Hepatitis C, stigma and cure Being diagnosed with hepatitis C is overwhelming enough, the negative stigma associated with the disease is nothing short of debilitating. Sadly, our culture is a culture of blame, particularly surrounding drug use, the biggest stigma linked to the virus.
Additional psychological distress caused by living with a stigmatized disease can get in the way of initial HCV testing, an important first step toward ensuring optimal care to avoid possible liver damage. Only after knowing your hepatitis C status can steps be taken to seek out life-saving treatments.
Hepatitis C, stigma and cure
Recently, an article titled "Hepatitis C, stigma and cure" published in the October issue of World J Gastroenterol, looked at the social stigma attached to HCV, consequences of living with the chronic infection, and new drugs to treat the virus.
The global hepatitis C epidemic is estimated to include 130–170 million people worldwide. In the United States an estimated 2.7–3.9 million people are living with the virus, more than 2 million of these people are baby boomers, with around 75 percent unaware they are infected - because they haven't been tested. In a year, 80,000 new infections will occur and close to 15,000 Americans will die from the disease.
New Drugs
The disease is curable, especially with so many new drugs making their way to FDA approval. I assume that if you're reading this post then you probably already know recently the Antiviral Drugs Advisory Committee reviewed two new agents.
The FDA does not have to follow the advice of its panels, but most often will. The U.S. health regulators are scheduled to decide whether to approve sofosbuvir by Dec. 8, and simeprevir by Nov. 27.
With interferon-free therapies so close to FDA approval and so many in clinical trials the promise of treating hepatitis C without interferon is becoming a reality. According to new data from this months AASLD meeting in Washington, new agents have been shown in clinical trials to shorten treatment duration, lower toxicity and improve efficacy.
Interferon-Free Genotype 1
This week published online in "The Lancet" researchers suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV including those with compensated cirrhosis or who have previously failed treatment with protease inhibitors.
The Links
AASLD - Updates
Check Out - Interferon Free Combinations
AASLD Website
Browse Abstracts
AASLD Coverage
Commentary/Abstracts/Videos @ Healio
Capsule Summaries, review by experts and slides @ Clinical Care Options CCO
CME/CE with commentary by Michael Smith @ MedPage Today
Commentary/Abstracts with coverage by Liz Highleyman @ hivandhepatitis.com
Slides/Abstracts @ NATAP
Check Out - Interferon Free Combinations
AASLD Website
Browse Abstracts
AASLD Coverage
Commentary/Abstracts/Videos @ Healio
Capsule Summaries, review by experts and slides @ Clinical Care Options CCO
CME/CE with commentary by Michael Smith @ MedPage Today
Commentary/Abstracts with coverage by Liz Highleyman @ hivandhepatitis.com
Slides/Abstracts @ NATAP
Rui Tato Marinho and David Pires Barreira.
Keywords: Hepatitis C, Chronic, Therapy, Hepatocellular carcinoma, Hepatic
cirrhosis, Interferon-alpha, Ribavirin, Social stigma,
Depression
HEPATITIS C AND CURE
Step by step increasing the efficacy
Hepatitis C is one of the most important global chronic infection
worldwide: it is estimated to affect 170-200 million people, while chronic
hepatitis B and human immunodeficiency virus (HIV) infection affects
respectively 350 million and 34 million. There is no vaccine for hepatitis C.
Hepatitis B is easily preventable by vaccination. Another characteristic of
hepatitis C virus (HCV) infection is the high risk of evolution to chronicity,
more than 50% which can be around 80% in same series[1]. Another
characteristic is the absence of symptoms for decades before the phase of
decompensation of liver cirrhosis and the appearance of hepatocellular
carcinoma.
The most severe chronic consequences of the infection are liver
cirrhosis and hepatocellular carcinoma, leading to hepatic failure and death,
which can appear in 20%-40% of the patients[2].
In effect, cirrhosis is the end-stage of every chronic liver
disease. Its natural history is characterized by an asymptomatic phase, called
“compensated” followed after several years or decades by a “decompensated”
phase. The patient, in the decompensated phase has a median of survival of 2
years[3].
