Which Is Worse, Hepatitis B or Hepatitis C?

Chronic hepatitis B and chronic hepatitis C, while caused by different viruses are clinically indistinguishable. Both affect the liver and both are potentially fatal.  Over years or decades, chronic HBV and HCV infection can progress to severe liver diseases including cirrhosis, liver cancer, and ultimately end-stage liver failure.

However, until now, few head-to-head comparisons of clinical outcomes have been attempted.

So, we were really interested to read a new study published in the Journal of Clinical Infectious Diseases.  This study is the first in which the effects of hepatitis B and hepatitis C virus infections were compared in a relatively homogeneous population.

Researchers from Johns Hopkins, led by Oluwaseun Falade-Nwulia, studied almost 7,000 American men included in the large Multicenter AIDS Cohort Study (MACS) prospective database of men who have sex with men.

Approximately 5% of participants entered the study with each type of chronic hepatitis.  At the end of an 8 year follow-up, all-cause mortality was similar in both groups, but liver-related mortality was significantly higher for those with chronic hepatitis B infections. This finding held true for both HIV-negative and HIV-positive participants, including those who were severely immune-compromised.

Excluding the few men in the study who underwent treatment for hepatitis C, infection did not change the pattern. However, liver-related deaths among participants who were co-infected with hepatitis B and HIV and who were enrolled after 2002 were markedly lower than among those who were enrolled earlier, possibly reflecting use of newer antiviral drugs that are active against both HIV and hepatitis B virus.

These results are worth noting for a number of reasons.  First, they underscore the need for expansion of HBV screening and vaccination to protect against HBV infection. Second, they suggest individuals co-infected with HIV/HBV should be treated with dually active drugs.

And lastly, despite the recent surge of public health advertisements that have brought hepatitis C screening and treatment into the public eye, clinicians should remember that hepatitis B is still out there, and that effective oral treatment can save lives.

The biggest-selling drug in 2018 will be…

EvaluatePharma, a UK based company specializing in pharma and biotech analysis has been gazing long and hard into its crystal ball.

Having scrutinized the world’s leading 3,500 pharmaceutical and biotech companies they have come up with a list of what, they believe, will be the top 10 selling drugs in 2018.

1. Januvia       (diabetes) – $9.7 billion
2. Humira        (arthritis) – $8.2 billion
3. Avastin        (cancer) – $7.5 billion
4. Enbrel          (arthritis)  – $7.2 billon
5. Revlimid     (myelodysplastic syndrome) – $6.75 billion
6. Prevnar 13  (pneumococcal vaccine) – $6.72 billion
7. Rituxan         (cancer) – $6.3 billion
8. Lantus           (diabetes) – $5.9 billion
9. Remicade     (arthritis) – $5.8 billion
10. Advair            (COPD)  – $5.7 billion

Surprised?  No conventional molecules, no cholesterol lowering agents, no blood pressure meds and not a single new drug among the top ten.  However, they predict the #11 best seller will be GS-7977 – the much anticipated oral hepatitis C drug from Gilead Sciences .

Not so surprising, given the obesity epidemic sweeping the western world that 2 of the front runners are diabetes drugs. Likewise, given the globally aging population – 3 are for arthritis.

#5 may be a surprise to many. Few people had ever heard of myelodysplastic syndrome before ABC news anchor Robin Roberts announced last week that she has the disease.  Still, it’s predicted number 5 status doesn’t mean that an epidemic is expected – it’s still relatively rare with only 10,000 or so new cases detected each year. Its lofty status on the list is more to do with the price. It costs a staggering $10,000 or so for a 28 day supply of the pills.

Other predictions from the EvaluatePharma World Preview 2018 report:

• Worldwide prescription drug sales are forecast to total $885bn in 2018 an increase of 3.1% from 2011
• Over $290bn of pharmaceutical sales are at risk from patent expirations between now and 2018
• Pfizer was the top company for prescription drug sales in 2011, but  Novartis will top the list by 2018
• Global pharmaceutical R&D spend forecast will grow by 1.5% per year to $149bn in 2018
• Anti-coagulants (blood thinners) are set to record highest growth of major therapy categories to 2018

Interesting stuff. But the problem with such long term predictive models is that they are but a snapshot  trying to project out six years.

