January 7th, 2009
I have a question relating to hepatitis C especially its diagnosis,
treatment options with costs and patient prognosis. I do not want
information in general but only such information that can help me make
decisions related to the following situation:
A 42 year old Vietnamese man, the husband of a close friend, was
diagnosed as having hepatitis C in June, 2005. He went to a Western
Medical Clinic here in Ho Chi Minh City where western doctors and
Vietnamese doctors trained in the US or Australia practice. I agreed
to pay for his costs.
The diagnosis was hepatitis C. The doctor said that after six months
of weekly shots which cost over $270 for each weekly shot, we could
expect recovery or at least a substantial improvement in his
condition. The shot on the monthly invoice is called "Pegasys 180MCG
10.5ml injection".
After six months we stopped the shots and the following month he
returned for additional tests. The doctor said his test results showed
that the count of virus or bacteria per cubic centimeter had soared
back up to a high level and that the patient needed at least another
year of shots. With tests, consultations and the weekly $270 shots the
cost of treatment is over $1,300 per month or almost $16,000 per year
assuming no further complications, procedures or treatments.
Not one Vietnamese in a 100,000 could afford such an expense so there
must be alternative treatments that are less expensive.
I had a friend diagnosed with another form of hepatitis treated for
two years for the ailment when another doctor figured out that the
problem all along was the result of a gallstone operation during which
pieces of the gallstone had not been properly removed. The new doctor
did a relatively simple procedure to remove the stone particles (not
requiring an operation) and suddenly the so called hepatitis
remarkably diasappeared she was instantly "cured".
Is it possible that a hepatitis C diagnosis could be wrong and that
his man is being treated in a very expensive way for the wrong
disease? How can we be sure the diagnosis is right?
What is this man's long term prognosis with various treatments
including none at all?Hi jack64-ga, and thanks for your question. It seems you and your
friend's husband are in a difficult, expensive situation. As usual,
this is not a substitute for medical advice, evaluation, and
treatment.
First off, the likelihood of being misdiagnosed with Hepatitis C
(provided Western methods were used, as it sounds like they were) is
very small. Table 2 of the source below gives measured sensitivities
and specificities for modern ELISA (Enzyme-Linked Immunosorbent
Assays) for detection of anti-Hepatitis C antibodies in the blood.
You can see this figure here:
http://img133.imageshack.us/img133/8138/ovidwebcgi3ve.jpg
Chou R, Clark EC, Helfand M; U.S. Preventive Services Task Force.
Screening for hepatitis C virus infection: a review of the evidence
for the U.S. Preventive Services Task Force. Ann Intern Med. 2004 Mar
16;140(6):465-79. Review.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15023713&query_hl=1&itool=pubmed_docsum
The free full text of this article can be found fromt the link above.
The most relevant term for thinking about the accuracy of your
friend's diagnosis is the specificity and positive predictive value.
From the above source, the positive predictive value (the chance that
a person with a positive test actually has the disease) for ELISA
ranges from 78-94%. Since it can be as low as 78%, a retest is not a
bad idea. Since your friend has had a second test for re-evaluation
after stopping treatment, and this test was also positive, it is very
likely that he does actually have Hepatitis C. The ELISA test is very
specific (97-99%) for Hep C, and something like gallstones
(cholelithiasis) would not give a false positive test. Such a
condition could lead to elevated liver enzymes, which a relatively
nonspecific indicator of liver disease, which could be caused by
gallbladder disease, liver disease, pancreatic disease, etc. In your
friend's case, he has already had a test that is much more specific
for Hep C, which was positive twice.
================
The reponse to treatment (or no treatment) is summarized nicely in the
above reference:
"Because of the large number of patients and long duration required to
demonstrate improvements in long-term clinical outcomes, intermediate
outcomes have been the most common measure of treatment benefit.
Sustained virologic response rates (absence of viremia 6 months after
completion of a treatment course) are currently considered the best
indication of successful treatment (116).
Antiviral treatment began in 1986 with the use of interferon-[alpha]
(117). Meta-analyses of interferon trials report sustained virologic
response rates of 6% to 21% for interferon monotherapy, compared with
approximately 2% in untreated controls (118-121). Combination
interferon plus ribavirin was approved in 1998 and was found in 3
good-quality systematic reviews to be superior (sustained virologic
response, 33% to 41%) to interferon monotherapy (119-121). Treatment
with pegylated interferon, alone or in combination with ribavirin, has
been used for only a few years. For all interferon-based regimens,
factors associated with successful treatment include genotypes other
than 1, lower baseline viral load, less serious biopsy findings, and
smaller body surface area or lower weight (67)."