This phase can be characterized by a rapid clinical evolution with
all the complications of a cirrhotic liver with portal hypertension: ascites,
sepsis (the majority from spontaneous bacterial peritonitis), varices bleeding,
jaundice, mental alterations (encephalopathy), renal failure (hepatorenal
syndrome), caquexia[4,5].
Liver cirrhosis is one of the most oncogenic situations in medical
terms. The development of hepatocellular carcinoma (HCC) is a real fact,
occurring in 1%-4% each year and is becoming in some centers the most frequent
complication of HCV cirrhosis[6].
The quality of life in the decompensated phase can be very poor
with frequent hospitalizations and readmissions[7]. At this
stage only liver transplantation is really effective for median or long term
survival. But if the virus is still active, the reinfection is almost
universal[8]. But, besides the “drama” of being infected, health
professionals, family, society and infected patients, must be aware of the
chance of real cure and total and definitive elimination of the virus[9].
The HCV was discovered 25 years ago in 1989, is a RNA virus and
classified by the World Health Organization as an oncogenic one[10]. The
discover of the virus has open the way to a diagnosis test (anti-HCV) and
several studies of molecular biology, virology and pharmacology[11]. The
treatments for hepatitis C has begun in the last 80´s with a percentage of cure
of 6%[12]. Step by step the efficacy of the therapy for hepatitis
C is rapidly increasing and nowadays with the very new medications, the oral
Direct Antiviral Agents-DAAs, is around 80%-90%[13].
The therapy of hepatitis C is an example of the capacity of modern
medicine to translate the basic research to the clinical setting (Figure 1). Several types of
medications have been used in to treat hepatitis C throughout these 25 years of
success: first, human interferon (INF, three times weekly, 6% of efficacy), in
1995 Ribavirin has appeared to be used in combination with INF (34%-42% of
efficacy), in 2001 Pegylated INF once weekly with ribavirin (45% of cure for
genotype 1 and 70%-80% for genotype 3)[14]. In 2011 another step with the combination
of Peginterferon and Ribavirin with two Protease inhibitors, region 3/4
(Boceprevir[15] and Telaprevir[16]), the triple therapy, leading to cure in
70%-80% of cases.
Figure 1
Percentage of cure of hepatitis
C genotype 1. IFN: Interferon; RBV: Ribavirine; PEG: Peginterferon; DAA: Direct
antiviral agents.
Several clinical trials are in rapid development worldwide with the
new DAA´s (Direct Acting Antiviral Agents) interacting with several of vital
components of the virus (NS 3/4, NS5A, NS5B Polymerase, etc.). In
effect a new generation medications is rapidly approaching, like
Sofosbuvir[13], Daclastavir, Asunaprevir[17],
ABT-450[18], Faldaprevir, Simeprevir, Deleobuvir, some of them only
using oral agents, for a period of 12 wk, with a few negligible side effects,
having a chance of viral eradication of 80%-90%.
In fact, in a quarter of a century, the percentage of cure has
increased from 6% to 90% of cure. From three injections a week during 48 wk to
some pills a day during 12 wk! Another important development that has positively
affected the quality of life of patients, allowing access to treatment and
possible cure is the Transitory Elastography (Fibroscan®). Is an
ultrasonographic device with very good acuity in the diagnosis of liver
fibrosis, mainly when there is liver cirrhosis. The number of liver biopsies has
decreased[19] in some centers around 90%.
The efficacy of the therapy is assessed by on important finding,
i.e., the viral load: RNA HCV (by a sensitive test) must be negative 24
wk after stopping therapy. If this happens, more than 99% of patients will never
be positive again.
Cure of hepatitis C
It is the only global chronic viral infection that is possible to
cure. The other ones are hepatitis B and HIV infecting respectively 350 and 34
million people worldwide but with no chance of cure in chronic cases.
In the beginning of this story of success, the medical community
was afraid of the word cure. But now it is well known this word can be used with
property but with some restrictions. In effect is a virological cure for life.