In reality, life is a movie, with a frequently changing plot. For example if J&J’s canagliflozin can reduce obesity and improve blood sugar levels better than Januvia then the projected No. 1 ranking is suspect, at best.

Breaking Cancer News– 122 years later!

On December 3, 1890 William Russell, a pathologist in the School of Medicine at the Royal Infirmary in Edinburgh, gave an address to the Pathological Society of London.  In it he outlined his findings of “a characteristic organism of cancer” that he had observed microscopically in all forms of cancer that he examined, as well as in certain cases of tuberculosis, syphilis and skin infection.

On May 8, 2012, Catherine de Martel and Martyn Plummer from the International Agency for Research on Cancer in France announced: “Infections with certain viruses, bacteria, and parasites are one of the biggest and preventable causes of cancer worldwide.”

In case you haven’t already done the math, that means it’s taken 122 years for someone to take notice.

A hundred and twenty two years ago!  That’s the year Eiffel Tower was completed, it’s around the time that  serial killer Jack the Ripper was terrorizing London, the same year Thomas Edison used electric Christmas lights for the first time and the year Vincent Van Gogh, the Dutch painter, committed suicide.

How, you might ask, have scientists put men on the moon, developed the internet, flying cars and metal-free underwear bombs, but yet remain so ignorant about cancer and its origin?

How can the infectious causes of tuberculosis, leprosy, syphilis, smallpox, polio, malaria, and other viral and bacterial and parasitic diseases be so well understood, but the cause of cancer be unknown?

The fact that all cancers could conceivably be caused by an infectious agent now seems a distinct possibility. That, until now,  this has been overlooked, ignored, or unrecognized by twentieth century doctors is simply incredible.

According to de Martel and Plummer, one in six cancers, accounting for around two million cases a year, are caused by preventable infections. They claim “application of existing public-health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on future burden of cancer worldwide.”

The percentage of cancers related to infection is about three times higher in developing than in developed countries. For example the fraction of infection-related cancers is around 3.3%in Australia and New Zealand to 32.7% in sub-Saharan Africa.

Many infection-related cancers are preventable, particularly those associated with human papillomaviruses (HPV), Helicobacter pylori (H. pylori), hepatitis B (HBV) and C viruses (HCV).

Of these infection-related cancers, cervical cancer accounts for around half of the cancer in women. In men, liver and gastric cancers accounted for more than 80%.

Dr. de Martel says: “Although cancer is considered a major non-communicable disease, a sizable proportion of its causation is infectious and simple non-communicable disease paradigms will not be sufficient.”

Clearly we need to start making up for 122 years of lost time and directing further research and treatment efforts into these preventable causes of cancer.  Since vaccines for HPV and HBV are available, and increasing their availability, and lowering the cost should be a priority for governments and health systems around the world.

Cure for hepatitis C gets closer

About 170 million people worldwide are estimated to have been infected with Hepatitis C.

Among them, many celebrities including: actor  Larry Hagman; Rolling Stone Keith Richards; American Idol judge Steven Tyler; Baywatch babe Pamela Anderson; stuntman Evel Knievel and “Dr Death” Jack Kevorkian.

Currently there is no cure for this bloodborne, liver destroying virus and until recently there has been no specific treatment. Although interferon injections have been used, the  flu-like symptoms and other side effects often lead patients to discontinue or delay treatment.

However, in the last two years, two new injectable treatments were approved for use and clinical trials of oral medicines demonstrate promising results.

Earlier this month Abbott Laboratories released impressive data from a small mid-stage trial combining its experimental protease inhibitor ABT-450 boosted by the antiviral drug ritonavir, along with a polymerase inhibitor and ribavirin. The combination achieved a 95% cure rate in one arm of the study.

Separately, Gilead reported results from the Electron study, showing that of 88% of the 25 patients who completed 12 weeks of treatment with GS-7977 and ribavirin, had undetectable levels of virus four weeks after completion of treatment.

