Hepatocellular Carcinoma Hepatitis C Virus Research Articles

Prevalence of Hepatitis C Virus among the Healthy Blood Donors in the Department of Transfusion Medicine of a Teaching Hospital

Background: Hepatitis C virus (HCV) has been described as a significant causative agent of chronic hepatitis since its characterization in 1989. HCV may remain latent or become activated, leading to persistent infections and, in some cases, cirrhosis and hepatocellular carcinoma HCV is most commonly transmitted through direct contact with infected blood. Other, less common routes of transmission of HCV include sexual intercourse with infected individuals and mother to child transfer. Materials and Methods: This is a cross-sectional descriptive type study which was carried out in the Department of Transfusion Medicine of Rajshahi Medical College Hospital for six months from January to June 2014 to determine the prevalence of hepatitis C virus in the apparently healthy blood donors. All apparently healthy blood donors fulfilling the inclusion and exclusion were included in this study. The blood donors who were positive for anti-HCV antibodies were seropositive. Anti HCV antibody screened by ICT and confirmed by ELISA method. Results: Among 1712 apparently healthy blood donors, 36 (2.1%) donors were anti-HCV positive, and 1676 (97.9%) donors were negative. The mean age of the study patients was 34.05 years (SD = ± 8.79). 66.7% of the study patients were male, whereas 33.3 % of donors were female among the 36 blood donors. Conclusion: It is absolutely necessary to avoid the transmission of infection from repeat donors who are asymptomatic HCV positive. Policymakers and public health stakeholders need to introduce and implement further preventive measures targeting the routes of HCV transmission. TAJ 2021; 34: No-2: 24-31

Antiviral Therapy in Patients With Chronic Hepatitis C-related Hepatocellular Carcinoma Responding to Palliative Treatment.

Advances in hepatitis C virus (HCV) treatment offer high sustained virologic response rates with minimal side-effects. However, benefits of eradicating HCV in hepatocellular carcinoma (HCC) patients whose life expectancies are hard to be determined after palliative therapy still needs to be assessed. This study sought to evaluate prognostic factors for survival in HCV-related HCC patients that responded to the palliative HCC treatment to speculate whether treating HCV would be beneficial in these patients. In this retrospective cohort study, the medical records of 97 patients that showed complete or partial response to the initial HCC treatment were included. Receiving HCV treatment [hazard ratio (HR), 0.244; 95% confidence interval (CI), 0.075-0.788; P=0.018] increased the survival, whereas partial response to the initial HCC treatment (HR, 1.795; 95% CI, 1.071-3.008; P=0.026) and increased Child-Turcotte-Pugh score (HR, 2.017; 95% CI, 1.196-3.403; P=0.009) reduced the survival. From 97 patients, 16 patients were eventually treated for HCV. The mean time from the last HCC therapy to HCV treatment was 16.9±13.9 months. The median time of follow-up after HCV treatment was 10.0 months (range, 3 to 47 mo). Among the HCV-treated patients 3 patients had HCC recurred. The time to progression in HCV-treated patients were significantly longer than those untreated for HCV (P=0.032). Although treating HCV in HCC patient that undergo noncurative HCC treatment is still debatable, this study results carefully suggest that HCV-related HCC patients that responded to the initial HCC palliative treatment might benefit from HCV treatment.

Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide.

High-quality data on liver cancers by probable cause are scarce in many regions of the world. The United Nations recently set a goal of eliminating viral hepatitis as a major public health threat by 2030. We aimed to estimate the number of new cases of cancers attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) at a global, regional and country level, and by development status. We used data on the prevalence of HBV and HCV in hepatocellular carcinoma from a systematic review including 119,000 cases in 260 studies covering 50 countries. A statistical model was constructed to extrapolate empirical data to countries without prevalence data. Country-specific numbers of liver cancer cases attributable to HBV and HCV were calculated using data from GLOBOCAN 2012. Globally, 770,000 cases of liver cancer occurred worldwide in 2012, of which 56% (95% CI: 52-60) were attributable to HBV and 20% (95% CI: 18-22) to HCV. Currently, HBV causes approximately two out of three cases of liver cancer in less developed countries but one in four cases in more developed countries and shows a much higher degree of geographical aggregation in Eastern Asia and sub-Saharan Africa than HCV. These estimates help set priorities for liver cancer prevention. High-coverage HBV vaccination will be transformational in HBV-endemic countries but the prevention of HCV transmission and the treatment of chronic carriers of both viruses requires new scalable solutions.

Interest of variations in microRNA-152 and -122 in a series of hepatocellular carcinomas related to hepatitis C virus infection.

Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C virus (HCV) infection and constitutes the main burden of this disease. The molecular mechanisms underlying the development of HCC are multiple and might involve certain microRNA (miR). As discordant results have been reported concerning the detection of expression of miR-152 and miR-122 in HCC, our aim was to measure the levels of both miRs in serum and liver samples. We analyzed miR-152 and miR-122 expression by reverse transcription-quantitative polymerase chain reaction in a serum cohort from 14 HCV-infected patients who developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also studied miR-152 and miR-122 in an independent tissue cohort from 11 normal livers, and from paired HCC and non-tumor adjacent livers of 11 HCV-infected patients and 12 non-infected patients. In serum samples, higher levels of miR-122 were found in non-HCC HCV+ compared to HCC HCV+ and control groups, whereas miR-152 was detectable in a lower range in HCC HCV+ compared to non-HCC HCV+ and control groups. We found higher signals for miR-122 and miR-152 in non-tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma etiology had no detectable influence on miR-122 expression, whereas miR-152 was increased in HCV+ tissue samples. Detection of low values of circulating miR-152 is a potentially interesting marker of hepatocarcinogenesis in HCV+ patients, in contrast to miR-122, which varies according to hepatocyte damage.

World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti‐HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first‐generation enzyme‐linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker–negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV‐positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western‐Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV‐positive HCC. Conclusion: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV. (Hepatology 2015;62:1190‐1200)

Abstract SY34-01: Infection causing cancer: An update on the global burden

Abstract SY34-01: Infection causing cancer: An update on the global burden

High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C

Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk for the development of HCC increases with the severity of liver inflammation and fibrosis. The hepatic inflammation caused by HCV involves host regulatory immune response, which is mediated by cytokines with anti-viral role upon the interaction of viral polypeptides with innate and adaptive immunity. Two cytokines; tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) play key roles in the regulation of cellular immune response in HCV infection. The aim of the present study was to determine the levels of IL-10 and TNF-α, as well as the ratio of TNF-α and IL-10 serum levels in patients with HCV and HCC caused by HCV (HCC–HCV). The study included 173 patients with chronic HCV. TNF-α and IL-10 serum levels were measured by ELISA (R&D Systems, Inc.). In the present study, 54 patients presented liver mild fibrosis, 68 had severe fibrosis and 51 patients had HCC. After adjustment in the multivariate regression analysis, the following variables remained significantly associated with HCC–HCV occurrence: diabetes (p=0.012 OR 10.44 CI 1.66–65.60), IL-10 lower levels (p<0.0001 OR 0.83 CI 0.78–0.89) and TNF-α higher levels (p<0.0001 OR 1.19 CI 1.11–1.28). Individuals with HCC presented higher TNF-α/IL-10 ratio than those with fibrosis grade F4, F3 or F0+F1+F2 (p=0.0003, p<0.0001, p<0.0001, respectively). Patients with HCC were associated to higher index TNF-α/IL-10 ratio, suggesting that the unbalanced production of these cytokines may represent progression to the liver disease severity in HCV infected patients.

Hepatitis C Virus-Associated Primary Hepatocellular Carcinoma in Non-cirrhotic Patients

There is limited literature on hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of cirrhosis. To investigate the relationship between HCV and HCC in the absence of cirrhosis and to characterize patients with HCV infection presenting with HCC in the absence of cirrhosis. We identified all adult patients with histological confirmation of HCC between 1994 and 2007 (404 patients). A case-control design (four controls for each case with non-cirrhotic HCC) was chosen to compare characteristics and survival of HCV in HCC patients without (cases) and with (controls) cirrhosis. Conditional logistic regression analysis was used to identify factors independently associated with HCV in non-cirrhotic HCC. Eighty-seven patients with non-cirrhotic HCC were identified, six (7 %) had HCV infection in comparison with 107 of 317 (55.7 %) with cirrhotic HCC (P < 0.001). Compared with the HCV-associated HCC cirrhotic group, patients with HCV-associated HCC in the absence of cirrhosis were more likely to present with a single nodule (100 vs. 66.7 %), larger nodule size (>5 cm) (100 vs. 16.7 %), and macrovascular invasion (66.7 vs. 17.4 %) at time of diagnosis. Four of six patients with HCV-associated HCC in the absence of cirrhosis where alive at three years (all had resection), which was better survival than for HCC arising in cirrhotic livers of HCV-infected individuals (66.7 vs. 39.1 %). We found that HCV is responsible for a small minority of non-cirrhotic HCC cases representing an uncommon and poorly defined subgroup of HCC.

Acute and chronic hepatitis: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Acute and chronic hepatitis: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Viral loads and E2/NS1 region sequences of hepatitis C virus in hepatocellular carcinoma and surrounding liver.

