/- 1.4 log copies/ml in HCC patients versus 3.2 +/- 1.3 log copies/ml in control patients; P < 0.0001) than among those who had received antiviral treatment (3.0 +/- 1.4 log copies/ml in HCC patients versus 2.5 +/- 0.9 log copies/ml in control patients; P = 0.38). A high trough HBV DNA level was associated with a higher risk of HCC. Whether antiviral treatment could prevent HCC was uncertain.
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Objective To analyze the seroprevalence of Helicobacter pylori (H. pylori) infection and its specific genes in liver tissues of chronic hepatitis B virus (HBV) infected patients, and to investigate the effect of H. pylori on development of chronic HBV infected liver diseases. Methods Five hundred and two patients infected with HBV and 429 sex-and age matched healthy controls were enrolled in the case-control study. All subjects were tested for presence of antibodies against H. pylori using ELISA. Fifty-six liver biopsy samples were amplified by polymerase chain reaction (PCR) using Helicobacter genus-specific 16S rRNA primers. The positive samples were further amplified using specific primers of H. pylori cagA, vacA and glmM genes. Results H. pylori infection was accounted for 63.9% in HBV infected patients, which was higher than that in healthy controls (43.4%,P<0.05). Moreover, the seroprevalence of H. pylori in patients with hepatocellular carcinoma (HCC, 29/36,80.6%) or cirrhosis (64/83,77.1%) was higher than that in patients with chronic hepatitis (228/383,59.5%, P<0.01). Helicobacter genus-specific 16S rRNA was found in 17,7 or 11 of patients with cirrhosis, HCC or chronic hepatitis. Twenty-one samples were confirmed as H. pylori DNA by PCR. Conclusions The seroprevalence of antibody against H. pylori was higherHelicobacter can be detected in liver tissues of HBV infected patients. H. pylori might play the role in the development in HBV infected patients compared with healthy controls. Besides H. pylori, other of chronic hepatitis to cirrhosis and HCC.
Key words:
Helicobacter pylori; Hepatitis B; Live cirrhosis; Live neoplasms
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Hepatitis B virus (HBV) is an important public health problem worldwide. Chronic HBV in patients undergoing chemotherapy and immunosuppressive treatment are at risk of HBV reactivation. The consequence of HBV reactivation in immunosuppressed patients may lead to liver failure and death. Therefore, this study was conducted to investigate the frequency of HBV markers in cancer patients before chemotherapy.In this study cross-sectional, blood samples were collected from 90 cancer patients before chemotherapy. The patient's sera were tested for the presence of HBsAg and anti-HBc using enzyme-linked immunosorbent assay (ELISA). The HBVDNA was tested for patient's sera using nested polymerase chain reaction (nested-PCR).Among 90 patients, 42(46.7%) were males and 48 (53.3%) females, with a mean age of 52.52 ± 11.71 years (range, 25-83 years). Of the 6/90 (6.66%) patients, including 4/42 (9.5%) males and 2/48 (4.1%) females cases were positive for HBsAg, anti-HBc and HBV DNA, (P=0.31). The frequency of HBV infection in cancer patients was rectal 3(3.33%), breast cancer 2 (2.22%) and prostate 1(1.11%) cases. The sera of 8/84 (9.52%) patients including 5/39 (12.82%) males and 3/45 (6.66%) females tested positive for anti-HBc, but negative for HBsAg and HBV DNA. (P=0.55). The results of phylogenetic tree revealed that four isolated HBV DNA in cancer patients were cluster with genotype D.High frequency of 6.66% HBV infection have been observed in cancer patients before chemotherapy. The sera of 9.52% patients were only positive for anti-HBc IgG which may indicate the past HBV infection or presence of OBI but requires further investigation. To prevent HBV or OBI reactivation, the screening of HBV DNA and anti HBc should be implemented for cancers patients before chemotherapy.