The most important indication of successful treatment is the absence
of virus in the blood after treatment has been stopped for 6 months.
Your friend is at the point where he has failed this endpoint and
requires further therapy. What you and he would like to see would be
an effective joust of therapy, after which he could potentially be off
therapy for an extended period.
Pegasys is the trade name for peginterferon-alpha-2a. As suggested
above, this is a relatively new version of the first treatment
modality used against Hep C. Table 3 of the above reference gives a
summary of multiple clinical trials looking at peginterferon-alpha-2a
used with and without ribavirin. You can see Table 3 here:
http://img322.imageshack.us/img322/6851/ovidweb1cgi7if.jpg
As you can see, the most effective therapy was peginterferon-alpha-2a
(Pegasys) plus ribavirin, with a virus-free state achieved in 53-60%
of patients.
"The 2 good-quality trials found that 54% to 56% of all patients
achieved a sustained virologic response with pegylated interferon plus
ribavirin versus 44% to 47% with pegylated interferon monotherapy (P
<= 0.01) (122, 123). One of these trials also found a higher sustained
virologic response rate with pegylated interferon plus ribavirin
compared with nonpegylated interferon plus ribavirin (56% vs. 44%; P <
0.001) (122)."
Table 4 of this article summarizes the recent studies for all of the
treatment regimens, including placebo (no treatment). It also
includes a "number needed to treat," which is useful in thinking about
the numbers for clinicians. It means that a physician would need to
(on average) treat this number of patients with the drug regimen
listed to see a complete virus free response in one patient 6 months
after treatment is stopped. A lower "number needed to treat"
indicates a more effective treatment. An example: If you need to
treat 200 patients before 1 shows a response, this is not a very
effective treatment. If the number is 1 needed to treat, then this is
a perfect treatment.
You can see Table 4 here:
http://img133.imageshack.us/img133/3907/ovidweb2cgi4jh.jpg
__________
The document cited below also summarizes the CDC's current stance on treatment:
"Therapy for hepatitis C is a rapidly changing area of clinical
practice. Combination therapy with interferon and ribavirin, a
nucleoside analogue, is now FDA-approved for treatment of chronic
hepatitis C in patients who have relapsed following interferon
treatment and might be approved soon for patients who have not been
treated previously. Studies of patients treated with a combination of
ribavirin and interferon have demonstrated a substantial increase in
sustained response rates, reaching 40%-50%, compared with response
rates of 15%-25% with interferon alone (139,140). However, as with
interferon alone, combination therapy in patients with genotype 1 is
not as successful, and sustained response rates among these patients
are still less than 30%.
Most patients receiving interferon experience flu-like symptoms early
in treatment, but these symptoms diminish with continued treatment.
Later side effects include fatigue, bone marrow suppression, and
neuropsychiatric effects (e.g., apathy, cognitive changes,
irritability, and depression). Interferon dosage must be reduced in
10%-40% of patients and discontinued in 5% -15% because of severe side
effects. Ribavirin can induce hemolytic anemia and can be problematic
for patients with preexisting anemia, bone marrow suppression, or
renal failure. In these patients, combination therapy should be
avoided or attempts should be made to correct the anemia. Hemolytic
anemia caused by ribavirin also can be life-threatening for patients
with ischemic heart disease or cerebral vascular disease. Ribavirin is
teratogenic, and female patients should avoid becoming pregnant during
therapy.
Other treatments, including corticosteroids, ursodiol, and thymosin,
have not been effective. High iron levels in the liver might reduce
the efficacy of interferon. Use of iron-reduction therapy (phlebotomy
or chelation) in combination with interferon has been studied, but
results have been inconclusive. Because patients are becoming more
interested in alternative therapies (e.g., traditional Chinese
medicine, antioxidants, naturopathy, and homeopathy), physicians
should be prepared to address questions regarding these topics."
==========================================
You can read more about Pegasys here:
http://www.pegasys.com/
http://www.rocheusa.com/products/pegasys/
http://www.rxlist.com/cgi/generic3/pegasys.htm
As you say, Pegasys is expensive:
http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00004035239&trx=1Z5006
This site quotes a price of $1,487.96 for a kit of 4 180mcg vials,
which works out to $371.99, which is even higher than you are paying
now.
The standard treatment is 48 weeks of Pegasys (once per week) plus
ribavirin (aka Copegus) every day. You can read more about ribavirin
here:
http://www.rxlist.com/cgi/generic4/copegus.htm
Ribavirin is taken orally and, unfortunately, is also expensive. Here
are some prices from Drugstore.com:
http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00004008694&trx=1Z5006
To figure out the best dosage for ribavirin, one must determine which
genotype of Hepatitis virus your friend has (1, 2, 3, or 4).
