Nicole Cutler L.Ac.

March 17, 2008
People with Hepatitis C can slow the liver’s cycle of inflammation by making these three healthy lifestyle changes. By eliminating certain risk factors, one can live a long life with HCV.

The number of people affected by Hepatitis C continues to grow. Unfortunately, the medicines used to treat this virus have not yet been able to defeat it. As of 2008, the current standard of treatment for the Hepatitis C virus (HCV), pegylated interferon and ribavirin, remains effective for approximately only half of all cases. Although pegylated interferon and ribavirin can’t help millions of people get rid of this virus, Hepatitis C doesn’t have to be a death sentence. Even though those living with chronic HCV are at a high risk of developing liver cirrhosis and/or liver cancer, eliminating three vices can prevent a worsening of liver health.

Understanding Liver InflammationLiving with chronic HCV means constantly battling liver inflammation. If this inflammation rages unabatedly, it causes liver disease to progress. The progressive cascade of Hepatitis C and liver inflammation is as follows:

• HCV results in the death of liver cells.
• The death of liver cells triggers the dispatching of inflammatory cells to the affected area. Inflammation begins the processes that lead to fibrosis, the body’s response to liver damage.
• Inflammation triggers a reaction by a group of cells in the liver called stellate cells.
• Infected and inflamed liver cells release chemical signals (called cytokines), which activate leukocytes (white blood cells) from outside the liver to travel to the affected area.
• The cytokines and leukocytes team up with Kupffer cells to signal the stellate cells to produce and lay down collagen fibers between liver cells. A fibrous protein that forms scar tissue, collagen is the body’s attempt to limit the spread of infection to other cells.
• Normally, as an infection or injury resolves, the collagen matrix enclosing the injury is dissolved and activated stellate cells die off, allowing the tissue to return to normal. In chronic HCV, this matrix of collagen grows more rapidly than it can dissolve.
• The collagen builds up scar tissue around cells causing living liver cells to lose their access to the nutrient and oxygen rich blood flow.
• The restricted access to blood causes even more quarantined liver cells to die. As such, HCV progressively scars the liver.

This vicious cycle of inflammation causing scar tissue must be stopped to prevent a person’s chronic HCV from causing more and more liver damage.

Vice EliminationAccording to Norah Terrault, MD, MPH, from the University of California, San Francisco, “Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise. It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”

By eliminating three unhealthful habits, people with HCV can single-handedly reduce the inflammation their liver must contend with. Although any toxin puts a greater strain on liver function, the following directly contribute to heightened inflammation with HCV:

1. Alcohol – There are many reasons why eliminating alcohol is imperative for living long with Hepatitis C. Researchers have demonstrated that alcohol promotes proliferation of Hepatitis C in human liver cells. Researchers at the Children’s Hospital in Philadelphia found that alcohol increases the activity of a protein called nuclear factor kappa B, which causes HCV to replicate. Aside from the cycle of inflammation that occurs with Hepatitis C, alcohol consumption on its own increases cytokine levels. Additionally, metabolized alcohol is believed to activate stellate cells directly. All of the chemical processes that occur when a person drinks alcohol exponentially worsen the damage that HCV does to the liver.
2. Marijuana – According to a study published in Clinical Gastroenterology and Hepatology, patients with HCV should not use marijuana (cannabis) daily. The researchers led by Terrault found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis.
3. Fatty Food – Despite campaigns claiming that eliminating saturated fat from the diet preserves heart health, hepatologists agree that it also preserves liver health. Research from 2007 demonstrated that a high fat diet kills regulatory T cells in the liver. Less of these specialized immune cells allow a fatty liver to worsen to steatohepatitis, fatty liver with inflammation. This likely occurs because regulatory T cell death is associated with increased inflammatory cytokine production.

Although removing these three vices from one’s life may be a monumental life change for someone, it can also save their liver. The increase in inflammation that drinking alcohol, smoking marijuana and eating saturated fat can cause allows a liver with HCV to spiral into advanced liver disease. By abandoning these three unhealthful habits, the liver gets a respite from the inflammation cycle – perhaps enough for the body to break down some of the collagen matrix that contributes to the continuation of liver cell death.

