Healthcare, patient groups oppose hep-C drug patents
MUMBAI: Healthcare aid and patient groups have come together in patent courts to fight against ``abusive strategies'' of Big Pharma, to ensure access to affordable treatment in hepatitis C. The Initiative for Medicines, Access & Knowledge (I-MAK) together with Delhi Network of Positive People and international medical humanitarian organisation, Medecins Sans Frontieres filed three cases on crucial new hepatitis C medicines: two patent challenges on daclatasvir, one on velpatasvir and a further challenge on sofosbuvir.
The patent challenges could remove barriers to production and distribution of affordable generic versions of direct-acting antiviral (DAA) medicines, including Gilead's sofosbuvir and velpatasvir, and Bristol-Myers Squibb's daclatasvir.
Hepatitis C virus (HCV) infection remains one of the most common etiologies of liver disease worldwide. A number of epidemiological papers have addressed the global prevalence of Hepatitis C. Lanini et al reported that 100 million people globally have serological evidence of current or past HCV infection causing 700000 deaths annually while others suggest that the actual occurrence is double. HCV remains the most common indication for liver transplantation in the United States. Chronic infection with HCV can lead to liver inflammation, liver fibrosis, cirrhosis, and hepatocellular carcinoma.Figure 1 Vitamin D metabolism.
Liver fibrosis is a result of excessive accumulation of extracellular matrix proteins, as part of the wound healing response to chronic injury and chronic inflammation. Various factors have been associated with progression of fibrosis including duration of infection, age, male sex, diabetes, alcohol consumption and human immunodeficiency virus (HIV) co-infection.
Vitamin D is a hormone that has numerous biological properties that influence host physiology by regulating epigenetic regulation of more than 2000 genes throughout the body. Vitamin D is best known for its role in maintaining bone mineralization but has diverse and profound influences which can determine disease development and outcome. Although referred to as a vitamin, this steroid hormone is synthesized in the body by a series of hydroxylation reactions that occur in skin (7-hydroxylation), the liver (25-hydroxylation) and the kidney (1-hydroxylation) (Figure 1). Reduction of the enzymatic conversion of 7-dehydrocholesterol to 1.25 hydroxy vitamin D at any of the three conversion steps can result in suboptimal vitamin D status.
Vitamin D has a number of influences on innate and adaptive immunity which are pertinent to study in conditions that are driven by chronic inflammation and maladaptive tissue injury[8,9]. Given the ubiquitous distribution of vitamin D receptors in virtually every cell in the body-suboptimal vitamin D status has been studied for its relationship to numerous diseases.
For example, there is substantial evidence that vitamin D benefits rheumatoid arthritis, due to its immunomodulatory effect. The role of vitamin D in various cancers has been established linked to its antiproliferative action mediated through vitamin D nuclear receptor. There have been numerous reports on lower serum vitamin D levels in patients with chronic liver disease from various etiologies. In chronic HCV, Low vitamin D levels have been reported in 46% to 92% of patients raising suspicion of its potential contribution to disease pathogenesis.
There is growing evidence from various groups, that vitamin D levels are inversely correlated with liver inflammation and stage of liver fibrosis in patients with HCV; however, the studies are heterogeneous with occasionally the results are conflicting. Additionally, the methods of reporting liver fibrosis were variable.