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Dental Problems
| Open Wide - By: Tamra B. Orr |
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| Summary: |
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If you have hepatitis C or any number of liver diseases, your dental
health may be more important than you think |
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| Story: |
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If you have hepatitis C or any number of liver diseases, your dental
health may be more important than you think. In many instances, poor
dental health can result in a patient’s being rejected for transplant.
Even in less dire circumstances, problems with your teeth and gums are
no laughing matter, and the risk of infection is greatly increased. In
other words, you may not need that perfect smile to remain healthy or
ensure your eligibility for transplant, but you should at least be
concerned about maintaining good dental health.
If not,
you should probably take heed the next time a doctor tells you to ...
Open Wide
When you
combine the conditions of hepatitis and dental problems, three issues
tend to surface: the special dental concerns of the hepatitis patient,
the risk of transmission to the dentist – now considered very low – and
the strict dental requirements for the patient who needs a transplant.
All three can cause stress and concern.
To
worry or not to worry
For the
most part, hepatitis patients do not have to worry about dental problems
any more than the average person. “A hepatitis patient has the same
responsibility to his or her teeth as every other citizen out there,”
says Richard Darling, D.D.S. “They simply need to keep their teeth clean
and free of plaque.” One study, published in the Australian Dental
Journal in 2000, said there is some evidence that shows hepatitis
patients are slightly more prone to tooth decay, but it is nothing
serious.
One
problem that may show up in patients, especially those on
antidepressants, is a chronic condition of xerostomia, or dry mouth.
Saliva is much more than just spit. It cleans, lubricates and protects
the teeth. If the amount of saliva in your mouth decreases, it can
adversely affect those very same teeth. “If a patient has a dry mouth,
the chance of dental caries (cavities) climbs,” says Dr. Martin
Greenberg, chairman of the department of the at the . “Saliva protects
the teeth from bacteria. Under management, we sometimes give extra
fluoride treatments.” Besides having a mouth that feels like it is
stuffed with cotton, xerostomia patients may have a sore tongue, gums or
cheeks; frothy or foamy saliva; difficulty talking, eating and
swallowing; bad breath; or sensitive teeth. If the condition persists,
decay can accelerate. Simple help can be found in chewing gum or eating
sugar-free candies, as well as in increasing your fluid intake.
Another
dental complication can come quite indirectly. “One-third of hepatitis
patients on medication suffer depression and, thus, impaired perception
of self-care,” says Darling. “They may take less care of their teeth,
and problems will occur.”
For the
hepatitis patient who is searching for a dentist, it is considered
respectful to let him or her know that you have the condition because it
can potentially affect how he cares for you, what prescriptions he
recommends and so on. “I care for a bunch of heppers and advise them
that it is simply proper courtesy to notify the dental technicians and
dentists about their diagnosis, as it has blood-borne risks. If a
dentist runs away screaming into the wilderness when you tell him you
have hepatitis, he is the wrong doctor for you anyway,” says Dr.
Patricia Raymond, a physician in gastroenterology and general internal
medicine, as well as author of the humorous “Don’t Jettison Medicine”
and “Colonoscopy: It’ll Crack u Up” and host of the popular National
Public Radio show “Housecalls.” “As a physician, I assume you have every
possible infectious disease when you come into my office, and I take
universal precautions.” This doesn’t mean you have to announce the fact
over the phone to the entire front desk, however. “You don’t necessarily
want to have this information stamped across all of your records,” says
Dr. Raymond. “Ask to speak one-on-one with the dentist instead.” Simply
share the information with those who need to know because they will be
exposed.
Letting
the dentist know about your condition is just playing fair. Often he
will ask to see your most current numbers and medical records as well.
He has good reason to be cautious. Although some dentists might be
worried about the risk of contracting the disease from an accidental
needle stick, most of them just need to know the information before they
can safely place you in the chair. For example, if you have a
significant amount of cirrhosis, it can affect how your blood clots – or
doesn’t. After a dental procedure like an extraction, a root canal or
other work, your dentist needs to know if you’re going to have prolonged
bleeding thanks to a lack of
coagulation.