ObjectivesNumerous epidemiologic data have documented that chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). But the molecular mechanism underlying these strong epidemiologic associations between HCV and HCC has not been elucidated. We observed the changes of HCV in HCC to investigate the association of HCV with HCC.MethodsWe used competitive and quantitative polymerase chain reaction and dideoxy-nucleotide chain termination method to compare HCV titers and sequences of the hypervariable region of E2/NS1 region of four isolates from the HCC and surrounding cirrhotic liver tissues in two anti-HCV positive patients.ResultsThe copy numbers of HCV-RNA were 1×106 and 4×106/gm wet weight of HCC, and 8×107 and 3.2×108/gm wet weight of cirrhotic liver tissues from patient-1 and -2. The sequence differences between HCV RNA in HCC and in cirrhotic liver were two and five nucleotides in patient-1 and in patient-2 respectively. The amino acid sequences were changed in one and two site in each patient.ConclusionThese findings may suggest the possible etiological role of HCV in carcinogenesis of HCC, but complete sequence analysis of HCV including multiple isolates in the same patient, should be performed in many cases.

Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma in Thailand

The prevalences of infections with hepatitis C virus (HCV) and hepatitis B virus (HBV) were determined in 110 Thai patients with liver cancer, of whom 80 and 30 had histological diagnoses of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), respectively. Hepatitis B surface antigen was detected in 63·8% of HCC patients and 16·7% of those with CCA. Antibodies to HCV, detected by a third-generation enzyme immunoassay, were found in 11·3% of HCC patients and in no CCA patient. HCV ribonucleic acid (RNA) was detected by polymerase chain reaction in 6 anti-HCV positive patients, and also in 2 patients who had no detectable anti-HCV antibody. A total of 11 patients had evidence of HCV infection, 8 of whom were infected with HCV alone. HCV genotypes were determined in all 8 patients who had HCV RNA; genotype 3a was the most common (62·5%). These results demonstrate that, in Thailand where both HBV and HCV are endemic, HBV infection is still the most important risk factor for HCC, but HCV also has an important role in those without HBV infection. In addition, the genotypic distribution of HCV in HCC in Thailand is similar to that in the general population. No specific association between genotype 1b and HCC was observed.

Detection of Different Quasispecies of Hepatitis C Virus Core Region in Cancerous and Noncancerous Lesions

The quasispecies of hepatitis C virus (HCV) core region in non-cancerous and cancerous hepatocellular carcinoma (HCC) lesions, respectively, of 7 patients with hepatocellular carcinoma were studied. Multiple fluorescence based-polymerase chain reaction (PCR)-single strand conformation polymorphism exhibited a different set and a larger number of quasispecies in cancerous portions than those in non-cancerous portions. DNA sequencing of PCR-amplified core region substantiated an accumulation of nucleotide substitutions, and a greater number of quasispecies in cancerous portions than those in non-cancerous portions. The deduced amino acid sequences disclosed that at the peptide position 45, Ser is dominant in non-cancerous lesions, and Gly in cancerous lesions, respectively. Thus, HCV in hepatocellular carcinoma includes a large number of specific quasispecies presumably due to their vigorous proliferation. A different set of quasispecies with the amino acid change is presumed to be related to the hepatocarcinogenesis.

Detection of hepatitis C virus RNA in hepatocellular carcinoma by in situ hybridization.

Hepatocellular carcinoma frequently is associated with chronic hepatitis C virus (HCV) infection. The presence of HCV in hepatocellular carcinoma has been detected by reverse-transcription polymerase chain reaction of antigenomic HCV RNA, a tissue-specific replicative form of the virus. Now, however, this method of detecting the presence of HCV has been invalidated by reports of antigenomic RNA in the blood or in peripheral blood mononuclear cells. In situ hybridization of HCV RNA was conducted with digoxigenin-labeled cDNA from the core region on surgical specimens of noncancerous and cancerous areas from 12 patients with chronic hepatitis C with or without cirrhosis associated with hepatocellular carcinoma. Several control experiments were also performed, including RNase digestion before hybridization, hybridization with the use of a negative control, and immunohistochemical staining of HCV-core protein. The in situ hybridization showed positive signals both in noncancerous and cancerous areas of the liver tissue in eight cases. Positive signals were confined to neoplastic cells and nonneoplastic hepatocytes. There were fewer HCV-positive cells in the cancerous area than in the surrounding noncancerous area. In situ detection of HCV presents direct evidence of HCV infection in the neoplastic cells of hepatocellular carcinoma and suggests that neoplastic cells may lose their affinity for HCV in the course of malignant transformation.