It is proved that virus is not detected on liver cells or mononuclear blood
cells. Nor there is an occult disease as is the case for chronic hepatitis B
(HBV DNA negative or with low levels, having HBsAg negative and a risk of
relapse in case of immunosuppression).
Albeit is a definitive one, we must be cautious in patients having
liver cirrhosis, because the chance of development of hepatocellular carcinoma
is strongly reduced, but still remains. It is one of the reasons to treat
patients with mild or moderate fibrosis, in order to reduce the chance, while in
a stage of a less severe disease, of evolution to cirrhosis and hepatocellular
carcinoma. Liver cirrhosis, per se, is a disease having a risk of 1%-4%
per year of evolution to hepatocellular carcinoma.
The benefits of cure are tremendous. Hepatitis C should be
considered a global disease. As for the definition of Health of World Health
Organization, (“Health is a state of complete physical, mental and social
well-being and not merely the absence of disease or infirmity”) chronic
hepatitis C is a physical, mental and social disease, affecting globally the
individual, the couple, the family, and the society as a whole.
There are some myths about hepatitis C: “almost always lethal, more
severe than acquired immunodeficiency syndrome (AIDS), very contagious disease,
not curable, the adverse events of therapy are huge and very severe,
etc.” But the benefits of cure, in global terms considering the
physical, mental and social aspects are several (Table 1).
Table 1
Benefits of cure of hepatitis C
| Benefits of cure of hepatitis |
| 1 Negative HCV RNA (viral load) for life, in more than 99% of cases |
| 2 Negative HCV RNA in the liver |
| 3 HCV RNA negativation in PBMC |
| 4 No detection of the genotype |
| 5 Sometimes, a few year later, the anti-HCV test can became negative, the so called “seroreversion” |
| 6 Normalization of aminotransferases (AST, ALT) and GGT |
| 7 Changing of ultrasound findings (contours can became regular, reduce of diameter of portal vein in case of portal hypertension) |
| 8 Disappearance of the lymphnodes near the liver (helium) |
| 9 Decrease of the values for Elastography (Fibroscan®) |
| 10 Reducing the risk of progression to cirrhosis |
| 11 Reversion of cirrhosis in some cases |
| 12 Disappearance of oesophageal varices |
| 13 Reducing the risk of progression to liver cancer |
| 14 Reduced risk of decompensated liver disease (ascites, jaundice, rupture of oesophageal varices, encephalopathy) |
| 15 Reducing to zero the risk of recurrence after liver transplantation (if necessary) |
| 16 Improved quality of life (asthenia, fatigue, general well-being) |
| 17 Reducing of the psychological impact (anxiety/depression) |
| 18 Disappearance of the risk of sexual transmission |
| 19 Disappearance of the risk of perinatal transmission |
| 20 Decrease in the insurance premium |
| 21 Cure of associated conditions (porphyria cutanea tarda, polyneuropathy, urticaria, cryoglobulinemia, splenic lymphoma) |
| 22 Reducing personal, family and social stigma |
| 23 The treatment is proved cost-effective |
| 24 Benefit to public health |
| 25 Reduced risk of death from liver disease |
| 26 Neurocognitive improvement |
| 27 Cure of hepatitis C |
Benefits of virological response (HCV RNA negative 24 wk
after finishing therapy). HCV: Hepatitis C virus; PBMC: Peripheral Blood
Mononuclear Cells; AST: Aspartate aminotransferase; ALT: Alanine
aminotransferase; GGT: Gamma-glutamyl transferase.
Mental health and quality of life in hepatitis
C
Besides the natural history of this disease, the personal impacts
of a diagnosis of hepatitis C infection and its treatment strongly affect the
patients’ quality of life[20-22]. Mental health problems frequently occur in
chronic infection with HCV and during the antiviral treatment. These individuals
frequently present neuropsychiatric symptoms like fatigue, anxiety, depression
and cognitive disorders[23,24].