Knowing
what kind of medications you are on is also essential. If you have
severe liver disease, for example, and are taking antibiotics, your
ability to metabolize medications may be altered. Interferon can also
occasionally cause mouth sores, which your dentist also needs to know.
If you have already had a transplant, you will be more susceptible to
several health problems (such as cold sores, herpes and yeast
infections) due to the immunosuppressants you are taking so your body
does not reject the new liver. Before the dentist uses any kind of
anesthesia or analgesic on you for
any procedure, he has to know what you are already taking so he can be
aware of any problems or contraindications. That is simple medical
common sense, and it not only protects him, but certainly protects you
as well.
But
what about me?
It isn’t
unusual for a dentist to be concerned about treating a hepatitis
patient. After all, this is a blood-borne disease, and they work pretty
up close and personal with blood and saliva. In this day and age of
barrier protection, however, that fear should be declining fast.
“Dentists now use universal precautions,” says Dr. Greenberg. “That has
really cut back on the problem. Basically, all patients
are treated as if they have a
contagious disease now. Because of that, transmission is almost unheard
of.”
“I feel that the biggest problem with dental care and hepatitis today is
the lack of education,” says Dr. Bernstein, chief of the combined
Divisions of Gastroenterology, Hepatology and Nutrition at and Long
Island Jewish Medical Center in . “I have many dentists calling me every
week about treating the hepatitis patient. This is a disease that is
misunderstood, and they need this education.” Dr. Bernstein lectures to
dental professionals in his area of about the epidemiology and stages of
hepatitis so that dentists have a better concept of the condition. “It
would be so nice to find a way to educate dentists so they do not have
to keep calling and asking questions,” he says, “but that is a very big
task.”
On the list
If you are on the transplant list, you already know that you have to be
completely free of any dental disease before an operation will occur.
“At the Department of Oral Medicine here at the , we have a service
where all transplant patients get a full dental evaluation,” says Dr.
Greenberg. “We must eliminate any possible oral influences on infection.
While dental problems are not as serious with a liver transplant as they
might be with a bone marrow transplant, for instance, it is still an
important issue.” All transplant centers offer some kind of dental care
for their patients, from the smallest sign of infection to having every
tooth removed.
Hepatitis is a condition that already has enough questions and concerns
not to need any more. When it comes to dental health, the keys are
simply remembering basic hygiene, reporting any anomalies to your
dentist, being honest with him about your condition and treatment and,
if possible, making sure he has the knowledge he needs so he will not be
worried that his health is at risk with you as his patient.
A Personal Perspective
In
the pamphlet “Dental Health and Hepatitis C” from the Australian Society
for HIV Medicine Inc. ( www.ashm.org.au
), one patient recalls his experience with having the disease and his
concerns about going to the dentist.
“I’ve never disclosed that I have hep C to a private dentist, primarily
because I’d be worried about their level of knowledge and their
attitude. Will they make assumptions and value judgments? Will they be
less attentive and less careful? Will they be less likely to repair or
restore my teeth and more likely to just pull a tooth out?
When you’re a patient,
you don’t always know what a treatment decision is based on. I also
worry about confidentiality. Will dental assistants and receptionists,
as well as the dentist, respect my right to privacy? Do they have
enough
knowledge of the disease not to behave in a discriminatory manner?”
A Story of Hope and Help
Making sure you are free of dental disease can be an expensive part of
treatment. Between the expense of that care, plus the astronomical cost
of a liver transplant, it can be daunting, or even impossible. Just ask
Julie Smith. She is in desperate need of a transplant, but first came
the dental care. At age 32, she had such severe periodontal disease that
she had to have all of her teeth removed. It was the more economical
choice. Once her teeth were out, Julie struggled to eat – no easy chore.
