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October 2012 HCV Advocate

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In This Issue:

Advances in Liver Transplantation
Alan Franciscus, Editor-in-Chief

HCV Snapshots
Lucinda K. Porter, RN

HealthWise: - When HCV Treatment is Over
Lucinda K. Porter, RN


Type 2 Diabetes and Insulin Resistance in People with HCV Part 1
Liz Highleyman



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Advances in Liver Transplantation
—Alan Franciscus, Editor-in-Chief

Hepatitis C is the leading cause of liver transplants in the United States and accounts for over one-half of all transplants.  Since the hepatitis C virus is in the blood, reinfection almost always occurs and, for some, serious disease progression can occur very quickly.  The best case scenario would be another liver transplant, but given the shortage of available livers many people will, unfortunately, die.

The statistics for livers available to those who need a transplant are not very encouraging:  It is estimated that every year 17,000 people will need a liver transplant yet only 6,000 will receive one.  This is why it is so important that everyone promotes organ donation awareness.

Another strategy is to treat  HCV well before the liver becomes damaged.  As a last resort HCV treatment before a transplant might result in a cure and the newly transplanted liver would not become infected.  Two new studies are showing promise in addressing the problem  of universal re-infection.  The first study uses a monoclonal antibody to prevent re-infection.1  The second study addresses treating HCV after the transplant with a direct acting antiviral (DAA) medication in combination with pegylated interferon (PEG) and ribavirin (RBV).2  The studies are both proof-of-concept studies that will hopefully lead to even more studies to establish a standard of care for treatment of liver transplant patients. 

Another strategy to increase the number of livers available for transplantation is with live liver donors.  In this type of transplant a person is matched up to donate a portion of their liver with a potential transplant patient (most times relatives).  This has been shown to save lives, but it is not without controversy since there are legal, moral and monetary considerations that should be carefully addressed.  Although live liver donor transplants (LLDT) have been shown to be successful, only 200 to 300 LLDT’s are performed every year in the United States.  This is most likely due to news of donor deaths, although this seldom occurs. 

This article will also report on a study from Japan on the 1, 5 and 10 year survival rates from LLDT.3  The article from  Japan is not HCV specific but it does give us information about the safety of such a procedure that can somewhat translate to HCV LLDT transplant patients. 

Monoclonal Antibody
The first study – a report about a monoclonal antibody (HCV1) developed by MassBiologics1 – used post-transplant provided proof of concept that the use of HCV1 can prevent HCV re-infection of the liver in chimpanzees.  The study was designed to mimic the setting of liver transplantation in humans.   The study was reported by MassBiologics of the University of Massachusetts Medical School (UMMS), the National Institutes of Health (NIH), Merck Research Laboratories and was conducted by Texas Biomed’s Southwest National Primate Research Center. 

HCV1 works by preventing the hepatitis C virus from entering liver cells by binding to the outside of a liver cell.  This was an important step in the development of an effective prevention of re-infection of the liver by the hepatitis C virus.  This is especially important in a transplant setting since almost all of the patients who are HCV positive pre-transplant will develop HCV infection post-transplant.  The next step would be to use HCV1 in those with HCV who are receiving a liver transplant and—as pointed out by one of the researchers—combine it with HCV medications such as a DAA to find out if it would be even more effective in preventing re-infection of the liver.

DAA Treatment
HCV treatment post-transplant is difficult for a variety of reasons including the drug-drug interactions between the HCV medications and the anti-rejection drugs (used to lower immune response, but which also increase HCV replication), lower efficacy, and because the immune system (and body) is recuperating from major surgery.  Pegylated interferon and ribavirin is the current standard of care for treatment post-transplant, but efficacy is less than optimal and side effects can be debilitating especially for someone who has just received a transplant.  The first direct-acting antivirals developed for the treatment of hepatitis C—boceprevir and telaprevir—can not be used as HCV therapy post-transplant because of the drug-drug (DDI) interactions with organ anti-rejection drugs (cyclosporine and tacrolimus). 