Regarding neuropsychiatric symptoms, one can identify two
distinctive patterns in its relation with HCV infection. On one hand,
individuals with chronic hepatitis C have higher prevalence of psychiatric
disorders, including depression[25]. On the other hand, individuals with
psychiatric records present higher HCV infection rates than the average
population[26].
A combined therapeutics using Pegylated IFN is commonly used in
these patients and proves to be a fundamental and consensual intervention for a
favourable change in the natural history of the disease[27,28].
However, this treatment is associated with a high number of adverse
reactions like: irritability, insomnia, fatigue and loss of appetite. Apart from
these, neuropsychiatric symptoms (especially depression, and sometimes with
suicidal ideation) are among the most common secondary effects in therapeutics
with IFN, being one of the main causes why patients interrupt their
treatment[24,29,30]. It is
noteworthy that, up to a certain extent, psychopathologic symptoms (depression,
cognitive disorders) may be associated to HCV infection, even without an INF
treatment, and may be related to direct HCV neurotoxicity[29-32].
A large number of patients undergoing treatment for VHC infection
should be referred for psychiatric evaluation and, if necessary, should received
treatment for depression and other neuropsychiatric symptoms.
Recognition of depression and other neuropsychiatric symptoms is
important, and could improve adherence to VHC treatment. This symptomatology
negatively affects the individual’s perceived quality of life, its general
functioning, work capacities, less participation in life and medical care,
increase mobility and mortality, decrease overall well-being and quality of
life[27,33]. Furthermore, therapeutic used in HCV
treatment is associated to impairment in all of these dimensions[34].
Thus, considering the impact in patients’ mental health, before and
during the treatment, an interdisciplinary approach should be followed and
encouraged when dealing with HCV infected patients[24].
Stigma and hepatitis C
Diagnosis with hepatitis C was reported to have profound impacts on
social functioning. Perceived stigma associated with HCV infection leads to high
levels of anxiety and exaggerated fear of transmission, and it can be a major
cause of social isolation and reduced intimacy in relationships[35].
Epidemiological studies suggest that more than 90% of transmission
in developed countries takes place through the sharing of non-sterilized needles
and syringes in the intravenous drug-using population[36].
Because the vast majority of people with hepatitis C have a history
of intravenous drug use, they are frequently blamed for acquiring the disease,
and viewed as irresponsible, accountable and “unworthy”[37].
Furthermore, as a blood-borne disease, hepatitis C is strongly associated with
HIV. This association exists due to the fact that intravenous drug abuse is a
significant risk factor for contracting both diseases and this can be a
stigmatizing factor for this patients[38]
Stigma can be defined as attitudes expressed by a dominant group,
which views a collection of others as socially unacceptable. The notion of
stigma denoting shameful relations and deviations from what is considered
“normal” has a long history within infections disease, in particular HIV[39], and more
recently in hepatitis C infection.
These norms, behaviours and beliefs surrounding hepatitis C
infection can lead to alienation from family and friends, as well as to
discrimination (perceived or real) in health services and workplaces[40].
Stigma can affect self-esteem and quality of life. It can also
impede the success of diagnosis and treatment, leading to continuing risk of
disease transmission. It is a social phenomenon that influences the course of
illness and marginalizes patients[41].
Since stigmatization affects not only the individual but also the
whole course of the disease, health care workers are not immune to stereotypes
and judgements that might influence the course of the treatment of HCV patients.
Changing this behaviour will help prevent patients’ isolation, withdrawal of
treatment and it will increase the search for medical help[42].
Hepatitis C should have a global approach in its treatment. It
requires broad-based educational efforts in order to increase the understanding
of this disease, still connected to several pejorative stereotypes[42]. These
efforts should include patients and their family, health care providers and the
society as a whole. Further knowledge of hepatitis C stigma is central to
assisting patients in self-managing their illness, and it is important to reduce
the disease burden.
Several benefits of cure hepatitis C
The goal of therapy is to eradicate HCV infection. The endpoint of
therapy is sustained virological response (SVR). Once obtained, SVR usually
equates to cure of infection in more than 99% of patients[43].