And last Thursday, at a liver disease meeting in Europe, researchers released interim data showing that a combination regimen of  GS-7977 from Gilead Sciences Inc and daclatasvir  from Bristol-Myers Squibb Co led to a 100% response rate in previously untreated patients with the most common form of hepatitis C.

GS-7977 is a nucleotide polymerase inhibitor. Daclatasvir  is from a new class of drugs known as NS5A inhibitors. Both are designed to block enzymes essential to replication of the hepatitis C virus.

All 44 of the patients who had the most common and difficult to treat type of hepatitis C (Genotype 1)  had undetectable levels of the virus in their blood four weeks after completing treatment, while 40 out of 44 patients with Genotypes 2 or 3 had undetectable levels of virus at four weeks following treatment -a 91% response rate.

The experimental drugs were considered to be well tolerated with the most frequent side effects being fatigue, headache and nausea. Full results from the trial are expected later this year.

Despite these promising results the 2 companies have decided not to pursue a collaboration.  Gilead is now commencing a trial of GS- 7977 in combination with its own experimental NS5A inhibitor, while Bristol-Myers is testing its drug daclatasvir with a compound similar to GS-7977.

The race for a cure seems to be well and truly on…and whoever comes first the real winners will be the people already infected.

Mysterious Hep A Immune Response Has Implications For Hep C Research

Hepatitis C virus

SRxA’s Word on Health was interested to read a new animal study which sheds new light on the nature of the body’s immune response to hepatitis C virus (HCV) and hepatitis A virus (HAV).

By comparing these two viruses that infect the liver, one that is always cleared by the immune system – HAV, and one that frequently evades the immune response – HCV, the team hoped to unravel the mystery of how HCV causes lifelong persistent infections.

Understanding how the immune system responds to HCV is very important because more than 200 million people worldwide and 3.2 million people in the U.S. are chronically infected and at risk for progression to liver cirrhosis and liver cancer. Hepatitis C associated liver disease is the most common indication for liver transplantation, while liver cancer due to HCV infection is now the fastest growing cause of cancer death in the U.S.

“Hepatitis viruses have co-evolved with humans over a very long period of time and they are good at evading the immune system, but nobody understands how hepatitis C becomes a chronic infection,” commented study co-author Stanley M. Lemon, M.D., of UNC.

Hepatitis A virus

Surprisingly, the researchers found that HAV, a relatively benign virus that causes nausea, vomiting and lethargy, and has no chronic state was more adept at evading the innate immune response than HCV.  Examination of the adaptive immune system found that the T cell response to HAV was unique as well. Although the scientists expected the immune response to kill all HAV infected cells in a short time frame, instead they found that the genome of the virus could be detected in the liver for up to one year, long after symptoms of the disease were resolved.

The new study points out the critical need for more information about how the immune system reacts to HCV. It also reinforces the importance of animal research in this instance as the chimpanzee is the only animal model susceptible to HCV infection.

Such research is vital.

Unlike hepatitis A and B for which vaccines are widely available there is no hepatitis C vaccine. There are three basic reasons for this:

• As mentioned above, there is no effective small animal model or cell culture system. This makes vaccine development very challenging because researchers can’t see how the virus really works in a natural environment.
• HCV has different genotypes.  Since hepatitis C has at least six genotypes, several different vaccines would be needed to protect against each genotype.
• HCV mutates very easily. This means that some of its genetic code can change a little bit when it replicates itself. The result is a virus that keeps its genotype, but is different enough to confuse a vaccine.

Come to think of it,  HAV studies aren’t all that easy either. Almost 20 years ago I was peripherally involved with an HAV infectivity study. A biological product I was working with at the time had been implicated in the transmission of  HAV infection.  The suspect product was injected into chimps to see if they would develop the disease.  A second group of chimps housed in cages across the room were not injected, and served as controls. Unfortunately the study had to be terminated early because the test animals started throwing feces at the control group.

Not the outcome we were looking for, but a valuable exercise in the “how not’s” of clinical research!