BY TIM SANDLE
integrates into mitochondria….."result of the failure to mount an efficient immune response to eliminate infected hepatocytes…..Our findings implicate the mitochondrial quality control pathway as a potential therapeutic target against HCV infection and associated liver disease pathogenesis")


Scientists have identified why people with the hepatitis C virus get liver disease and why the virus is able to persist in the body for so long. The answer is that the virus attacks the liver cells' energy centers. The hepatitis C virus appears attempt at attacking a liver cell structure called the mitochondria. Mitochondria are found in every cell in the human body; they are responsible for creating more than 90 percent of the energy needed by the body to sustain life and support growth

 

   
By attacking the mitochondria, the virus appears to dismantle the cell's innate ability to fight infection. Cells recognize the damage and respond to it by recruiting proteins that tell the mitochondria to eliminate the damaged area, but the repair process ends up helping the virus to replicate and infect other cells.
   

Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV). Chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or liver cancer. The virus is spread is spread primarily by blood-to-blood contact associated with intravenous drug use, poorly sterilized medical equipment, and transfusions.



The new research suggests that suggests that mitochondrial operations could be a therapeutic target against hepatitis C, the leading cause of liver transplants and a major cause of liver cancer in the U.S.

 



The study was carried out at the University of California, San Diego School of Medicine. The findings have been published in the journal Proceedings of the National Academy of Sciences, in a paper titled “Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence”.



Read more: http://www.digitaljournal.com/science/clue-for-hepatitis-c-survival/article/381437#ixzz2zEfRwd8C

 

 

Patients always want to know when a viral load is "too high". The fact is, although current treatment seems to go better when the viral load is initially lower, viral load does not correspond to level of sickness.

It is a fact there are people with viral loads of 30 million who feel fine and have little damage (as shown by biopsy) and others who have a viral load of 200,000 who can't get out of bed because they are so weakened.

For this fact, it's no wonder Hepatitis C is so baffling. There is no number that indicates how sick one is going to be in one year, five years or twenty years.

This is why, whether choosing to treat with current therapy or not, we recommend everyone protect and support their liver through dietary and lifestyle changes (as well as liver-specific nutritional supplementation).



Editors@Hepatitis-Central.com
www.Hepatitis-Central.com

What is Viral Load?

by: Albrecht Ernst

Your viral load is the amount of specific viruses that you have, in a given volume of your blood (usually 1 milliliter = 1 cubic centimeter). More precisely, it means that the amount of Hep C genetic material found in your blood corresponds to as many Hep C viruses as the given number says. Therefore the given number denotes "viral equivalents."

There appears to be no significant correlation between HCV RNA levels and ALT values or histological activity in patients untreated by anti-viral therapies (Interferon). Viral load varies between infected individuals but is not a useful prognostic indicator nor does it measure the severity of virus-induced liver disease.
 

WHAT DOES NEGATIVE OR "NOT DETECTED" MEAN?
 

The viral load can range from "not detected" to hundreds of millions. The meaning of "not detected" or "negative" differs, depending on the test used. In one lab, the detection limit for the *quantitative* HCV RNA test by *PCR* is 200 virus equivalents/ml (and with the *qualitative* test they can detect down to 10 virus equivalents/ml). The less expensive quantitative *bDNA* test has a detection limit of about 200,000 virus equivalents/ml. So it is less sensitive, but above its detection limit it is more accurate than the PCR test.

So, when you are "negative", maybe you have no Hepatitis C virus in your blood. But maybe also, you do have Hepatitis C virus in your blood, but the number of viruses is lower than the detection limit. {Example: If the less expensive quantitative *bDNA* has been used, and the detection limit is 200,000 virus equivalents/ml, any number less than this would register as "negative" or "not detected", when in fact, the viral load could be present, but less than this detection limit.} Your lab can tell you which testing measure is used, and your doctor can explain what it means in your case.
 

WHAT DOES "POSITIVE" MEAN?
 

When you get back the result of your HCV RNA quantitative test, and when the lab was able to determine the amount of virus in your blood, then it is important to write down not only the number, but also in what units this number is given.

I) Volume

The volume of blood, that the number refers to, is usually one milliliter.

But some labs give the number for 20 microliters = 1/50 milliliter. So in these cases you have to multiply the result of the viral load by 50 to get the number for 1 milliliter.

II) Amount of Virus

Unfortunately, there are several ways to express the viral load. So, in order to be able to compare different results, you have to know how to convert these numbers to some standard format, which let's say is just the plain number of viruses per milliliter, like 1.5 Million/ml, or 1,500,000/ml. (both of these numbers are the same).

a) Measure by weight

Sometimes, the lab reports the amount of genetic material found by its weight. 1 pg (pico-gram) of genetic material corresponds to about 1 million virus equivalents, so, if your lab result is given in picograms, just multiply the lab result by 1,000,000, and you have the number of viruses.