“A Case Report of Successful Peginterferon, Ribavirin, and Daclatasvir Therapy for Recurrent Cholestatic hepatitis C following Retransplantation” by RJ Fontana and colleagues2 is the first to report a successful outcome post-transplant using a combination of medications including a DAA.  A 49 year old female (HCV genotype 1b) initially received a liver transplant, but soon developed severe liver damage that prompted treatment with PEG/RBV.  The patient initially responded to PEG/RBV, but the liver became so damaged that a second liver transplant was required and performed at 9 months post-transplant.   Due to the recurrence of HCV  and the resulting increase in damage to the liver after the second transplant, the patient was started on a combination of pegylated interferon (180 ug injected once-a-week), ribavirin (a pill taken twice a day (BID) – total-800 mg daily) and daclatasvir (a 20 mg pill taken once daily (QD)). Daclatasvir is an HCV NS5a inhibitor. 

Note:  The dose of ribavirin was lower than usually given, but is typical of post-transplant treatment.  The dose of daclatasvir was also lower because of the drug-drug interaction with cyclosporine.  Cyclosporine increases the level of daclatasvir in the bloodstream.  This means that people who received the 20 mg/day dose had the same drug levels in the blood as those who received the standard dose (60 mg/day).

After 3 weeks of triple therapy the patient became HCV RNA (viral load) negative and her biochemical markers improved.  HCV RNA remained negative during the entire 24 week treatment period with the triple combination and the additional 4-week treatment with PEG/RBV, but without daclatasvir.  Daclatasvir was well-tolerated by the patient.

This case study was important because it was the first to show that the triple combination of PEG/RBV and a DAA could cure HCV post-transplant.  Another important aspect of this case is that the patient was treated for a shorter treatment duration (28 vs. 48 weeks)—transplant patients have a tendency to have more side effects, drug-drug interactions, and reduced quality of life.  The addition of a DAA to PEG/RBV for post-transplant treatment means that there will be a shorter duration of treatment that will translate to less side effects, better quality of life and the big payoff—a higher cure rate in a group of people who have few options.  That all sounds like excellent news to me.1

LLDT Survival
A recently released study—”Outcomes After Living Donor Liver Transplantation for Acute Liver Failure in Japan:  Results of a Nationwide Survey,” by N Yamashiki and colleagues3—is helping us understand the short- and long-term survival of people who receive a live liver donor transplant.  The study included 206 acute liver failure Japanese patients who received an LLDT among whom HBV (61%) was the most common reason for acute liver failure followed by autoimmune hepatitis (14%), and drug allergy-induced hepatitis (14%).  The survival rate for 1 year after LLDT was 79%; 5 year survival was 74% and 10 year survival was 73%.  Patient age was found to be associated with short- and long-term mortality; and donor age affected long-term mortality; a difference in blood type affected short-term survival.  It was found that the type of liver disease that necessitated the transplant did not affect survival of the person who received the LLDT.

These studies are all good news for people who may be approaching a stage of liver disease that may require a liver transplant.  The rapid advance of drugs in development, medications to prevent re-infection of the liver after transplantation and the recommendations from the Centers for Disease Control and Prevention earlier this year will mean that there will be fewer HCV disease-related liver transplants in the future.  There is also something that we can all do—yes, even people with hepatitis C—that is to donate their organs.  Give the gift of life.

Organ Donation:
http://donatelife.net/understanding-donation/organ-donation/

 

Notes:
1. Morin TJ, Broering TJ, Leav BA, Blair BM, Rowley KJ, et al. (2012) Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees. PLoS Pathog 8(8): e1002895.doi:10.1371/
journal.ppat.1002895

2. Liver Transpl. 2012 Sep;18(9):1053-9. doi: 10.1002/lt.23482.

3. Liver Transplantation, Volume 18, Issue 9, pages 1069–1077, September 2012



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HCV Snapshots
—Lucinda K. Porter, RN

Article: Pegylated Interferon for Chronic Hepatitis C in Children Affects Growth and Body Composition: Results from the Pediatric Study of Hepatitis C (PEDS-C) Trial, by Jonas M, Balistreri W, Gonzalez-Peralta R, et al.
  Source: Hepatology; Volume 56, Issue 2, pages 523–531, August 2012

Enrolling children with chronic hepatitis C virus (HCV) infection, this prospective study examined the relationship between interferon and growth. There were 114 participants (55% male), with an average age of 11. Subjects were divided into three groups according to duration of treatment: 14 subjects in the 24 week group, 82 in the 48 week group, 11 in the 72 week group (7 participants who did not make it to week 24 were not followed).

Children experienced significant reductions in height, weight, and body mass index (BMI) during HCV therapy, despite no changes in physical activity or food intake. Children who were treated with peginterferon for 48 or 72 weeks had lower average height scores at the two-year follow-up point than when treatment began. These effects were generally reversible after stopping interferon, with the exception of the height-for-age scores.