That is when dentist Richard Darling of the FAIR Foundation (
www.fairfoundation.org
) heard about her. (The foundation defines itself as “a national
movement to reverse inequities in research funding distributions by the
National Institutes of Health.”) Thanks to his help and the assistance
of another health care provider, Dr. George Hardy, Julie got a
complimentary full set of dentures. “She got them yesterday,” Darling
says. “She was exceptionally happy and said that she felt she had a
normal face again.” As the mother of three young children, this was
especially important to her.
Now
that Julie has found hope, she needs help. Medicaid covers only half of
the $450,000 fee for the transplant, medications and care. Darling is
helping raise the rest of the money for Julie and urges all fellow
physicians, dentists and other caring people to consider contributing
also. You can check out the web site at
www.geocities.com/save_julie /. Darling has reason to hope that the
money will be found. Recently, the foundation raised $1 million to help
another patient get a life-saving heart and liver transplant.
Darling also knows the
desperate need for a liver transplant on a personal level. He has had
three of them due to hepatitis that he contracted from a blood
transfusion years ago. He wrote of his experience with the transplants,
as well as liver cancer, diabetes and a heart attack, in a book called
“Coma Life” (www.comalife.org ). “The whole point of this is
giving Julie hope,” Darling says. |
http://www.hepatitismag.com/storydetail.asp?storyid=143
Hepatitis C and Dental Care
Alan Franciscus,
Editor-in-Chief, HCV Advocate
Poor dental health is
a rising problem among people living with hepatitis C. Hepatitis C is
associated with a wide range of dental problems ranging from dry mouth,
tooth decay, gum infections, tooth sensitivity and mouth infections which
can dramatically affect one’s quality of life.
The majority of
patients with hepatitis C experience periods of having a dry mouth. The
degree of dry mouth can also be made worse with medications that many
patients with hepatitis C are taking including, but not limited to,
anti-depressants and interferon. Saliva plays a key role in lubricating the
mouth and is important in speaking, tasting and chewing the food that we
eat. Saliva can also prevent viruses, fungus and bacteria from causing
infections in our mouths that can lead to tooth decay and gum disease. A
dry mouth in of itself can be frustrating and can be improved by frequently
sipping water, chewing sugarless gum that will stimulate the salivary glands
in your mouth to release saliva or by using a saliva substitute which can be
purchased in your local pharmacy.
As a result of dry
mouth and lack of saliva for protection, patients with hepatitis C need to
be concerned about tooth decay. Tooth decay in the early stages is
reversible so regular dental check-ups are important especially while on HCV
medications. Other things that you can do to prevent tooth decay is to
include good oral hygiene, using a soft toothbrush and fluoride toothpaste.
Also reduce your carbohydrate (sugar) consumption, cut back on your intake
of sweetened foods and beverages high in sugar. Again, chewing sugarless
gum is good as it helps with saliva production and can also neutralize the
acid that causes the tooth decay.
The first sign of a
gum infection is most likely to be bleeding from the gum margin usually as a
result of brushing your teeth, which can increase the risk for
transmission. Other signs which would indicate more advanced gum infection
include swelling and redness of the gums, receding gums, loose teeth, a bad
taste or halitosis (bad breath). The main cause of gum infection is plaque
which is a colorless sticky film of bacteria that forms on the teeth,
produces toxins and causes inflammation. Patients with hepatitis C who are
taking interferon therapy or those with cirrhosis have a much lower
resistance to gum infection than others. In addition, hepatitis C patients
who smoke worsen this gum condition. Gum infection can be reduced with
appropriate thorough tooth brushing with a soft toothbrush angled at 45
degrees to the gum margin, as well as dental floss use. Dental floss should
be passed gently between the teeth and rubbed up and down to the gum
margin.
People with hepatitis
C will sometimes complain of having sensitive teeth. If enamel is lost from
the surface of the tooth or if the root surface is exposed this can cause
sharp pain when exposed to hot or cold extremes. Causes of sensitive teeth
include poor brushing, erosive foods (including lemons, grapefruit, vinegar
and soda) frequent vomiting or gastric reflux and grinding of teeth most
commonly during sleep. There are desensitizing toothpastes on the market as
well as gum guards for people who are prone to grinding their teeth.