b) Measure by virus count

i) Plain numbers

Often the virus count is expressed as a plain number, like 1.73 million, or 1,730,000 or 1730000. Millions sometime are abbreviated by the prefix "M" (Mega). So when you see 1.73 Meq/ml, it means 1.73 Mega-equivalents/ml or again 1730000 equivalents/ml..

ii) Exponential format

Large numbers are often expressed in exponential form, that means a number, multiplied by 10 with an exponent. To convert this to normal numbers, append as many zeroes to a "1" as the exponent says, and multiply this with the number. In some lab report, the viral load was "Hep C RNA Quant 17.3 x 10(exp) 5 equivalents/ml". So, with 5 as exponent, you have to append 5 zeroes to a "1", that gives 100000, and multiply this with the number 17.3, that gives 1730000 as the viral load. Normally this would be written 1.73x10(exp)6, or 1.73x106 , (which are again the same number).

17.3x105 = 1.73x106 = 1,730,000

iii) Logarthmic format

Now, recently some people express these numbers also in logarithmic form (logarithmic transformed number).

log(1730000)=6.24

6.24 is the logarithmic transformed number of the viral load of our above example. A result of 3.5 for a viral load, that someone reported, seems to be such a number (unless he forgot to write down a "10" and an exponent). You need a calculator to convert this. You have to use the function 10x , where you have to replace x with the logarithmic number, in the above case 3.5. The result would be: 103.5 = 3162 virus equivalents per milliliter.

When you take the logarithmic number from the first example, 6.24, you have to calculate 106.24 = 1730000 , and here we have the original number of virus equivalents again. If you don't have a calculator, you can estimate the order of magnitude of a viral load expressed as a logarithmic number. From the logarithmic number, you take the first digit (left of the point) and add 1 to this number. This gives you the number of digits that your viral load has (expressed as a plain number).

Example: Logarithmic number 6.24

Left of the point is "6". 6+1 = 7

The number that gives the viral load is 7 digits long, that means it is between 1,000,000 and 9,999,999 (digit # 1 234 567)

The next digit (right of the point of the logarithmic number) shows whether you are high or low in the range.

In case you have a logarithmic number *and* a blood volume other than 1 ml, you have to convert the logarithmic number to a plain number *first*, and then correct it to correspond to 1 ml !

Therefore it is important to have a close look at your lab report and see in what units the result is given!


There is still no general agreement on what Viral Load is considered low and what is high in Hepatitis C. This interpretation makes sense for people not currently being treated - for someone who is 6 months into an INF + RIBA trial, even 200,000 could be considered a high titer.

(Numbers are Virus Equivalents per Milliliter)

below 200,000 very low (undetectable by *bDNA* test)

200,000 to 1,000,000 low

1,000,000 to 5,000,000 medium

5,000,000 to 25,000,000 high

above 25,000,000 very high

 

International Conference on Viral Hepatitis (ICVH) 2014Benjamin Young, MD, PhD, Natasha K. Martin, PhD, Thomas C.S. Martin, BMBCh, MRCP

A Reinfection With Hepatitis C

Benjamin Young, MD, PhD: Hello. I am Dr. Benjamin Young, Vice President and Chief Medical Officer of the International Association of Providers of AIDS Care. We are here in New York at the International Conference on Viral Hepatitis to have a discussion about reinfection with hepatitis C virus (HCV) and whether this might be a limiting factor in treatment and prevention programs.

I am very pleased to be joined today by Thomas Martin, who is an academic clinical fellow at the Chelsea and Westminster Hospital in London, and Natasha Martin, a theoretical mathematician from the University of Bristol.

The two of you gave a riveting panel discussion[1] just a few minutes ago. I want to bring this discussion to our audience. We have seen tremendous advances in the options for the treatment of HCV. They offer many possibilities, including what we know about HIV treatment, as a way of preventing new infections and limiting the extent of the HCV epidemic.

Let's talk about some of your recent work on reinfection with HCV and what this means. How big a problem is it in your communities, and what do you know about how this affects the prospects of treatment as prevention?

Reinfection in Injection-Drug Users and Men Who Have Sex With MenNatasha Martin, DPhil: A recent meta-analysis[2] looked at reinfection among people who inject drugs. It found that reinfection rates were actually relatively low. Among those with a history of injecting-drug use, reinfection with HCV after successful treatment was about 2 per 100 person-years. Among those who continued drug use after HCV treatment, reinfection rates were slightly higher, about 6 per 100 person-years. If you compare that with the primary incidence of HCV infection among people who inject drugs, that rate is actually quite low. The primary incidence is between 6 and 30 per 100 person-years. This indicates that reinfection rates are lower among those who have been treated. I would caution that there haven't been many studies. Only a few studies were included in the meta-analysis. The sample sizes were small and these studies were probably subject to substantial selection bias. We need more data on reinfection, but the evidence that we have says that reinfection rates are relatively low in this population.