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Objective To investigate the relationship between the genotypes of hepatitis B virus and the clinical and liver pathological features of patients with chronic hepatitis in the Zhoushan Islands. Methods One hundred eighty HBV DNA positive chronic hepatitis patients with HBV markers were enrolled in this study. They were at least second generation Zhoushan Island residents. One hundred forty-seven of them were males and 33 were females with an average age of 39.0+/-11.3. Among the 180 patients, 17 had ASC, 57 had mild CHB, 48 moderate CHB, 9 severe CHB, 6 SHB, 39 LC, and 4 had HCC. The genotypes of their serum HBV were detected by using PCR integrated with Tagman MGB probe technology, and their serum HBV markers, HBV DNA and liver functions were also examined. Out of 180 patients, 129 accepted a liver biopsy. A pathological evaluation was then performed. Results HBVs of genotype C, 135 cases (75.0%), of B, 40 cases (22.2%), and of B+C, 5 cases (2.8%) were found among these 180 patients. No genotype A or D HBV were found. The proportions of genotype C virus were 7/17, 86/114, 34/39, 6/6 in ASC, CHB, LC and SHB patients. In the hepatocellular carcinoma patients, there were 2 each of genotype B and C. Among the 99 patients with genotype C HBV, 84 cases (84.8%) showed moderate and severe inflammation histologically in their livers and among the 30 patients with B, 7 cases (23.3%) showed moderate to severe inflammation in their livers (z = 6.47, P less than 0.01). The proportion of genotype C HBV was significantly different from that of genotype B HBV in those that showed moderate and severe (S3-4) liver fibrosis. In patients infected with genotype C HBV who had moderate and severe liver pathological changes, their clinical manifestations reflected better the histological alterations of their livers. Conclusion Genotypes C, B and B+C HBV were found in CHB patients in the Zhoushan Islands of China, and type C was the predominant one. The liver pathological damage level of genotype C HBV infected patients is more serious than that of genotype B.
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Several non-hepatocellular cancers were linked with hepatitis B virus (HBV) infection. This study was aimed to quantify the potential associations between HBV infection and multiple non-hepatocellular cancers. Continuous cases, including 5,715 non-cancer and 40,963 cancer cases diagnosed from 2008 to 2014 in Sun Yat-sen University Cancer Center were analyzed. HBV DNA and hepatitis B core antigen (HBcAg) were examed in gastric cancer tissues by polymerase chain reaction and immunohistochemical staining. After adjusting for age, sex, year of diagnosis, smoking, drinking and family history of cancer, significant associations were found between serum HBsAg and frequently reported HBV-related non-hepatocellular cancers, including non-Hodgkin's lymphoma, cholangiocarcinoma and pancreatic cancer [adjusted odds ratio (AOR) and 95% confidence interval (CI): 1.89 (1.65-2.16)], as well as total other non-hepatocellular cancers [AOR and 95% CI: 1.12 (1.03-1.22)]. The median ages at diagnosis, all-cause death and cancer-specific death of serum HBsAg positive cancer patients were all significantly younger than those with serum HBsAg negative. HBV DNA was detected in 12.4% (34/275) gastric cancer tissues and HBcAg was most commonly detected in lymphocytes. This was the first report that HBV infection had a modest but significant nonspecific association with total non-hepatocellular cancers. Median age at diagnosis and death was significantly younger in serum HBsAg positive cancer patients. The underlying mechanism needs further investigation.
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We have examined the relationship between hepatitis B virus infection and hepatocellular carcinoma in a series of 50 British patients with histologically-proven hepatocellular carcinoma. Serum HBsAg was detected in 10 patients (20 per cent), and of the remainder, 21 per cent of those tested had serological evidence of past hepatitis B virus exposure. None of nine tumour specimens from serum HBsAg negative patients had detectable HBV-DNA integration into the tumour cell genome. The presence or absence of serum HBsAg was of no prognostic significance in British patients with hepatocellular carcinoma. Liver cell dysplasia, a possible pre-malignant lesion, was noted in 53 per cent of patients who had had liver biopsies before the diagnosis of hepatocellular carcinoma, and in 79 per cent of biopsies taken at the time of diagnosis of hepatocellular carcinoma. The presence of liver cell dysplasia was not more common in serum HBsAg positive patients.
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