As discussed earlier,
patients with hepatitis C often experience dry mouth due to lack of saliva
production. This lack of saliva production can also cause mouth infections
as bacteria, viruses and fungus can flourish, resulting in patients with
hepatitis C being more prone to mouth ulcers and thrush. Thrush is an
overgrowth of a yeast (fungus) called "candida." The medical name for thrush
is candidiasis. In the mouth, thrush looks like creamy white patches or
small red spots on the tongue, roof of the mouth (also called the hard
palate), gums or throat. Crusting on the corners of the mouth is also a
symptom of thrush. Thrush can make it difficult or painful to swallow and
can cause chest pain. It can cause nausea and make your food taste
different. This is further exacerbated when on interferon therapy. Daily
intake of natural yogurt may help with thrush but, if that is not effective,
thrush can be resolved by using a medicine called nystatin.
Copyright 2002
– Hepatitis C Support Project – All Rights Reserved. Permission to reprint
is granted and encouraged with credit to the Hepatitis C Support Project
October 2002
Depression
PSYCHOLOGIC STRESS,
DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH LIVER DISEASE DUE TO
HEPATITIS C VIRUS. N. Singh^{*}, T. Gayowski, M.M. Wagener, I.R. Marino.
Veterans Affairs Medical Center, Pittsburgh, PA. Background: Quality of
life is frequently compromised by chronic illnesses. While numerous studies
have assessed the clinical impact of hepatitis C virus (HCV) hepatitis, the
psychosocial sequelae and quality of life impairment in patients with liver
disease due to HCV is not known. Methods: Depression, psychologic stress and
quality of life was prospectively assessed in 82 liver transplant
candidates. Comparisons were made between patients with HCV hepatitis (n=42)
versus patients with other liver diseases (n=40). Depression was assessed by
Beck Depression Inventory, emotional stress by Profile of Mood States scale
(POMS), coping by Ways of Coping scale, and stressful life events by Recent
Events Inventory. Quality of life measure included a self-assessed rating of
perceived quality of life. Results: Patients with HCV were significantly
younger than all other patients (p=.002). Emotional stress, i.e., total mood
disturbance score (p=.038), tension and anxiety (p = .047) and confusion and
bewilderment (p=.035) were significantly higher in patients with HCV.
Patients with HCV were significantly more depressed as assessed by Beck
Depression Inventory scores (p = .014) and had significantly greater
impairment in Beck inventory items pertaining to somatic manifestations of
depression (perceptions of body images, work inhibition, sleep disturbance,
fatigue, appetite and weight loss, somatic preoccupation) than all other
patients (p = .018). A significantly higher number of patients with HCV
reported experiencing pain (p=.001). There was no difference in coping,
social support, religious support, education, employment, income, Karnofsky
score, Child-Pugh score, or liver function tests between patients with HCV
versus all other patients. Conclusion: Patients with HCV hepatitis are
uniquely vulnerable to depression and psychological stress in the
pretransplant period than all other patients. Symptoms of depression should
be sought in these patients since depression is a treatable and modifiable
disorder.
Hepatitis C virus
infection and incident type 2 diabetes
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Hepatology July 2003, Vol 38, Numb 1
Shruti H. Mehta et al. Departments of 1Epidemiology and
2Medicine, Johns Hopkins University, Baltimore, MD; and the
3Division of Epidemiology, University of Minnesota School of
Public Health, Minneapolis, MN.