Thomas C.S. Martin, MD: My work has been based more on HCV in HIV-infected men who have sex with men (MSM). The HCV epidemic is in its infancy in this population compared with people who inject drugs. Even fewer studies are available. From the few studies that we have, we know that reinfection is significant. In Amsterdam they found a very high reinfection rate -- about 15 per 100 person-years.[3] In London, where we have replicated this study, we found a rate of reinfection following HCV treatment of about 9 per 100 person-years.[4] Given the small numbers that are involved, these estimates have wide error bars. To put this in context the way that Natasha did, that would be approximately 5-10 times the baseline incidence rate of HCV among HIV-infected MSM. These people don't inject drugs; this is sexually transmitted HCV.

Dr Young: Clearly, HCV reinfection is happening, and I'm hearing that there are potential differences in different populations -- different risk factors or risk groups.

Dr. Natasha Martin: That is true. The risk for reinfection is often used to justify not providing treatment or a reluctance to provide treatment to drug injectors, but the data don't support that theory. Right now, it's unclear how these reinfection rates will affect treatment as prevention initiatives.

Dr. Thomas Martin: It's certainly in its infancy. People are treating HCV without guidance about how to manage reinfections, or about the impact of reinfections on factors such as cost-effectiveness and on overall HCV prevalence. That's where we are with MSM.

Does Better Treatment Encourage Risky Behavior?Dr. Young: We also talked about the impact of having direct-acting agents to treat HCV. In the HIV care arena, something we are very interested in is pre-exposure prophylaxis. One point of discussion about why we shouldn't implement pre-exposure prophylaxis for HCV is the idea that access to better-tolerated medicines will encourage people to be more risky or will encourage disinhibition of safe practices. Do you think that is going to be an issue here?

Dr. Thomas Martin: I would draw a parallel with the introduction of highly active antiretroviral therapy (HAART) during the HIV epidemic. A study in San Francisco[5] showed an increase in high-risk behavior with the introduction of effective treatment for HIV. People are rightly worried that in hepatitis C we will see an increase in risk behavior. If the treatment is just pills for 12 weeks, then I think we would see a change.

Dr. Natasha Martin: It's not clear among people who inject drugs, mainly because we don't have a lot of evidence. The evidence that we have indicates that just engaging with healthcare and going through the treatment process often has very positive outcomes among injectors, as far as reduction in risk behavior and increasing access to healthcare after treatment. It remains to be seen, because the new drugs are easier and they are better tolerated. More people will be willing to undergo treatment. We will see people go through treatment who we don't see currently. It will be interesting to see what happens with them as far as reinfection. The evidence that we have shows that going through treatment has very positive benefits in this population.

Hepatitis C Treatment Often More Cost-EffectiveDr. Young: Natasha, you raised a very interesting point in your presentation, that the treatment of HCV in people who are injection-drug users is actually more effective than treating the non-drug injectors. Could you expand on that?

Dr. Natasha Martin: That was based on some work we did that looked at the cost-effectiveness of the treatment of injectors.[6] In our analysis, we included the risk for reinfection, which you would expect reduces the cost-effectiveness of treatment of injectors. We also included a potential prevention benefit of treating those who have this ongoing infection risk. We compared that with treatment of those who had no risk for reinfection, but also no prevention benefit. It turns out that across the board, treatment of injectors was cost-effective. This was a United Kingdom analysis, and we looked at a variety of prevalence settings. Even in high-prevalence settings (60% chronic prevalence), the treatment of injectors would still be considered cost-effective. We also compared that with treatment of non-injectors. We found that in most settings, it was more cost-effective to treat injectors because of this additional substantial prevention benefit. The idea that treatment of injectors could be less cost-effective because of the risk for reinfection doesn't really hold true when you include this prevention benefit.

Dr Young: That is fascinating, because it runs counter to our intuition about who should be treated. Tom, as an academic clinical fellow, what should our clinical colleagues take away from this conversation?

Dr. Thomas Martin: The treatment is certainly effective for people who are actively injecting drugs. That was part of the ground shift that Natasha has been trying to achieve by saying that people who inject drugs can complete HCV treatment and remain clear of infection after they finish. We are trying to change the mindset of clinicians. That is probably the most important thing to take away, along with the fact that you will be having a larger population benefit.

