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Hepatitis B viral load affects prognosis of hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself. The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function. Hepatitis B virus (HBV) is an established major risk factor of HCC development, and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC. High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways. First, it is associated with more frequent recurrence of HBV-related HCC after treatment. Second, it is associated with more occurrence and severity of potentially life-threatening HBV reactivation. Last, it is associated with more worsened liver function, which limits the therapeutic options for HBV-related HCC. HBV, directly or indirectly, can induce hepatocarcinogenesis. In patients with a high HBV DNA level and subsequent active hepatitis, adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis. HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes. Thus, high HBV viral load can affect the prognosis of patients with HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression. Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC. Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression, it is expected that long-term antiviral therapy results in the sustained HBV suppression, control of inflammation, reduction in HCC progression, and eventually in improved overall survival.

SUBMITTER: Yu SJ

PROVIDER: S-EPMC4161792 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Hepatitis B viral load affects prognosis of hepatocellular carcinoma.

Yu Su Jong SJ Kim Yoon Jun YJ

World journal of gastroenterology 20140901 34

Hepatocellular carcinoma (HCC) is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself. The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function. Hepatitis B virus (HBV) is an established major risk factor of HCC development, and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC. High HBV viral load may affect the pro ...[more]

PMID: 25232241

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Project description:BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen-positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels.RESULTSDuring a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00-5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00-7.99 log10 IU/mL, 6.00-6.99 log10 IU/mL, or 5.00-5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.

Project description:Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10(6) copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.

Project description:In Myanmar, over five million people are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Hepatitis has been a recent focus with the development of a National Strategic Plan on Hepatitis and plans to subsidize HCV treatment.During a two-day national liver disease symposium covering HCV, HBV, hepatocellular (HCC), and end-stage liver disease (ESLD), physician surveys were administered using the automated response system (ARS) to assess physician knowledge, perceptions of barriers to screening and treatment, and proposed solutions. Multivariate logistic regression was used to estimate odds ratio (OR) relating demography and practice factors with higher provider knowledge and improvement.One hundred two physicians attending from various specialty areas (31.0% specializing in gastroenterology/hepatology and/or infectious disease) were of mixed gender (46.8% male), were younger than or equal to 40 years old (51.1% 20 to 40 years), had less experience (61.6% with ≤10 years of medical practice), were from the metropolitan area of Yangon (72.1%), and saw <10 liver disease patients per week (74.3%). The majority of physicians were not comfortable with treating or managing patients with liver disease. The post-test scores demonstrated an improvement in liver disease knowledge (9.0% ± 27.0) compared to the baseline pre-test scores; no variables were associated with significant improvement in hepatitis knowledge. Physicians identified the cost of diagnostic blood tests and treatment as the most significant barrier to treatment. Top solutions proposed were universal screening policies (46%), removal of financial barriers for treatment (29%), patient education (14%) and provider education (11%).Physician knowledge improved after this symposium, and many other needs were revealed by the physician input on barriers to care and their solutions. These survey results are important in guiding the next steps to improve liver disease management and future medical education efforts in Myanmar.

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Hepatitis B viral load affects prognosis of hepatocellular carcinoma.

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Hepatitis B viral load affects prognosis of hepatocellular carcinoma.

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