"...compared with persons without HCV infection at high risk
for diabetes, those with HCV infection at high risk were
more than 11 times as likely to develop type 2 diabetes
(relative hazard, 11.58; 95% confidence interval, 1.39-96.6;
P value for test of interaction = 0.04)...
a significant increase in the incidence of diabetes was not
detected among anti-HCV-positive persons who were at low
risk for diabetes (relative hazard, 0.48; 95% confidence
interval, 0.05-4.40).." What about the influence of diet,
alcohol and other behavior influences (see below for
Discussion by authors). Based on these preliminary findings
HIV-infected individuals with HCV or perhaps HBV may have
even a greater risk for developing diabetes. What is the
influence of having HCV or HBV on study findings in HIV of a
higher prevalence of diabetes or insulin resistance? I don't
think this has been examined in such studies. Considering
that the HIV Lipodystrophy Workshop takes place next week in
Paris, the publication of this article is good timing.
This is an interesting topic. These study findings are based
on a small number of 15 cases of HCV infection. Although
studies show individuals with HCV are often more likely to
have diabetes, does HCV contribute to development of
diabetes. My feeling is yes for some individuals. And having
predisposition to developing diabetes plus having HCV may
both contribute synergistically. It should be noted that the
risk for developing diabetes is higher among individuals on
HAART (HIV therapy). Two small studies find that HCV/HIV and
HBV/HIV co-infected individuals are at greater risk for
developing insulin resistance and diabetes, as well as
having lipid abnormalities and body changes..
This study did not examine the stage of liver disease as a
factor in developing diabetes. Perhaps having cirrhosis or
more advanced liver disease predisposes individuals to
developing diabetes, as well as lipid abnormalities and
HIV-related body changes. The relationship between HIV, HCV
and HBV, the stage of liver disease, and body changes in
HIV+ individuals has received little research attention.
For individuals with diabetes or a predisposition for
glucose abnormalities, the difficulty in tolerating HCV
therapy may make it more difficult to monitor diet and
glucose levels. After initiating therapy for HCV co-infected
individuals should be particularly careful in monitoring
their diet and glucose levels.
For HCV or HBV mono- or co-infected individuals it appears
reasonable that an impaired liver might play a role in
contributing to changes in metabolism related to fats and
sugar. In order to better understand this question more
in-depth study is important and should be seriously
considered by researchers particularly by researchers
specializing in HIV-lipodystrophy.
The authors of this study said:
"...The present findings suggest that the association
between HCV infection and type 2 diabetes may be stronger
for persons defined as high risk on the basis of their age
and BMI. Although this study suggests a temporal
relationship between HCV infection and type 2 diabetes,
these results should be considered to be of a preliminary
nature due to the low prevalence of HCV infection."
"...In this investigation, the incidence of type 2 diabetes
was increased substantially for persons with recognized
diabetes risk factors and HCV infection compared with those
with similar diabetes risk factors but not HCV
infection...and supports many of the previous
investigations... In addition, the present study extends
this research by showing that HCV infection antedated the
development of type 2 diabetes, providing preliminary
epidemiologic evidence supporting the hypothesis that HCV
infection causes type 2 diabetes. Further studies are needed
to confirm these preliminary findings and to elucidate the
underlying biologic mechanism before causality can be firmly
established... The conclusions that can be made from this
study are limited by the unexpected low prevalence of HCV
infection in this population... With only 15 cases of HCV
infection, it is possible that some cases were highly
influential..... It also was not possible to determine
whether the observed effect modification by age and BMI was
real or caused by random variation. Likewise, it is possible
that no increased risk for diabetes was detected among anti-HCV-positive
persons who were otherwise at low risk because of limited
power.... It also is possible that HCV infection modified
the effect of age and BMI on the risk for diabetes. (see
discussion below)... It also is possible that HCV infection
was a marker for some other risk factor of type 2 diabetes
that was not measured in this population (see discussion
below)
Nearly 4 million persons in the United States and 170
million persons worldwide have been infected with the
hepatitis C virus (HCV). HCV infection primarily causes
liver disease, but also has been linked to other conditions
including type 2 diabetes mellitus. The association between
HCV infection and type 2 diabetes has been clearly shown by
cross-sectional studies that included prevalent cases of
diabetes, but there is insufficient evidence to conclude
that HCV infection causes type 2 diabetes. Although most of
the evidence supports that HCV infection antedates type 2
diabetes, it also is possible that persons with diabetes are
at increased risk for acquiring HCV infection because of
frequent hospital interventions and daily use of syringes.
