Todd Schneider, the founder of HepTech, has eloquently laid out his journey from health to illness and back again in The Founder’s Story on this website.
Todd was fortunate to have some of the most brilliant minds in medical science consulting personally with him in his efforts. In the beginning Todd focused on natural anti-viral compounds. However, testing on natural compounds eventually proved unsuccessful in eradicating the virus.
At the start of Todd’s journey years ago, fibrosis/cirrhosis of the liver was generally considered irreversible. However, over the years, not only was reversal of fibrosis/cirrhosis established as fact, but science has come to an understanding of the mechanisms and the triggers of fibrogenesis.
"Conversely, the progress in understanding hepatic fibrosis made since the seminal observations by authors in early issues of HEPATOLOGY has been very inspiring. Although the prospect of treating fibrosis is not new, the foundation upon which current strategies of antifibrotic therapies are built is far sturdier and more realistic. Studies of gene therapy using protease delivery…establish proof-of-principle that even dense scar can be resorbed. A trove of studies in animal models have defined dozens of potential antifibrotics worthy of clinical trials…. These observations, combined with solid evidence of fibrosis regression in humans after successful treatment of the underlying liver disease, augur well for accelerating progress. Therapies will be increasingly tailored to host genotype and disease-specific features, given in combination. Methods of defining the risk of fibrosis progression and the likelihood of treatment response will be established. The two most immediate hurdles—the development of better diagnostics to clarify end points in clinical trials, and the need to establish that an antifibrotic can halt or regress fibrosis even when the underlying disease is unchecked—will be surmounted. Considering how far the field has advanced in 25 years, these fantasies are sure to become fact before HEPATOLOGY celebrates its 50th anniversary."
Five years later, the predictions from that 2006 Hepatology editorial seem especially prescient. At present, the mechanism of HCV fibrogenesis has become clear. The role of increased oxidative stress through HCV-induced ROS production has been well established, as well the identification of the activation of NFkappaB as the fibrogenic trigger. Early on, Todd and his medical team kept abreast of this developing area of science and relied on the information. The team followed this important path of research into fibrosis reversal, and, now, the science in the literature and the science behind the Hepatitis Technologies Medical Food Protocol is convincing, accepted and unchallenged by alternative theories.
Oxidative stress was present in 61% of the patients, irrespective of age, gender, viral load, BMI, aminotransferase level, histology activity index (HAI) and HCV genotype. Insulin resistance and steatosis were evident in 80% and 70% of the patients, respectively. In the patients infected by HCV genotype non-3, but not in those with genotype 3 infection HOMA-IR (p<0.03), steatosis (p=0.02) and fibrosis (p<0.05) were higher in the subjects with oxidative stress than in those without. Multiple regression analysis revealed that, HOMA-IR (p<0.01), fibrosis (p<0.01) and oxidative stress (p<0.05) were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress (p<0.03) and HOMA-IR (p<0.02). Steatosis (p<0.02) and HAI (p=0.007) were also independent predictors of fibrosis.
In patients infected by HCV genotype non-3, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis.
We have read with interest the paper published in issue 2, volume 16 of World Journal of Gastroenterology 2010 by Nakamura et al, demonstrating that the antioxidant resveratrol (RVT) enhances hepatitis C virus (HCV) replication, consequently, they conclude that RVT is not a suitable antioxidant therapy for HCV chronic infection. The data raise some concern regarding the use of complementary and alternative medicine since the most frequent supplements taken by these patients are antioxidants or agents that may be beneficial for different chronic liver diseases. A recent study by Vidali et al on oxidative stress and steatosis in the progression of chronic hepatitis C concludes that oxidative stress and insulin resistance contribute to steatosis, thus accelerating the progression of fibrosis. We are particularly interested in investigating how the oxidative and nitrosative stress mechanisms are involved in the pathogenesis of different chronic liver diseases.
"Conclusions: Our data provide further evidence that HIV and HCV independently regulate hepatic fibrosis progression through the generation of ROS; this regulation occurs in an NFκB-dependent fashion. Strategies to limit the viral induction of oxidative stress are warranted to inhibit fibrogenesis."
Additionally, the Hepatitis C-induced increase in ROS production and the consequences of increased oxidative stress has been demonstrated in many independent studies.
Hepatitis C virus (HCV) is a blood-borne pathogen and a major cause of liver disease worldwide. Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection. Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism genes, which may contribute to oxidative stress. We also found that infection of chimeric SCID/Alb-uPA mice by HCV led to signs of hepatocyte damage and apoptosis, which in patients plays a role in activation of stellate cells, recruitment of macrophages, and the subsequent development of fibrosis. Infection of chimeric mice with HCV H77c also led an inflammatory response characterized by infiltration of monocytes and macrophages.
"In this study we have fed HCV infected mice an antifibrotic/antioxidant diet and examined their livers after 2 months of infection. The diet consisted of vitamins/cofactors and antioxidants designed to feed into the glutathione homeostasis cycle as well as direct antioxidants such as N-acetyl cysteine. During the course of infection viral titers were measured, and there was no change in mortality or the levels of HCV viral titers associated with the diet. The livers of infected mice on the diet were compared to the livers from infection and age-matched mice transplanted with the same donor liver cells. We found that there was a decrease in lobular inflammation, and an increase in portal inflammation. Notably there was a decrease in the amount of apoptosis as measured by Tunel reactivity in liver sections. There was a decrease in the number of activated stellate cells when liver sections were stained using antibodies specific for smooth muscle actin. Importantly there was a decrease in the amount of collagen I deposited in infected livers as measured by both Mason's tirchrome stain and quantitated using Picro Sirus Red staining. Thus it appears that the fibrosis induced by HCV in mice with chimeric mouse/human livers can be suppressed by an antioxidant diet."