If the test for assessing viral load is negative 24 wk after
finishing therapy, we can talk of “cure”. With the new treatments, the oral
DAAs, the assessment of sustained viral response can be shortened to 12 wk after
ending the treatment. HCV RNA detection and quantification should be made by a
sensitive assay (lower limit of detection of 50 IU/mL or less), ideally a
real-time PCR assay. If the patient has already cirrhosis, the risk of develop
hepatocellular carcinoma still persist for some years and deserves an abdominal
ultrasound every six mouths.
When the SVR is obtained the global benefit is as it follows: if
there is no another reason for AST, ALT or GGT elevation, namely alcohol
consumption or obesity, they became persistently normal.
At virological level, the HCV RNA is no longer detected in the
liver[44] or even in the Peripheral Blood Mononuclear Cells (PBMC)
by sensitive tests[45]. The genotype becomes and remains negative, because
there is no virus for detection.
One of the things that can cause some confusion is the fact that
the anti-HCV (a marker of past infection) generally remains positive. The index
can decrease slowly and the anti-HCV can became negative, several years after,
as it happens in the context of acute hepatitis C[46].
On the Hepatic Elastography (Fibroscan®) the values
generally decrease along some months[47]. At the abdominal ultrasound the findings
can change: the liver contours can become regular, the diameter of portal vein
reduces in case of presence of portal hypertension. The disappearance of the
lymph nodes in the hepatic hilum can be a finding[48]. There are
some studies showing thatdimensions of these lymph nodes are related with the
levels of viral replication[49].
Regarding liver disease the risk of progression to cirrhosis
decreases. In some cases it occurs a reversion of cirrhosis[50]. In fact
this is no longer an irreversible situation as was thought some years ago; the
disappearance of oesophageal varices is also fact[51]. On the
other side, there is a decrease of risk of evolution for more severe stages of
liver disease like the progression hepatocellular carcinoma[52] and risk
of the decompensated liver disease (ascites, jaundice, rupture of oesophageal
varices, encephalopathy, jaundice, etc.)[53].
In the case that a liver transplantation would be necessary the
risk of reactivation is no longer present. More than 95% of cases of patients
transplanted for cirrhosis associated with HCV will have again HCV RNA positive
and 50% will develop severe forms of liver disease a few years after
transplant[54]. Because of that, to treat patients with cirrhosis or
intense fibrosis must be done as soon as possible.
There is an improvement of quality of life[55] (asthenia,
fatigue, general well-being, etc.) assessed by adequate tests and more
important on the mental level there is a reduction of the psychological impact
(anxiety and/or depression).
In strong relation to cure, the risk of sexual[56] and
perinatal transmission[57] disappear. These are very important advantages of SVR in
the treatment of hepatitis C. We must not forget, that hepatitis C, besides a
liver disease is also an infectious and transmissible disease. We can consider
the cure as “belonging” to the patient himself but also to his family, his
couple, etc. Is also a familiar disease. There are some patients who
don´t tell the family or to the couple afraid of the consequences of the bad
new. If patients insist with Insurance Companies they must decrease the
insurance premium because there is less risk of clinical evolution.
There are reports of the control and even disappearance of some
associated conditions like porphyria cutanea tarda[58],
polyneuropathy[59], urticaria[60], cryoglobulinemia[61], splenic
lymphoma[62,63].
Depending on the countries and the burden of the infection, the
treatment was proved to be cost-effective[64].
Reducingof personal, psychological, family and social stigma is a huge benefit
for all. Stigma is a fact that must be considered in the setting of HCV therapy
and also when considering the real burden of the disease.
CONCLUSION
Considering the global approach we can consider that to cure HCV
chronic infection is a real benefit to public health mainly by reducing the risk
of complications and dying because of liver disease. Having access to the most
modern therapies, the disease is almost a curable disease and the efficacy of
treatment markedly increases the survival of patients infected. Chronic
hepatitis C is a silent epidemic, a global disease with a strong stigma, but
with high chance of definitive cure[65].
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Incredible post - thank you!
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