To ascertain if HCV infection causes type 2 diabetes, the
temporal relationship needs to be established. In a
community-based sample of adults in the United States, we
assessed whether persons with HCV antibodies were at
increased risk for type 2 diabetes. Because previous studies
have suggested that among individuals with HCV infection,
those with diabetes are more likely to have traditional risk
factors of diabetes, we also examined whether this
relationship between HCV infection and type 2 diabetes was
modified by known risk factors of diabetes including age and
obesity.
ABSTRACT-Summary
Although hepatitis C virus (HCV) infection is more common
among adults with type 2 diabetes, it is uncertain whether
HCV precedes the development of diabetes. Thus, we performed
a prospective (case-cohort) analysis to examine if persons
who acquired type 2 diabetes were more likely to have had
antecedent HCV infection when enrolled in a community-based
cohort of men and women between the ages of 44 and 65 in the
United States (Atherosclerosis Risk in Communities Study [ARIC]).
Among 1,084 adults free of diabetes at baseline, 548
developed diabetes over 9 years of follow-up evaluation.
Incident cases of diabetes were identified by using fasting
glucose and medical history and HCV antibodies were assessed
at baseline. A priori, persons were categorized as low-risk
or high-risk for diabetes based on their age and body mass
index, factors that appeared to modify the type 2 diabetes-HCV
infection incidence estimates.
The overall prevalence of HCV in this population was 0.8%.
Among those at high risk for diabetes, persons with HCV
infection were more than 11 times as likely as those without
HCV infection to develop diabetes (relative hazard, 11.58;
95% confidence interval, 1.39-96.6). Among those at low
risk, no increased incidence of diabetes was detected among
HCV-infected persons (relative hazard, 0.48; 95% confidence
interval, 0.05-4.40).
In conclusion, pre-existing HCV infection may increase the
risk for type 2 diabetes in persons with recognized diabetes
risk factors. Additional larger prospective evaluations are
needed to confirm these preliminary findings.
Study population
The Atherosclerosis Risk in Communities (ARIC) study is a
multicenter cohort designed to study the etiology and
natural history of atherosclerosis. The details of the study
design have been published elsewhere. Briefly, between 1987
and 1989, 15,792 men and women aged 45 to 64 were recruited
from 4 communities in the United States-Forsyth County, NC;
Jackson, MI; northwest suburbs of Minneapolis, MN; and
Washington County, MD. At baseline and 3 follow-up visits
(1990-1992, 1993-1995, 1996-1998), subjects underwent an
interview, examination, and blood draw. Written informed
consent was obtained from all participants and a repository
of plasma and serum aliquots from each visit was stored
frozen at -70¡C.
A total of 5,517 (35%) individuals were excluded from this
analysis because of prevalent or missing diabetes status at
baseline (n = 2,018), missing baseline plasma specimens due
to use in other substudies (n = 2,506), missing information
on essential covariates (n = 14), restricted access to
stored specimens (n = 7), race other than African American
or white (n = 95), failure to return for any follow-up (n =
851), and insufficient information to characterize diabetes
in even one follow-up visit (n = 26), leaving 10,275 (65%)
individuals in the sampling frame.
Definition of cases (diabetes)
Fasting serum glucose measurements were performed at each
follow-up visit by using the hexokinase method.16 Incident
cases of diabetes were defined as participants meeting one
of the following criteria at any of 3 follow-up visits: (1)
self-reported use of hypoglycemic medications; (2) fasting
(>8 hours) serum glucose level greater than 7.0 mmol/L (126
mg/dL); (3) nonfasting serum glucose level greater than 11.1
mmol/L (200 mg/dL); or (4) self-report of physician
diagnosis. For individuals classified by physician diagnosis
or medication use, date of diabetes onset was considered to
be the midpoint between the last visit when an individual
was not diabetic and the first visit when an individual was
diabetic. For those diagnosed by fasting or nonfasting
glucose level, date of diabetes onset was the estimated date
at which blood sugar level crossed a threshold (7.0 mmol/L
for fasting and 11.1 mmol/L for nonfasting), assuming a
linear increase in glucose level between visits.
