Hepatitis C and Kidney Disease

This evening from 6-8 PM at the Mass General was a nice interdisciplinary symposium regarding Hepatitis C with a particular focus on kidney disease. The session was organized by Dr. Meghan Sise, a MGH nephrologist. The attendees included nephrologists, hepatologists, ID doctors, and surgeons. A few highlights:

  • Jai Radhakrishnan from Columbia University explained that HCV is most often associated with immune-mediated cryoglobulinemic vasculitis and MPGN
  • Raymond Chung from MGH spoke about the rapidly changing landscape of HCV drugs. He went over some of the most important clinical trials (COSMOS, ION-2, SAPPHIRE, TURQUOISE-II, ALLY-3).  The bottom line is HCV medications are continuing to change quickly and we should be consulting the HCV Guidelines website frequently.
  • Alysse Wurcel, my medical school classmate, who is now an ID doctor at Tufts, spoke about cotreatment of HIV/HCV. She made a number of important points, but one that I particularly agreed with was the importance of intensive follow-up with these patients and open discourse about drug and alcohol use. Substance use can be a barrier to achieving an SVR and can get in the way of HIV viral suppression, and the physician-patient relationship is key.
  • Meghan Sise talked about cryoglobulinemic glomerulonephritis in the context of HCV
  • Craig Gordon, a nephrologist from BMC, spoke about HCV treatment and ESRD
  • I’ve blogged previously about Hepatitis C/ HIV coinfection and the general messages remain the same. These treatments are potentially life saving if they can lead to SVR and prevent the sequellae of cirrhosis but they remain very expensive. This field of Hepatitis C is rapidly changing and will be getting only more complicated in the future. Just remembering the names of these medications is a challenge. It’s making learning Korean look easy!
Alysse Wurcel's conclusions

Alysse Wurcel’s “take home points” slide

On Buprenorphine…

Today’s lunchtime conference at the Brigham was given by Dr. Mark Eisenberg, a physician at MGH-Charlestown since 1985. I was only able to stay for part of the discussion because I had a conflicting meeting but even a few minutes of listening to him was worthwhile. He has taken care of many people who use drugs over his career and told us some lessons learned from years of prescribing buprenorphine. Unlike most teaching conferences, he sat at the table (no powerpoint slides!) and had a conversation about his experiences.

Dr. Eisenberg reminded us of the history of HIV primary care, which began in the 1980s. HIV/AIDS in 1985 was an epidemic among people who were highly stigmatized, primarily gay men, Haitians, and intravenous drug users. Almost all were dying and doctors had no effective treatments to offer. Dr. Eisenberg told us he went to many wakes and funerals and had to comfort family members who asked him, “why did my son die of this illness?” Blame and fear were everywhere, with people saying that gay men choose their behaviors and were knowlingly putting themselves at risk. But everything changed in 1996 with the advent of ART. “It really was the ‘Lazarus effect,'” he said, as AIDS patients were rising from dead and getting their lives back.

Similarly, heroin addiction has always been a highly stigmatized illness. Methadone maintenance had been an option but when buprenorphine became available in 2003 that changed the landscape for people who used drugs because they would no longer have to go to a methadone clinic every day to pick up their medications. Dr. Eisenberg took an 8 hour training course on how to prescribe buprenorphine and soon had a number of patients receiving the medication. From time to time, he has seen the ‘Lazarus effect’ with this medication as well. For many patients who are able to get their opiate addiction under control, the drug is “truly miraculous.”

A few other points I found powerful:

  • Stigma is widespread against people who use drugs. He suggests we write “opiate use disorder,” not “substance abuse/abuser” in the medical chart. The word “abuse” has strong negative connotations.
  • When a patient with leukemia relapses, we don’t say that the patient “Failed her treatment.” So don’t blame a person who uses drugs for “failing treatment,” either.
  • It’s not easy to prescribe buprenorphine. Many patients aren’t committed to sobriety. Their family members may make them attend the clinic, for example. There is certainly some scamming going on and clinicians deal with this different ways. A committed, multidisciplinary clinical team is needed to help these patients. 