The Bottom Line: HCV treatment for children is associated with reduced growth rate.

Editorial Comment: This study merely shows an association between interferon and growth, not a cause and effect. Children with HCV are a small portion of the HCV population, and studies of this age group are few. It would be interesting to see future follow-up data on this cohort.

Article: Myocardial Injury in Patients with Chronic Hepatitis C Infection, by Maruyama S, Koda, M, Oyake N, et al.
  Source: Journal of Hepatology; published online August 13, 2012

Responding to a recent HCV treatment clinical trial reporting that patients were prone to myocardial perfusion defects (impaired blood flow to the heart), Japanese researchers studied this further. Various cardiac tests were performed on 217 HCV patients who had no obvious symptoms or history of heart disease. Of these, 200 were treated with interferon-based therapy for 24 or 48 weeks, and were evaluated 2 weeks before, 2 weeks after and 6 months after therapy.

Of these, 9% had abnormal ECG’s prior to treatment and a measurement of blood flow indicated injury in 87%. However, those who had a sustained virologic response (SVR) to treatment had significant improvement. Responders who later relapsed also showed cardiac improvement but returned to baseline during follow-up. Non-responders had no improvement.

The Bottom Line: HCV is associated with cardiac abnormalities and treatment for HCV seems to significantly reduce this association. 

Editorial Comment: Last month, it was reported that patients with HCV have a higher risk of death from all causes, including cardiac. This study sheds more light on this issue, and, presumably, more information about HCV’s impact on health and mortality will be forthcoming.

Article: Curcumin Inhibits HCV Replication by Induction of Heme Oxygenase-1 And Suppression of AKT, by Chen MH, Lee MY, Chunag JJ, et al.
  Source: International Journal of Molecular Medicine Epub August 20, 2012

Curcumin is one of the components in turmeric, a spice used in Chinese medicine as well as in Indian cooking. This in vitro study (performed in a lab, not on humans) conducted by Chinese scientists, investigated the effect of curcumin on HCV. 

The Bottom Line: Curcumin inhibited HCV replication in the laboratory setting.

Editorial Comment: Lab studies are the beginning of the research process, so one can’t make sweeping judgments about curcumin’s ability to inhibit HCV replication based on this. However, this is a good start. Curcumin is known to have anti-inflammatory and antioxidant properties, and at high doses may have anti-cancer properties. It is delicious and is generally regarded as safe.

Article: Hepatitis B and C Virus Infection Among 1.2 Million Persons With Access to Care: Factors Associated With Testing and Infection Prevalence by Spradling P, Rupp L, Moorman L, et al.
  Source: Clinical Infectious Diseases Epub August 8, 2012

This observational study measured whether people in the private healthcare setting were screened for hepatitis B and C. From 2006-2008, data was collected from 1.25 million adults from four U.S. healthcare organizations. Results were compared to data from the National Health and Nutrition Examination Survey (NHANES).

These results were:

  • Less than half of those with abnormal alanine aminotransferase (ALT) levels were tested for HBV or HCV.

  • Of 866,886 persons without a previous HBV diagnosis, nearly 19% were tested; 1.4% tested HBV positive.

  • When tested, Asians were most likely than whites to have HBV.

  • Of 865,659 without a previous HCV diagnosis, nearly 13% were tested;5.5% tested HCV positive.

  • When tested, those aged 50–59 years were most likely to have HCV.

  • Using NHANES estimates, nearly one-half of HCV and one-fifth of HBV infections in this population were not identified.

The Bottom Line: Even with access to healthcare, people are not being adequately screened for HBV and HCV, even with the presence of elevated liver enzymes.

Editorial Comment: Although these results are tragic, this study took place prior to the new CDC recommendations to test all people born 1945 through 1965. I am curious to know how these results will be a few years from now.

 

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HEALTHWISE: When HCV Treatment is Over
—Lucinda K. Porter, RN

Triple-therapies using protease inhibitors to treat chronic hepatitis C virus (HCV) infection have been in use for over a year. Response rates are better than ever; some achieve these results with shorter lengths of treatment. Tempering this good news are downsides, including increased intensity of side effects, the potential for drug resistance, and a long list of medications that may potentially interact with the proteases.  