RESULTS
Cases of type 2 diabetes tended to be older, male (43% vs
34%, p=.03), and African American (37% vs 20%, <.0001) when
compared with noncases and the cohort sample.
Persons with type 2 diabetes also tended to have lower
educational attainment, higher BMI (morbidly obese: >35
kg/m2 BMI, 23% vs 6% p=.00004) and were more likely to
report a family history of diabetes than those without type
2 diabetes. Obese (30-35 kg/m2 BMI) individuals trended
towards having diabetes rather than not having diabetes but
it wasn't identified as being significant (27% vs 19%).
Individuals categorized as lean/normal BMI (<25 kg/m2) and
overweight (25-30 kg/m2) trended towards not having diabetes
although this was not significant either. Showing that
keeping weight down helps in preventing diabetes.
Because the cohort sample was sampled to be representative
of the original ARIC cohort, the association between HCV
infection and diabetes risk factors was examined in these
628 persons, of whom 8 (0.8%) were anti-HCV positive.
The prevalence of HCV infection was higher among men than
women (1.5% vs. 0.47%, P = .04) and African Americans than
whites (2.47% vs. 0.3%, P = .03). However, there were no
differences in HCV prevalence by other correlates of type 2
diabetes (e.g., age, BMI, or family history of diabetes).
Overall, persons with HCV infection were nearly twice as
likely as those without HCV infection to develop diabetes,
but this difference was not statistically significant
(relative hazard, 1.9; 95% confidence interval, 0.6-6.2).
After stratification for underlying diabetes risk, a
significant increase in the incidence of diabetes was not
detected among anti-HCV-positive persons who were at low
risk for diabetes (relative hazard, 0.48; 95% confidence
interval, 0.05-4.40). However, compared with persons without
HCV infection at high risk for diabetes, those with HCV
infection at high risk were more than 11 times as likely to
develop type 2 diabetes (relative hazard, 11.58; 95%
confidence interval, 1.39-96.6; P value for test of
interaction = 0.04).
When the analysis was restricted to include only the 12
persons who had ongoing HCV infection, the relationship
between HCV and type 2 diabetes among high-risk persons was
attenuated (relative hazard, 7.61; 95% confidence interval,
0.85-68.4, P = .07).
At baseline, among the 15 individuals with HCV infection,
those who developed diabetes had higher fasting insulin
levels (136 pmol/L; interquartile range [IQR], 108-230 pmol/L)
and more insulin resistance (4.8 pmol/L; IQR, 4.0-9.8) as
measured by the HOMA-IR method (fasting insulin [Uu/mL] ´
fasting glucose [mmol/L]/22.5) compared with those who did
not develop diabetes (72 pmol/L; IQR, 50-176 and 2.5; IQR,
1.5-5.9, respectively), but these differences were not
statistically significant (P = .18 and .13, respectively).
Albumin levels at baseline were significantly lower among
HCV-infected persons who developed diabetes (median, 3.6;
IQR, 3.5-3.9) compared with HCV-infected persons who did not
develop diabetes (median, 4.1; IQR, 4.0-4.2; P = .02), a
result driven by differences in the high-risk group.
However, median platelet counts did not differ between the 2
groups (225 and 210 for persons who did and did not develop
diabetes, respectively, P = .89).
Among all high-risk persons, fasting insulin levels and
insulin resistance were slightly higher in those who were
HCV-infected compared with those who were not, but these
differences were not statistically significant.
However, among persons with a high BMI (>30 kg/m2), median
insulin levels and insulin resistance were significantly
higher among HCV-infected persons compared with HCV-uninfected
persons.
DISCUSSION by authors
In this investigation, the incidence of type 2 diabetes was
increased substantially for persons with recognized diabetes
risk factors and HCV infection compared with those with
similar diabetes risk factors but not HCV infection.
