Thursday, April 6, 2017

Hepatitis C Fatigue - What's that all about?

Hepatitis C Fatigue - What's that all about?
Fatigue is the most commonly experienced symptom in people with liver disease, and it has a significant impact on their quality of life.  Hepatitis C is a major cause of chronic liver disease in the United States, with fatigue reported as the most frequent disabling symptom - in over one-half of all people diagnosed with the virus.

In this post we look at available research and possible related conditions that may contribute to that all too familiar symptom.

Let's start with a recent study which examined whether HCV fatigue, depression and health-related quality of life improves after successful HCV therapy. The result?  Well, not always.

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?
Previous research has shown that fatigue from chronic hepatitis C usually decreases after achieving a sustained virologic response (SVR), however, occasionally fatigue may still persist after patients clear the hepatitis C virus. In a study published in Journal of Viral Hepatitis February 2017, researchers evaluated chronic fatigue after successful virus eradication. In the study researchers enrolled 159 individuals with HCV, without advanced liver disease. Patients answered a series of questions about fatigue, depression, coupled with various attention and memory tests. The patients were divided into 4 groups according to their viremia (presence of HCV virus in the blood) and interferon treatment history. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. The results suggest that HCV infection may cause long-standing cerebral dysfunction that significantly impairs health-related quality of life that may persist even after virus clearance. Commentary on the study written by Stephanie Finucane, MS, CMPP summed up the results nicely, the author wrote;
Disabling chronic fatigue is reported in approximately 60% of patients with confirmed hepatitis C virus (HCV) infection, as well as decreased quality of life and cognitive dysfunction (eg, deficits in attention and verbal learning). While these neuropsychiatric symptoms may be expected in patients with ongoing HCV infection, it is questionable whether these effects are also present in HCV-exposed patients who currently are cured of the infection.
A study recently published in the Journal of Viral Hepatitis found no evidence linking the presence of HCV infection with these neuropsychiatric symptoms. Instead, researchers suggest that the fatigue and impairment in health-related quality of life (HRQoL) and cognitive and mental function commonly found in HCV-exposed patients may be explained by either an HCV infection-triggered autoimmune response persisting beyond virus clearance or the development of a virus variant in the brain.  
Commentary here, full text article here.

Other Contributing Factors
Other contributing factors may include lifestyle, pre-existing conditions, coping with the diagnosis, loss of employment, medical coverage, and the cost of expensive HCV medications, all of which can cause depression and anxiety leading to fatigue, yet these conditions are frequently overlooked when patients seek out medical care.

Extrahepatic Manifestations
Fatigue can be caused by other conditions related to the virus, although hepatitis C infection primarily affects the liver, 40% of patients with HCV will develop at least one extrahepatic manifestation (conditions that affect organs other than the liver) during the course of their disease.

The most prevalent and most closely linked extrahepatic manifestation found in hepatitis C patients is essential mixed cryoglobulins causing dermatologic, neurologic, renal, and rheumatologic complications. Cryoglobulinemia happens when abnormal proteins in the blood solidify in cold conditions. In patients with mixed cryoglobulins, 35 to 54% reported various symptoms that include but not limited to fatigue, joint pain, muscle pain, itching, rashes, tingling in hands and feet. Non-cryoglobulin diseases with a less definite relationship to HCV include systemic vasculitis, splenic lymphoma, porphyria cutanea tarda, and the sicca syndromes.

International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement
A paper published in Autoimmunity Reviews March 2017, set out to investigate what effects new HCV interferon-free and old interferon-based antiviral therapy may have on different HCV-extrahepatic manifestations (HCV-EHMs). The effect of Non-viral therapies on HCV-extrahepatic manifestations were also included in the article. In summary the article reported that compared to interferon-based therapy, interferon-free antiviral therapy caused minimal reduction in patient-reported outcomes during therapy and improvement of vitality and fatigue at SVR12. As stated in the abstract: In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches.
Full Text - Download PDF

Recommended Reading
Patient Reported Outcomes Critical in the Fight Against HCV
HCV Next, March 2017
Zobair M. Younossi, MD, MPH
When you look at the consequences of any chronic liver disease such as hepatitis C, three different types of impact emerge. The first impact is the clinical consequences of HCV infection. The clinical impacts of HCV can further be divided into hepatic manifestations like cirrhosis and liver cancer and extrahepatic manifestations of HCV infection such as cryoglobulinemia, chronic fatigue and diabetes. Both the hepatic and extrahepatic complications of HCV infection can lead to excess mortality and ultimately impact patient’s survival. In this context, clinical outcomes of HCV can be surrogates for survival.

The second type of impact of HCV infection is captured by patient reported outcomes, or PROs. PROs are reported directly by the patient without any changes or modifications by the physician or caregiver. PRO is an umbrella term that includes everything from health-related quality of life (HRQoL), functional status and even stigma associated with HCV infection. PROs are surrogates for the patients’ experience with their disease and its treatment. If you improve PRO scores, you are improving the patient experience with their disease.