Last month I asked the HCV community for tips for patients who are undergoing antiviral therapy. As patients reach the finish line, they want to know how long it will be before they start feeling good again. This month’s Healthwise focuses on post-treatment experiences from people who underwent double therapy, triple therapy, and regimens in clinical trials; some cleared HCV and some didn’t.

As so often happens with treatment, their experiences vary. Just as no one can predict if HCV treatment will be easy or difficult, no one can predict how long it will take to return to “normal” after taking antiviral drugs. Don’t count on feeling good immediately. It takes time, and sometimes it feels like two-steps forward, one-step back.

Some people feel better in a month, some in a year, and sadly, some say they still don’t feel right; most seem to fall somewhere in the middle. Quite a few say that when they did start to feel well, they felt better than they had prior to treatment. When it pays off, it is all worth it. As one patient put it, “During treatment I didn’t know what was up...but now I am 100+%.”

Before I go further, let me state that there is not much research about HCV patients’ post-treatment experiences. One of my favorite organizations, The Hepatitis C Trust conducted a web-based survey post-treatment survey. I appreciate this, particularly because it recognizes an area in which there isn’t much information. However, surveys have limited value, as they are more likely to attract responses from people who might be having issues. People don’t usually look for solutions for problems that are resolved, and thus would not feel the need to complete a survey. The Hepatitis C Trust acknowledges the limits of the survey.

Surveying 500 participants from April 2006 to September 2007, they reported:

  • 90% reported ongoing side effects for longer than 12 months after treatment ended

  • The most frequently reported post-treatment complaints were fatigue, joint aches/pains, brain fog, depression and mood swings

  • Regardless of SVR (sustained virological response), 40% of people felt worse after treatment than before and 31% felt better

  • For those who had attained SVR 37% felt better and 36% felt worse

  • For those who hadn’t attained SVR 18% felt better and 50% felt worse

At first glance, this is discouraging. However, keep in mind that the majority were genotype 1 patients, so presumably had 48 weeks of treatment. Most were between 41 and 60 years old and 87% had symptoms prior to treatment.  

Jodie Fussner of Newburgh, Indiana recovered fairly quickly. “I’m post-treatment almost 3 months and I feel great, although it did take a month or two of drinking lots of water. “ I still have to avoid stress and I have some skin problems.” Daryl Luster of Vancouver, BC wrote, “It took about a year before I felt like I was non-toxic. My treatment was 48 weeks, and I was taking a number of meds to get through treatment that I had never needed before treatment.”

Splitting the difference was Judith Apple of Lake Worth, Florida who said it took six months or longer. “I found that I wasn’t even aware that I felt better until I realized that I could finally take a shower, brush my teeth and get dressed without having to get into bed and resting for 15-30 minutes between tasks.”

It took nearly a year for Bill from Owen Sound, Ontario to feel completely better. “I felt better the day I did not have to give myself the injection. After that, it was a steady progression. First thing I noticed was I did not feel the need to sit as much as I had during treatment. Then I noticed I was not scratching as much. After about 3 months, I really noticed a difference in strength and endurance. I am back downhill skiing and working out at the gym 4 times a week. Still have the virus…for now life is good!”

If that sounds like a long time, consider this: you probably had HCV for a long time. Treatment for it also took a huge slice of time. Some of us may not have realized that we tolerated health problems for years before beginning. As Jodie put it, “I didn’t realize how sick I was all those years when I didn’t know I had hep C.” For many, time feeling lousy is worth trading if they get back a healthier, HCV-free life.

For most, but not all, the sense of taste returns in about a month. Lab results begin to normalize around that time, although it may take much longer before the thyroid stabilizes. Coinfected with HIV/HCV, Kevin Maloney of Albany, New York wrote, “It took a whole year for my white cell count to recover with lots of lingering fatigue and anxiety.”

Just because your labs are normal doesn’t mean you feel normal. It can be reassuring to have normal results but simultaneously frustrating not to have a visible explanation for why you feel lousy. Never let a lab or your medical provider tell you how you should be feeling.

“Move on as quickly as possible. Start doing the things you love to do, put the treatment behind you. Look for the improvements not the residual effects of treatment. Don’t dwell on the crappy side of treatment. It’s over for good or bad.”

Hair loss usually stops three months into treatment. The length of time it takes for the skin to heal can take months. Natalye Harries of Swansea, South Wales writes, “I am 4 months post treatment (which failed) and only now is my skin getting back to normal.”