Drug use is widespread, throughout Boston, the United States, and the world. We really do need to recognize the importance of helping our patients control their addictions.

President Obama in Alaska

Most of my blog entries are focused on infectious diseases such as HIV and tuberculosis because those are the fields I know best. But from time to time an important non-medical issue comes up that I feel compelled to write about. Today is one of those days.

100 days before the big UN climate talks in Paris, President Barack Obama is traveling to Alaska to examine the effects of climate change. (As background, if you aren’t well versed on drilling in the Arctic, I suggest watching Obama’s Youtube video and glancing at the following New York Times articles (1, 2, 3, 4), before continuing on to my blog entry).

President Obama argues that his administration has “worked to make sure that our oil exploration conducted under these leases is done at the highest standards possible” and “safety has been and will continue to be” his top priority. Meanwhile, presidential candidate Hillary Clinton came to the opposite conclusion. On August 18th, she tweeted, “The Arctic is a unique treasure. Given what we know, it’s not worth the risk of drilling. -H.”

How to reconcile these opposite viewpoints? It’s politics. Barack Obama is winding down his last term while Hillary Clinton is engaged in an unexpectedly difficult primary campaign, pushed from the left by Bernie Sanders. While it appears that Obama’s stance may be driven by industry interests and Clinton’s stance may be due to pressure from climate activists, I think it’s more complicated than that. The multinational oil companies have a target of reserves to discover each year. Preventing them from exploring for new oil is another way of putting a limit on how much carbon they can unearth. Much of this issue has to do with the price of crude. The lower the price, the less oil that will be extracted (because it’s less profitable). You can lower the price by increasing supply (which doesn’t stop climate change), reducing demand (by developing alternative energy sources like wind or solar), or implementing a carbon tax (this remains a political nonstarter).

When analyzing Obama’s visit to the Arctic, we mustn’t forget the complex history of drilling, for example the Exxon Valdez and Deepwater Horizon spills and subsequent political fallout. No matter how much politicians and industry reassure us that drilling is “safe,” history suggests otherwise. Enforcement and regulation is the issue. If oil companies aren’t forced to do their work safely by threat of large fines from the government, they won’t, because their purpose is to maximize profits for shareholders. And as the climate activists have made clear, a major oil spill off the north slope like what happened in the Gulf of Mexico with the Deepwater Horizon could be catastrophic, permanently altering the environment. The Arctic is the harshest climate on earth. Oil platforms, pipelines, and slogans like “safety is our top priority” aren’t necessarily going to survive against the Arctic sea ice.

Meanwhile, the geopolitics in the Arctic are also complex. Steven Lee Myers implies that we might be headed towards a second “Cold War” with Russia, the battlefield being the extraction of resources from the Arctic (perhaps this should be called a “Warm War”).

So what should be done to reduce the extraction of oil? It comes down to combustion. We must each burn dramatically less fossil fuels. To do this, there needs to be a change in the debate about global warming. Traditional media and social media can play a role, but the magnitude of this problem is immense. Climate change will require a grassroots social movement like we’ve never seen before, led by ordinary citizens. Where are the doctors and nurses and public health experts on this issue (myself included)? Why haven’t I been attending climate rallies? Too busy? The health of the planet is intimately connected to the health of its inhabitants– our patients.

President Obama has done lots of good things in the oval office but unfortunately he has failed to live up to his 2008 campaign slogans, “Change we can believe in” and “Yes we can.” The grassroots effort to get Obama elected was certainly inspiring. But after the victory, we, his constituents, became complacent. We thought that electing Obama was all it would take to make long-lasting change in America. Our attention spans were short and we didn’t realize that change comes from an “interaction between grassroots mobilization and elected leaders,” to quote my friend, the sociologist Adam Reich.

But climate change is a growing emergency and it’s time for an organized movement to counter it, and today is the day to begin. Barack Obama is still our President and is in office for another 16 months. We can influence his actions. As Franklin Delano Roosevelt said, when a progressive group brought him an idea:  “I agree with you, I want to do it, now make me do it.”

