Risk factors for hepatocellular carcinoma in a cohort infected with hepatitis B or C
The incidence of hepatocellular carcinoma (HCC) has increased in Australia in recent decades, a large and growing proportion of which occurs among a population chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, risk factors for HCC among these high-risk groups require further characterization.
We conducted a population-based cohort study using HBV and HCV cases notified to the New South Wales Health Department between 2000 and 2007. These were linked to cause of death data, HIV/AIDS notifications, and hospital records. Proportional hazards regression was used to identify significant risk factors for developing HCC.
A total of 242 and 339 HCC cases were linked to HBV (n = 43 892) and HCV (n = 83 817) notifications, respectively. For both HBV and HCV groups, being male and increasing age were significantly associated with risk of HCC. Increasing comorbidity score indicated high risk, while living outside urban areas was associated with lower risk. Hazard ratios for males were two to three times those of females. For both HBV and HCV groups, cirrhosis, alcoholic liver disease, and the interaction between the two were associated with significantly and considerably elevated risk.
This large population-based study confirms known risk factors for HCC. The association with older age highlights the potential impact of HBV and HCV screening of at-risk groups and early clinical assessment. Additional research is required to evaluate the impact of improving antiviral therapy on HCC risk.
Available from: Sebastian Mueller
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ABSTRACT: Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. However, there has been limited research investment into ALD despite its significant burden on the health of Europeans. This disparity is reflected by the ETOh score - the ratio of the estimated population mortality rate to the number of trials focused on a particular disease. The ETOh score for ALD is 358, compared with 1.4 for hepatitis B, 4.9 for hepatitis C, and 15.2 for primary biliary cirrhosis . In recent years however, the mechanisms driving disease progression and the natural history of ALD have been better defined and novel targets for therapy have been identified . In addition, significant clinical research has produced a clear framework for the evaluation of new therapies in particular in patients with alcoholic steatohepatitis (ASH). ALD is a complex disease, the successful management of which hinges on the integration of all the competences in public health, epidemiology, addiction behavior and alcohol-induced organ injury. Both primary intervention to reduce alcohol abuse and secondary intervention to prevent alcohol-associated morbidity and mortality rely on the coordinated action of multidisciplinary teams established at local, national, and international levels. These guidelines are largely based on the issues raised during the EASL monothematic conference on ALD held in Athens in 2010. The guidelines have three main aims: (1) to provide physicians with clinical recommendations; (2) to emphasize the fact that alcohol can cause several liver diseases (steatosis, steatohepatitis, cirrhosis), all of which may coexist in the same patient; (3) to identify areas of interest for future research, including clinical trials. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system . The strength of recommendations thus reflects the quality of underlying evidence. The principles of the GRADE system have been enunciated. The quality of the evidence in these clinical practical guidelines (CPGs) has been classified into one of three levels: high (A), moderate (B) or low (C). The GRADE system offers two grades of recommendation: strong (1) or weak (2) (Table 1). The CPGs thus consider the quality of evidence: the higher the quality of evidence, the more likely a strong recommendation is warranted; the greater the variability in values and preferences, or the greater the uncertainty, the more likely a weaker recommendation is warranted.
Hepatology 08/2012; 57(2). DOI:10.3350/cmh.2013.19.3.216 · 11.06 Impact Factor
Available from: PubMed Central
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ABSTRACT: Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk.
We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection.
The variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68-0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65-1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance.
The variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers.
PLoS ONE 04/2012; 7(4):e35145. DOI:10.1371/journal.pone.0035145 · 3.23 Impact Factor
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Mortality rates are elevated among heroin-dependent populations compared to the general population. Liver disease is emerging as an important contributor to mortality as the heroin-dependent population ages. Two major risk factors for liver disease are hepatitis C virus infection and chronic heavy alcohol use. Both of these are highly prevalent among heroin dependent people, but their relative contribution to liver-related mortality is poorly understood.
Data recording all prescriptions of opioid substitution treatment in New South Wales, Australia, 1997-2005, were linked to the National Death Index. Crude and standardised mortality rates and standardised mortality ratios were calculated for liver-related and other major causes of death. Frequency counts were obtained for viral hepatitis and alcohol mentions in underlying liver deaths.
There were 208 underlying liver deaths for a CMR of 72.4 per 100,000 py (95% CI 62.9, 82.9), and liver deaths occurred at 9.8 times the general population rate (95% CI 8.5, 11.2). There were increases in liver-related mortality over time. Viral hepatitis was mentioned in three-quarters (n=156, 76%), and alcohol in 43% (n=90) of underlying liver deaths.
Liver-related deaths were shown to be increasing in this heroin-dependent population, and the majority of these deaths involved chronic viral hepatitis infection. Increased uptake of treatment for hepatitis C virus infection is crucial to reducing the burden of liver-related mortality in this population. Hepatitis B vaccination, and screening of OST patients for alcohol use disorders and delivery of brief interventions as clinically indicated may also be of benefit.
Drug and alcohol dependence 12/2012; 131(3). DOI:10.1016/j.drugalcdep.2012.11.012 · 3.42 Impact Factor
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