Chronic aches seem to linger more than just about any other side effect. Natalye’s aches resolved quickly, perhaps because she is 38 years old. Baby Boomers who are in their 50’s or 60’s may not recover as easily, especially after long bouts of being sedentary. Older adults have a very small margin of time before their muscles atrophy, bones lose calcium, and damage sets in.

What might start with a small ache may proceed to a cascade of serious consequences.

Some patients have a difficult aftermath. With eighteen blood transfusions, Florida resident Sonya Mallard faced serious challenges during HCV treatment. Two months after finishing, Sonya writes, “I am experiencing severe leg pains causing my legs to give out at times, memory problems, and still fatigued. I am also experiencing diarrhea, vomiting, neck/shoulder pain, and the sun is still affecting my eyesight. I rest when necessary.”

Recovery from treatment may be complicated by which side effects you have, how healthy you were to begin with, and how committed to healthy habits you are. For instance, an overweight smoker who doesn’t exercise might not ever feel right, where someone who says, “I did this and now I am going to stay healthy and exercise and keep my weight down” may do well. Then there are those sad stories of people who did everything by the book but can’t seem to feel good.

Healing from combination therapy was harder for me than the treatment. I could blame interferon for my post-treatment aches. However, common sense tells me the problem was months of inertia, poor back support from the couch, and six months without a single ab exercise.

Although I was a responder-relapser, once I felt better, it was a noticeable improvement from before I started. However, I lost a significant amount of weight during treatment. I vowed not to regain it, so when I could, I started exercising more regularly. I can’t tell you if I feel better because of the treatment or because now I am in better condition, but I sure do appreciate the difference.

Recuperation may be complicated by multiple medical conditions. At three weeks post-treatment, Oh My Aches and Pains blogger Selena Inouye said, “I am still dealing with some side-effects like anemia and a couple of ways treatment made my pre-existing conditions worse. I knew going into this that both of these things could happen, so I am not surprised.”

If you have never experienced treatment, this article may seal your decision to avoid it. Before you do, consider this: some of these patients, along with hundreds of thousands of others in the U.S., have gone through treatment more than once, some three or more times. As awful as the side effects and aftermath are, they aren’t bad enough to discourage these folks.

Although Bill did not clear HCV, his advice works for everyone. “Move on as quickly as possible. Start doing the things you love to do, put the treatment behind you. Look for the improvements not the residual effects of treatment. Don’t dwell on the crappy side of treatment. It’s over for good or bad. Fresh air, exercise, local food, hobbies, projects all help to move forward.”

One post-treatment element that is a challenge for most everyone is waiting for results. Jodie admits what most feel, “I am a bit stressed over having to wait until December to find out if I’m still clear. I try to think positive, but it’s hard after what I went through.” Daryl echoed these sentiments. “I just tried to not worry, but it was impossible to not think of it from time to time. What works best for me is to try my best to live in the now, and not dwell too much on what might be, or what might have been. It is not always easy for me to do, but I do try my best and it does help me.”

As this article was going to press, Daryl’s 18-month follow-up lab confirmed he remains free of hepatitis C.

Lucinda K. Porter, RN, author of Free from Hepatitis C is a long-time contributor to the HCV Advocate. Her blog is
http://lucindaporterrn.com

 

Further Reading:

 

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Type 2 Diabetes and Insulin Resistance in People with HCV – Part 1
—Liz Highleyman

Diabetes is a condition in which blood sugar levels are too high. This can occur when the body does not produce enough insulin or when cells do not use insulin properly, known as insulin resistance. People with chronic hepatitis C virus (HCV) have an increased risk of insulin resistance and type 2 diabetes, but the reasons are not fully understood.

Glucose and Insulin
The body needs a type of sugar called glucose as fuel to provide energy. When food is digested and broken down, glucose is released into the bloodstream. In order for cells to use glucose, they require a hormone called insulin which acts as a key that allows it to enter cells. Insulin is produced by beta cells located in the Islets of Langerhans in the pancreas.

Blood glucose levels fluctuate over the course of the day. Normally blood sugar rises after eating but soon returns to a lower level. But if there is not enough insulin present – or if cells cannot use it – glucose remains at elevated levels in the bloodstream, a condition known as hyperglycemia, leaving cells throughout the body starved for energy.

There are two major types of diabetes mellitus, better known simply as diabetes:

  • Type 1 diabetes, formerly insulin-dependent or juvenile diabetes, typically develops during childhood. People with this type of diabetes produce little or no insulin, often because beta cells have been destroyed by an autoimmune reaction. They usually must inject insulin daily or use an insulin pump.