Please remember my disclaimer. I’ve never been to Alaska. I am a practicing physician, not a geologist or economist, so I can’t pretend to understand climate change in depth. But I do know that we must stop global warming if we want our children and grandchildren to inhabit a livable planet. What do you think?

As Franklin Delano Roosevelt said, when a progressive group brought him an idea:

As Franklin Delano Roosevelt said, when a progressive group brought him an idea: “I agree with you, I want to do it, now make me do it.”

This post is dedicated to the late Dr. Paul Epstein, a physician who also worked in Mozambique early in his career (1977-1980) and was passionate about protecting the environment. His powerful book, Changing Planet, Changing Health, written with Dan Ferber, was a major influence on my own thinking about climate and health. I first read their book while working in northern Zambia. The Zambia-DRC border is home to a number of copper mines and significant pollution. I recall the smell of burning metal in the air while reading this book in my hotel room at night. Also, thanks to several of my colleagues who provided major input on earlier versions of this blog post. 

A tale of two global emergencies…

Today I want to bring attention to an excellent article that my friend and collaborator Dr. Ruvandhi Nathavitharana and her coauthor Jon Friedland have published, entitled, “A tale of two global emergencies: tuberculosis control efforts can learn from the Ebola outbreak.” In it, she describes the neglect of infection control and resulting health care worker infections from Ebola and TB. Ruvandhi calls for “sustained political commitment and community engagement” and I completely agree. What can/should be done? I’d put it simply, citing Dr. Mark Rosenberg: “Real collaboration,” which is truly what it takes for global health to succeed. We must strive to develop long term collaborative (not exploitative) relationships. That’s much easier said than done, given how global health is financed and delivered in the real world. But we must try. I suggest that anyone considering working internationally read Ruvandhi’s article and Mark’s book and reflect on their messages. Your thoughts?

Bullseye

It’s summertime and people are hiking and camping throughout New England. Today’s teaching conference at MGH/Brigham was given by Dr. Howard Heller regarding tick-borne illnesses. He focused on Lyme Disease because it is the most common tick-borne illness in our region. Howard emphasized that while Lyme is hyperendmic in coastal Massachusetts (Cape Cod, Martha’s Vineyard, Nantucket), the Berkshires in Western Mass are also hyperendemic. And Lyme is actually found throughout the region, and patients can get infected even in well-off enclaves like Cambridge and Newton. A few other points he made:

  • The manifestations of Lyme are protean. During tick season, be sure to consider Lyme even without a clear tick exposure when patients present with a febrile illness, rash of any sort, meningitis, Bell’s Palsy, etc.
  • Ticks are tiny and are often missed even when people are doing those tick checks. If there’s a rash in an area of the body where ticks are likely to come into contact (popliteal fossa, etc), consider Lyme, even if the rash isn’t a classic bullseye (erythema migrans). Be sure to undress the patient and do a complete dermatologic exam.
  • Diagnosis of Lyme is made by serology and should be sent to a reliable laboratory
  • Follow the IDSA guidelines (and American Academy of Neurology guidelines for CNS Lyme)
  • Be sure to test for anaplasma/babesia, as those diseases frequently co-exist with Lyme and require different treatment.

The main question I have coming out of this lecture is about the epidemiology of Lyme and the other tick-borne diseases. It is believed that changes in land management practices have contributed to the rise in Lyme. But what can be done to reduce the incidence of all of these tick-borne illnesses?