The third type of impact of HCV infection is related to its economic consequences, which can include direct, indirect or intangible costs of the disease and its treatment. In this context, the economic impact represents a surrogate for resource utilization.

When you consider these three impacts of HCV infection together, you get a complete and comprehensive picture of HCV infection and its impact on the individual patient and the society.
Continue reading...

An Overview of Extrahepatic Manifestations of Hepatitis
A patient friendly fact sheet explaining conditions associated with HCV including symptoms.
Direct-acting Antivirals Effective for HCV-related Mixed Cryoglobulinemia

Recently published in Journal of Advanced Research is a nice collection of review articles on the extrahepatic manifestations of HCV.

Thyroid Disease
According to the American Thyroid Association (ATA). About 20 million Americans—more of them women than men—are affected by a thyroid disease or disorder. In fact, an estimated one in eight women will develop a thyroid disorder at some time in her life.

Hypothyroidism & Hyperthyroidism: Symptoms
Hyperthyroidism - When your thyroid gland makes more thyroid hormones than your body needs.
Symptoms of Hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of your skin, fine brittle hair and weakness in your muscles—especially in the upper arms and thighs.
Hypothyroidism - When your thyroid gland does not make enough thyroid hormones
Symptoms of Hypothyroidism may include feeling cold, fatigued, dry skin and forgetfulness.

Thyroid Disease And HCV
Before approved interferon-free medicines were available in the U.S. to treat HCV, thyroid dysfunction (interferon induced thyroiditis) was a common side-effect of interferon-based therapies. However, hepatitis C itself can cause thyroid changes, even in people that have never treated with interferon.

Chronic HCV infection is associated with several endocrine disorders (diseases related to the endocrine glands), for example the most frequent is thyroid disorders and type 2 diabetes. Thyroid imbalance and thyroid anti-bodies are much more common in patients with Hepatitis C virus infection than in people without the virus.  According to a 2016 study the hepatitis C virus shares some molecular similarities with the thyroid and this may make the immune system mistakenly attack the thyroid gland in response to the presence of foreign molecules coming from the virus. The virus could also be infecting the thyroid cells and that could trigger the attack of the immune system on the thyroid gland.

Thyroid Disturbance in Patients with Chronic Hepatitis C Infection: A Systematic Review and Meta-analysis
In a review article published in Journal of Gastrointestinal and Liver Diseases June 2016, researchers looked at literature dated up to August 2015 to identify observational studies which compared thyroid dysfunction in interferon naïve HCV-infected and non-HCV infected subjects. The study confirmed HCV infection may be an independent risk factor for thyroid disturbance independent of administration of interferon therapy. Download the article, here.

Recommended Reading
Hashimoto’s disease

Depression and anxiety is often associated with a diagnosis of a chronic illness, especially with a serious chronic disease like hepatitis C. As a result of having HCV, symptoms may already exist, for example disturbed sleep, impaired appetite, and joint pain, these ongoing symptoms decrease quality of life and increase fatigue.

A Warning
Experts warn, if depression was present before being diagnosed with HCV a distinction between an adjustment reaction and a depressive illness should be determined by your health care provider.

Moving Forward
The phrase “knowledge is power” is a profound one to be sure, especially when applied to hepatitis C. Acquiring knowledge about hepatitis C can lead to an early diagnosis, a cure, and important management strategies to treat complications of this sometimes life-threatening virus.

Educating yourself about the virus will put control back into your life, test results become easier to understand, discussions with your health care professional about managing or treating the virus will be more productive, this is turn may elevate anxiety. Once all this is in place a plan of action begins. If treatment is considered, the next hurtle can prove to be difficult, many insurance companies and state Medicaid programs limit treatment to those with the most severe cases of HCV, the good news is that this is improving, but it's taking far too long.

Recommended Reading

Anxiety And Trump
At the moment possible changes in regard to the proposed replacement for the Affordable Care Act under the current administration is enough to cause a healthy person extreme anxiety, to say the least, here is the latest on the subject.

Recently, TAG-Treatment Action Group launched their spring issue of TAGline, with this informative article; Wrangling Affordable Drug Pricing and HCV Elimination Under the New White House Administration.

Baby Boomers
Personally, I consider age an important factor in relation to stress and fatigue, baby boomers, people born between 1945 (age 72) and 1965 (age 52) account for about 80 percent of chronic hepatitis C cases in the U.S.  This segment of the population are sandwiched between raising children and taking care of loved ones, including aging parents, the latter can be at times overwhelming, plagued with grave depression and severe anxiety. In addition, other health issues arise as we age; diabetes, arthritis and heart disease, to name a few.

Identifying Contributing Factors Associated With Fatigue
Depression can drain your energy, leading to lack of sleep which may start a vicious unhealthy cycle. As for anxiety, well that is just exhausting. By first identifying these possible contributing factors, you can then begin to use coping tools that help relax or even energize you. Setting limits on what you’re able to handle is probably the best advice - learn to say no. Eventually, try doing little things like going for a walk, or reading about ways to manage stress, these small steps go a long way on the road back to wellness and may improve fatigue.


Until next time, wishing you all a safe and healthy journey.

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