It's going to be very interesting to see the translation to the MSM population as well. As Natasha said, if people remain at risk for transmission, you derive a greater population benefit. Many of the reinfections we see are in people aged 40-50 years. These are the people who remain at risk. Any treatment that has prevention benefit is likely to be quite significant in that population.

Dr Young: Thank you both. This has been a wonderful conversation. Thanks for making the journey across the pond to our conference here in New York. For the International Association of Providers of AIDS Care in New York City, I'm Dr. Benjamin Young.

Gilead Sciences' GILD +3.37% $1,000-a-day hepatitis C drug, Sovaldi, could hurt the bottom lines of insurance companies, according to an analysis conducted by Leerink, the investment bank.

Sovaldi is having one of the most successful drug launches ever, and could generate $1.5 billion in its first quarter on the market. A week ago, a  group of Democrats in the U.S. House of Representatives including longtime drug industry gadfly Henry Waxman wrote a stern letter to Gilead asking it to explain the high cost of the drug. This led Ana Gupte, who covers managed care for Leerink, to take a look at the effect to the expensive new drug on companies she covers. She found that for some companies treating patients with Sovaldi could hurt earnings per share by as much as 10%.

 

“If all the currently 9% eligible for Sovaldi were to receive the drug,” Gupte writes, “the price tag could be as much as $27B with over $8B in fully insured Managed Care. The major brunt is being experienced by Medicaid, Commercial and the Dual Eligibles with significant potential consumption by the newly insured with ObamaCare.”

The managed care companies Gupte looked at: CalifornaMolina Healthcare (MOH) , a California-based provider of Medicare services and, more recently Affordable Care Act plans; Healthnet (HNC), another California managed care player; Centene (CNT), a big managed care firm based in St. Louis; WellCare Health Plans (WCG); Wellcare Health Plans (WCG) in Tampa, FL; Universal America Corp. of White Plains, N.Y.; and insurance giants Wellpoint, Aetna AET +1.17%, UnitedHealth Group UNH +0.45%, and Cigna CI +5.44%.

From Leerink Analyst Ana Gupte: How insurers are affected by the launch of Gilead’s Sovaldi.

Something  Gupte doesn’t mention, but that I think is striking, is that these are very much the same companies that are involved in the rollout of the Affordable Care Act, and that greater involvement in the ObamaCare expansion, both through the expansion of Medicare and participation in the exchanges, may make things harder for companies when it comes to Sovaldi costs. That may provide a motivation for the government to look for ways to curb Sovaldi’s growth; it certainly provides a motivation for these companies to try to minimize the amount they pay for this new hepatitis C drug.

There’s a strong argument, from the perspective of the larger health care system, that Sovaldi’s price is fair. According to Mark Schoenebaum at ISI Group, it costs more per pill than Vertex’s Incivek, but is used for less time and is nearly twice as likely to result in patients being cured of the hepatitis C virus, which can cause liver failure. But in cases where a new, effective drug is launched, insurers are always going to worry about patients coming out of the woodwork. The classic example is heartburn, which was treated far less often before AstraZeneca launched Prilosec, which was very effective and became the best-selling drug in the world. With hepatitis C, these worries are increased because Gilead is looking to launch an all-oral pill containing Sovaldi which would replace the injections currently given to treat the virus, which have unpleasant side effects.

Gupte quotes the chief executive of Molina Healthcare, Mario J. Molina, saying that it may not make sense to rush to treat hepatitis C patients. “If you’ve got a patient who is advanced and has liver disease and is about to get a liver transplant, it makes sense to give treatment,” Molina says. “…[W]hat do we do about everybody else? If everyone in the U.S. with hepatitis C were treated with Sovaldi at its list price, it would cost $227 billion compared with the estimated $260 billion spent a year in the country for all drugs.”

One possibility is that the plans will seek to have hepatitis C treatment “carved out” of their plans — that they won’t cover it. Another big question is what will happen with competing drugs. AbbVie and Enanta have a regimen that requires many more pills, but seems to also be effective. Merck seems on track to launch an all-oral combo, too. Could there be competition on price? To biotechnology investors, that’s a key question, because one of the things drug companies have going for them is an amazing amount of pricing power. If drug prices drop, that’s bad for biotech and pharma.

Update: How did Waxman wind up going after Gilead? It turns out it’s a previously scheduled meeting. Get the full story from Drew Armstrong at Bloomberg via the story “How the Gilead letter from Waxman happened” on Storify.   https://storify.com/ArmstrongDrew/how-the-gilead-letter-from-waxman-happened

http://www.forbes.com/sites/matthewherper/2014/03/31/push-comes-to-shove-gileads-1000-pill-could-hurt-insurer-earnings/