800px-Adult_deer_tick

This little tick looks so friendly, right? Actually, it can pack a nasty punch

On Clostridium Difficile

Get out your blenders. Today I attended a lunchtime lecture given by Dr. Jessica Allegretti, a Brigham gastroenterologist who specializes in recurrent Clostridium difficile and fecal microbiota transplants (FMT). I don’t think I need to review the burden of disease caused by C diff, as most readers of my blog probably are aware that C diff is a major problem. The “hypervirulent strain” (NAP1/BI/027) of C diff which causes severe pseudomembranous colitis is also concerning (although NAP1 has been on the decline since 2007).  Recurrences of C diff are common and the medications we use most often, metronidazole and vancomycin, are frequently ineffective. In addition, fidaxomicin, a second line medication, is very expensive. In her lecture, Dr. Allegretti commented that “unnecessary antibiotics are rampant” in the community causing recurrent C diff. As a result, she is busy doing traditional FMT (hence the blender comment). She is also performing transplants via frozen capsules. Her frozen capsules are compounded at MIT and are given 2 days in a row in the office (30 capsules each day). Dr. Allegretti reports that the majority of patients have a rapid reversal of symptoms within 24 hours and are cured. That’s good to hear, but I think it’s a sad state of affairs when C diff is common and FMT is becoming more and more necessary. There is a lack of motivation from clinicians, patients, and the health system to reduce the unnecessary use of antibiotics. As a result, people, young and old keep getting sick from C diff. Hopefully we aren’t approaching the “antibiotic winter” described by Dr. Martin Blaser.

Immunogenicity of a Cholera Vaccine in Haitian Adults with HIV

This evening, I enjoyed catching up with a medical school friend who works extensively in Haiti. Upon returning home I found an issue of the Journal of Infectious Diseases in my mailbox. Opening it up, I discovered an article written by several of my colleagues from Mass General/ Brigham about the oral cholera vaccine in adults with HIV infection in Haiti. Caveats regarding this blog post: I don’t  claim to know much about cholera and I haven’t spoken with any of my Mass General/Brigham colleagues regarding this study.

This study is important because cholera often occurs in parts of the world where there is a high burden of HIV. For example, in Beira, Mozambique (about an hour flight north from Maputo), there was cholera in 2005-2006 and a research paper suggested that HIV infection was associated with an increased risk for cholera. Thankfully there were no outbreaks of cholera in Mozambique when I worked/lived there (2011-2012), but it was always a consideration when a patient came into the hospital with profuse diarrhea. Even though more and more people with HIV are getting on lifesaving antiretroviral therapy in Mozambique and around the world, the burden of HIV remains enormous. Cholera transmission is ongoing in many of these settings so individuals with HIV remain at risk. Now, lets journey to Haiti.

Louise Ivers and colleagues studied Haitian individuals with HIV who had received the bivalent oral cholera vaccine BivWC which is marketed as “Shanchol.”  This is a killed whole-cell bacterial vaccine. Since the Haiti earthquake and subsequent cholera epidemic, the Haitian Ministry of Health has rolled out the BivWC vaccine in an attempt to reduce cholera transmission. In St. Marc, Haiti adults with HIV infection received the vaccine and their serum was shipped to Boston for immunological analysis. In this paper, the researchers studied 25 adults with HIV who received BivWC. The median CD4 count of these patients was 433. All but two were on ART and the two who were not on ART had CD4 counts above 500. The researchers found that adults with HIV had a decreased vibriocidal antibody response to the BivWC vaccine, especially for patients with the lowest CD4 counts. However, the majority of HIV-infected individuals still did have seroconversion to the vaccine.

Ivers and colleagues comment on the small sample size and the fact that vibriocidal antibodies are not likely to directly mediate protection from cholera, so their study does not definitively address the question of vaccine efficacy in HIV infected individuals. That makes sense. My main question for the researchers would be about the CD4 cell counts. In many parts of Sub-Saharan Africa where cholera transmission occurs and there is a high prevalence of HIV (I am thinking of Beira, Mozambique for example), there remain many people who are not on ART. People with AIDS are at high risk for opportunistic infections and diseases like cholera because of their advanced immunosuppression. Practically speaking, human resources are limited in such settings (overloaded clinics, lack of nurses, etc) but cholera transmission must be avoided at all costs. Is there enough evidence to roll out the BivWC vaccine widely in such settings? The authors comment that additional doses of vaccine might need to be given to people with low CD4 counts. What kind of studies would be needed to investigate this question?

Thanks to the power of Twitter, Louise Ivers already wrote back. She said, “vaccine safe, and reasonable seroconversion in HIV but need bigger study w/ lower cd4 counts. Vaccine also in v short supply”

St. Marc, Haiti

St. Marc, Haiti