Genotypes 1 and 4 require 48 weeks of therapy, while Genotypes 2 and 3
require 24 weeks. 48 weeks of therapy works out to (1200mg of
ribavirin per day) about 2016 tablets or $16,657.20. You will likely
have somewhat lower pricing in Vietnam, as with Pegasys.
==========================================
In terms of long term outcomes, the above reference again has some
useful information. Table 5 summarizes multiple studies looking at
long term outcome of patients who were untreated, treated with
Interferon-alpha alone, Interferon-beta alone, or only symptomatic
therapy. You can see Table 5 here:
http://img288.imageshack.us/img288/6708/ovidweb3cgi7io.jpg
Another consideration is looking beyond blood viral loads to what
these numbers mean. Table 6 of the above paper shows the differences
in functional status for patients who responded to therapy versus
those who didn't.
http://img304.imageshack.us/img304/5287/ovidweb4cgi0ox.jpg
==========================================
Disease course:
This resource from the CDC summarizes the typical disease course:
Recommendations for Prevention and Control of Hepatitis C Virus (HCV)
Infection and HCV-Related Chronic Disease
http://www.cdc.gov/mmwr/preview/mmwrhtml/00055154.htm
"The course of chronic liver disease is usually insidious, progressing
at a slow rate without symptoms or physical signs in the majority of
patients during the first two or more decades after infection.
Frequently, chronic hepatitis C is not recognized until asymptomatic
persons are identified as HCV-positive during blood-donor screening,
or elevated ALT levels are detected during routine physical
examinations. Most studies have reported that cirrhosis develops in
10%-20% of persons with chronic hepatitis C over a period of 20-30
years, and HCC in 1%-5%, with striking geographic variations in rates
of this disease (124-128). However, when cirrhosis is established, the
rate of development of HCC might be as high as 1%-4%/year. In
contrast, a study of greater than 200 women 17 years after they
received HCV-contaminated Rh factor IG reported that only 2.4% had
evidence of cirrhosis and none had died (129). Thus, longer term
follow-up studies are needed to assess lifetime consequences of
chronic hepatitis C, particularly among those who acquired their
infection at young ages.
Although factors predicting severity of liver disease have not been
well-defined, recent data indicate that increased alcohol intake,
being aged greater than 40 years at infection, and being male are
associated with more severe liver disease (130). In particular, among
persons with alcoholic liver disease and HCV infection, liver disease
progresses more rapidly; among those with cirrhosis, a higher risk for
development of HCC exists (131). Furthermore, even intake of moderate
amounts (greater than 10 g/day) of alcohol in patients with chronic
hepatitis C might enhance disease progression. More severe liver
injury observed in persons with alcoholic liver disease and HCV
infection possibly is attributable to alcohol-induced enhancement of
viral replication or increased susceptibility of cells to viral
injury. In addition, persons who have chronic liver disease are at
increased risk for fulminant hepatitis A (132)."
You can find some other CDC recommendation statements on Hepatitis C here:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/index.htm#recs
You can also find an excellent summary of Hepatitis C diagnosis,
treatment, and disease course at this eMedicine article:
http://www.emedicine.com/med/topic993.htm
==========================================
So, to summarize, the current accepted therapy for Hepatitis C is
Pegasys plus ribaviron for 48 weeks (possibly 24, depending the
specific genotype). Both Pegasys and ribaviron are staggeringly
expensive. Unfortunately, other therapies have not been proven to be
effective. This combination is only effective in about half the
cases. Most people throughout the world probably can't afford this
type of therapy and, sadly, suffer the sequelae of long term chronic
Hepatitis C infection, including cirrhosis (within 20 years in 20% of
patients), liver cancer (1-4% of patients with cirrhosis), and other
less common problems such as lymphoma. Many of these patients
ultimately require liver transplant, also not widely available outside
major western medical centers.
Response to combination therapy can be as high as 60%. Patients who
abstain from alcohol do better.
==========================================
I hope this information is helpful in your difficult decision making
process. I wish you and your friend's husband the best in this.
Please feel free to request any clarification prior to rating.
-welte-gaThanks for your kind words and most generous tip! While the number of
patients who are ultimately virus free is only in the 50-60% range,
this is still better than none given the grave consequences of
untreated Hep C. Also, your friend's husband had a 6 month course of
Pegasys, which is about half what is recommended for 2 of the 4
genotypes of Hep C. It might be worth getting a genotype test to see
if he should have been on a full 48 weeks of therapy. It truly is a
very difficult situation. I hope that it works out for the best.
-welte-ga#If you have any other info about this subject , Please add it free.# |
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