Viral Hepatitis in the Canadian Inuit and First Nations Populations

OBJECTIVE: To review published prevalence data regarding hepatitis A (HAV), B (HBV) and C (HCV) in Canadian Inuit and First Nations populations

Different effects of rat interferon alpha, beta and gamma on rat hepatic stellate cell proliferation and activation

BACKGROUND: Liver fibrosis is the common sequel of chronic liver diseases. Recent studies have identified hepatic stellate cells as the primary cell type mediating hepatic fibrogenesis. It has been demonstrated that hepatic stellate cells undergo a process of activation during the development of liver fibrosis. During the activation process, hepatic stellate cells acquire myofibroblast-like phenotype featuring the expression of smooth muscle alpha actin. Interferons have been employed for the treatment of viral hepatitis. However, it is unclear what is the effect of interferons on the prevention and treatment of liver fibrosis. Moreover, it is not clear whether there are any differences among interferon alpha, interferon beta, and interferon gamma in the treatment of liver fibrosis. Therefore, our objective in current study is to investigate the effects of rat interferon-α, interferon-β, and interferon-γ on the proliferation and activation of rat hepatic stellate cells. RESULTS: Rat interferon-β and interferon-γ significantly inhibited rat hepatic stellate cell proliferation while rat interferon-α did not affect the cell proliferation under the same culture condition. Inhibition of cell proliferation was confirmed by both WST-1 cell proliferation assay and 5-bromo-2'-deoxy-uridine incorporation assay. Similar results were observed regarding interferons regulation of hepatic stellate cell activation. Both rat interferon-β and interferon-γ reduced smooth muscle α-actin abundance after 6 days treatment, but rat interferon-α did not alter smooth muscle α-actin level. CONCLUSIONS: Our results indicate that rat interferon-α and interferon-β have different biological effects on rat hepatic stellate cells and suggest that there are different signaling events between interferon-α and interferon-β in hepatic stellate cells

Evidence of Hepatitis B Virus Infection in Cancer and Noncancer Stem Cells Associated with Human Hepatocellular Carcinoma

Both the hepatitis B virus (HBV) and cancer stem cells (CSCs) have been independently implicated in the pathogenesis of hepatocellular carcinoma (HCC). To date, there have been no reports describing HBV infection within CSCs. In this report we describe HBV core (HBcAg) and HBx protein expression within CSCs associated with human HCC. HBV markers were also identified in nonmalignant stem cells present in adjacent nontumor tissue. These findings provide new insights into the pathogenesis of HBV-induced HCC and are potentially relevant to the treatment of both HCC and chronic HBV

Autoimmune Chronic Active Hepatitis (Lupoid Hepatitis) and Primary Sclerosing Cholangitis in Two Young Adult Females

Autoimmune chronic active hepatitis (CAH) and primary sclerosing cholangitis (PSC) arc chronic diseases of the hepatobiliary system that have many clinical, immunologic and genetic features in common. Despite these similarities, there are few reports of the two diseases coexisting. Two young women with clinical, biochemical, serologic, radiologic and histologic findings compatible with both autoimmune CAH and PSC are described. The observation that there may be a striking overlap in the features of these two diseases and recent improvements in diagnostic imaging of the biliary tract suggest that the association of these two diseases in the same individual may be more common than is presently appreciated

Principles in the Management of Chronic Hepatitis B Viral Infection

Recently licensed and promising new experimental agents should have a profound impact on the treatment of patients with chronic hepatitis B virus (HBV) infection. However, certain management principles should remain unaltered. Recognizing the need for more urgent treatment in some individuals, being able to identify which patients require treatment and those who are most likely to respond to treatment, and selecting the optimal timing for treatment are clinical decisions that must continue to be addressed regardless of the antiviral agent ‘of the month’. This review outlines general principles and provides a generic, timeless approach to the management of patients with chronic HBV infection

Hepatitis B Viral Mutants and Their Relevance to the Canadian Health Care System

Over the past 10 years, an increasing number of mutations in the hepatitis B virus genome have been described. While the majority of these mutations appear to be ‘silent’ or not clinically relevant, some have been described in association with increased severity of disease (core and basic core promoter mutations), evasion of immunological surveillance (S escape mutants), hepatocellular carcinogenesis (X mutants) and resistance to antiviral agents (DNA polymerase mutations). The molecular events and the clinical consequences thereof are reviewed

Think Stop before Going 'Off-Label'

Only after careful and extensive review of all available safety and efficacy data derived from preclinical and clinical trials will a regulatory body approve the licensing of a drug for a specific medical condition ('indication'). Experience with thalidomide, fialuridine and troglitazone, to name a few, reveal that despite these efforts, the process is not infallible. What then can we expect when a drug is used for a medical condition in which no such review process has been undertaken ('offlabel' use of the drug)