  • Type 2 diabetes, formerly non-insulin-dependent or adult-onset diabetes, usually develops later in life. People with this much more common type of diabetes generally have progressive insulin resistance, but they also may not produce enough insulin. Insulin resistance and type 2 diabetes are managed with diet, exercise, and oral medications or insulin.

Gestational diabetes refers to diabetes that develops during pregnancy and diabetes insipidus is a separate condition characterized by excessive urine production by the kidneys; these types will not be discussed further here.

How Common is Type 2 Diabetes?
The Centers for Disease Control and Prevention (CDC) estimates that in 2010 more than 25 million people in the U.S., or about 8% of the population, were affected by diabetes, with nine out of ten cases being type 2. Only about one-quarter, however, have been diagnosed. The risk of type 2 diabetes increases with age  reaching nearly 30% for people 65 years or older – but rates are also rising among children and adolescents.

As many as 80 million Americans – about 35% of the population over age 20 and 50% of those over age 65 – are thought to have milder blood glucose elevation known as pre-diabetes.

Type 2 diabetes affects similar numbers of men and women. However, it is significantly more common among African Americans, Latinos/Hispanics, Asians/Pacific Islanders, and Native Americans compared with whites; according to the CDC, the risk of diabetes diagnosis is 18% higher among Asian Americans, 66% higher among Hispanics, and 77% higher among blacks. Genetic, socioeconomic, and lifestyle factors are all thought to contribute to this disparity.

Insulin Resistance and Diabetes Risk Factors
Insulin resistance and type 2 diabetes are associated with obesity and often occur in conjunction with a cluster of manifestations (including high blood pressure and abnormal blood lipid levels) known as the metabolic syndrome. A sedentary lifestyle and ready access to high-calorie and high-fat food is thought to be largely responsible for the dramatic increase in the prevalence of diabetes in recent decades.

The exact mechanism underlying insulin resistance is not fully understood. It may be related to defects or impaired function of cells’ insulin receptors, or perhaps changes in signaling inside the cell. Some research, for example, suggests that resistin, a cytokine produced by adipose (fat) tissue, interferes with the action of insulin as well as playing a role in inflammation.

Symptoms and Complications
Symptoms of diabetes (both type 1 and type 2) may include increased thirst and appetite, frequent urination, and unexplained weight loss. Others may experience early signs of complications, such as fatigue, mental confusion, blurred vision, or sores that are slow to heal.

But many people have no symptoms related to insulin resistance, pre-diabetes, or early type 2 diabetes, and they are only diagnosed with blood tests.

Various tests are used to diagnose diabetes. Fasting plasma glucose is measured after a person has gone without food for eight hours. A level of 100 to 125 mg/dL is considered pre-diabetes and 126 mg/dL is the threshold for diabetes.

An oral glucose tolerance test is used to determine whether glucose levels rise and fall normally after consuming a sugar solution. With this method, 140 to 199 mg/dL is considered pre-diabetes and 200 mg/dL is the threshold for diabetes.

A hemoglobin A1c test (also known as glycosylated hemoglobin) measures how much sugar adheres to hemoglobin molecules in red blood cells. It reflects average blood sugar levels over the past two to three months, so it can give a more accurate picture of blood sugar control than tests done at a single time point. A1c values of 5.7% to 6.4% reflect pre-diabetes and 6.5% or greater indicates diabetes.

The homeostatic model assessment, or HOMA-IR, is a method of estimating insulin resistance using fasting glucose and fasting insulin levels. Two other methods of determining insulin sensitivity, the hyperglycemic and euglycemic clamp techniques, are more accurate, but also more difficult and expensive.

Insulin resistance and type 2 diabetes tend to progress over time, explaining why rates are higher among older individuals. Beta cells’ ability to produce insulin may diminish over time, while cells throughout the body may become less sensitive to its effects.

Over years or decades elevated blood sugar can contribute to a variety of serious complications including cardiovascular disease, kidney dysfunction, nerve damage (diabetic neuropathy), gum disease, pregnancy complications, and vision loss due to diabetic retinopathy. Nerve and blood vessel damage can lead to pain or numbness in the hands and feet, sexual dysfunction, and poor wound healing.

According to the CDC, diabetes is the most common cause of kidney failure, non-traumatic lower-limb amputations, and blindness among adults in the U.S., as well as a major cause of heart attacks and strokes, and the seventh leading cause of death.

Definitions: mg = milligram, dL = deciliter
For all three tests, within the prediabetes range, the higher the test result, the greater the risk of diabetes


Source: Adapted from American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(Supp 1):S12, table 2.

 

Hepatitis C and Diabetes
Starting in the 1990s researchers began to report that people with chronic HCV infection were more likely to have insulin resistance or type 2 diabetes, and vice versa. Recent estimates suggest that 30% to 70% of individuals with chronic hepatitis C show some evidence of insulin resistance.

In 2000, for example, Shruti Mehta and colleagues from Johns Hopkins reported findings from an analysis of medical records of nearly 10,000 people taking part in the National Health and Nutrition Examination Survey. After controlling for race/ethnicity, injection drug use, and other factors, they found that among people age 40 and older, those with hepatitis C were nearly four times more likely to have type 2 diabetes. 

Due to this increased risk, some experts think people with chronic hepatitis C should be routinely tested for insulin resistance and type 2 diabetes.

“Utilization of oral glucose tolerance testing has the potential to uncover previously undetected diabetes mellitus as well as impaired glucose tolerance or pre-diabetes in patients with chronic hepatitis C,” wrote Ayse Aytaman and Samy McFarlane in a 2008 editorial in the American Journal of Gastroenterology. “Early detection of diabetes and pre-diabetes with oral glucose tolerance testing in chronic hepatitis C patients can lead to interventions, with significant positive impact on disease progression and antiviral therapy outcomes.”

Several hypotheses have been proposed to explain why type 2 diabetes is more common among people with hepatitis C. Controlled analyses have shown that the difference is not attributable to more medical procedures or more frequent HCV testing leading to higher rates of hepatitis C infection or diagnosis among people with diabetes.
Some experts have suggested that HCV may infect insulin-producing beta cells, or they may be damaged by immune responses triggered by HCV. Similarly, immune modulation caused by interferon-based hepatitis C treatment may adversely affect beta cells. Furthermore, liver inflammation, fibrosis, or steatosis (fat accumulation) due to HCV may affect glucose production or insulin metabolism.

Some research indicates that liver cirrhosis regardless of cause increases the risk of insulin resistance. However, a study by Nizar Zein and colleagues from the Mayo Clinic showed that patients with end-stage liver disease related to HCV or heavy alcohol use had much higher rates of type 2 diabetes than people with liver failure due to cholestasis (decreased flow or blocked bile ducts). Researchers in Taiwan recently reported that having diabetes may increase the risk of hepatocellular carcinoma in people with chronic hepatitis C, even after sustained response to interferon/ribavirin.

A consistent body of research has shown that not only are people with hepatitis C more likely to have insulin resistance and type 2 diabetes, but these conditions are significantly associated with poorer response to interferon. But some studies suggest that insulin resistance improves after successful HCV treatment, and conversely, managing insulin resistance or diabetes may improve prospects for curing hepatitis C.

A recent study by Albert Friedrich Stättermayer from the Medical University of Vienna and colleagues found that hepatitis C patients who carry the IL28B rs12979860 “T” allele are more likely to have insulin resistance than those with the favorable “C/C” gene pattern, which may help explain their poorer response to interferon. Further study is needed to clarify whether the new direct-acting anti-HCV drugs will help overcome this disadvantage.

Like HCV, HIV infection and its treatment are also associated with higher rates of insulin resistance and diabetes, and thus HIV/HCV coinfected people may be at particularly high risk. A 2012 study by the Canadian Co-infection Cohort Study team found that 56% of non-diabetic study participants had insulin resistance with a HOMA-IR score of 2 or higher, and people with insulin resistance were more than twice as likely to develop significant liver fibrosis.

Resources

  • American Diabetes Association: www.diabetes.org

  • Centers for Disease Control and Prevention:
    www.cdc.gov/diabetes

  • CDC. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011.

  • National Diabetes Information Clearinghouse/NIDDK: www.niddk.nih.gov/health/
    diabetes/diabetes.htm
     

  • National Diabetes Information Clearinghouse. Diagnosis of Diabetes and Prediabetes. Last updated August 29, 2012.

Part 2 of this article will focus on managing diabetes and will appear in the November 2012 Issue of the HCV Advocate newsletter

 


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Hepatitis C Support Project

2012 Hepatitis C Support Project

Medical  Writers' Circle
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