Detection of an increased risk for type 2 diabetes among
those with HCV infection supports many of the previous
investigations that have documented an association between
HCV infection and type 2 diabetes in other settings,
including liver clinics, diabetes clinics, and the general
U.S. population. In addition, the present study extends this
research by showing that HCV infection antedated the
development of type 2 diabetes, providing preliminary
epidemiologic evidence supporting the hypothesis that HCV
infection causes type 2 diabetes. Further studies are needed
to confirm these preliminary findings and to elucidate the
underlying biologic mechanism before causality can be firmly
established.
The conclusions that can be made from this study are limited
by the unexpected low prevalence of HCV infection in this
population. With only 15 cases of HCV infection, it is
possible that some cases were highly influential. However,
in a sensitivity analysis, systematic removal of cases did
not significantly alter the results. Additionally because
the sampling weights varied quite widely, we investigated
the sensitivity of the results to the weights. The hazard
ratios remained large despite reductions in the weights of
up to 50%. When the largest weights were reduced
dramatically (40%), some results were no longer
statistically significant, but this is probably more because
of the small number of cases rather than the weighting
scheme itself. The small number of HCV cases also prohibited
multivariate analysis. Although we indirectly accounted for
age and BMI through the risk group classification, we were
not able to account for other known correlates of diabetes
including race and socioeconomic status. However, in our
previous analysis, adjustment for these factors actually
strengthened the association between HCV infection and type
2 diabetes,13 suggesting that the relative hazard observed
in this study might even be an underestimate of the
relationship between HCV and type 2 diabetes. It also was
not possible to determine whether the observed effect
modification by age and BMI was real or caused by random
variation. Likewise, it is possible that no increased risk
for diabetes was detected among anti-HCV-positive persons
who were otherwise at low risk because of limited power.
Although power calculations performed before the study was
conducted suggested greater than 80% power based on an HCV
prevalence of 1.8% among persons without diabetes (the
average among U.S. adults), post hoc power calculations
based on the observed prevalence of 0.8% revealed only 30%
power to detect in the low-risk stratum a difference of the
same magnitude as was observed in other studies.
It also is possible that HCV infection modified the effect
of age and BMI on the risk for diabetes. This is supported
by the observation that HCV-infected individuals who were
obese (BMI > 30 kg/m2) had significantly higher insulin
levels and insulin resistance at baseline compared with HCV-negative
individuals who also were obese regardless of diabetes
status. In previous studies, HCV-infected persons with
diabetes also were more likely than HCV-infected persons
without diabetes to be older and obese. There are
insufficient data to explain these observations. However, it
is interesting to note that both obesity and older age were
associated with more severe liver disease among HCV-infected
patients.
The link between advanced liver disease and type 2 diabetes
has been suggested by a number of studies. Patients with
cirrhosis are predisposed to insulin resistance and,
consequently, type 2 diabetes. Some studies have shown that
even among HCV-infected persons without type 2 diabetes or
cirrhosis, insulin resistance and glucose intolerance are
present. In these individuals, the degrees of insulin
resistance and glucose intolerance still were related
closely to the severity of liver damage. Steatosis is also a
feature of chronic HCV infection. A recent study suggested
that greater than 60% of persons chronically infected with
HCV had steatosis. In this and other studies, steatosis also
was associated with high BMI and fibrosis. Because steatosis
also has been associated with type 2 diabetes, it may not be
surprising that HCV infection, age, and obesity combined
dramatically increase a person's risk for type 2 diabetes.
Unfortunately, we were not able to address adequately the
role of liver disease because neither liver biopsy specimens
nor markers of severe liver disease including total
bilirubin and prothrombin time were available. Baseline
albumin levels were available and were observed to be
significantly lower among HCV-infected persons who developed
diabetes compared with those who did not develop diabetes.
On the other hand, there were no differences in platelet
counts and none of the 15 HCV-infected persons reported a
history of liver disease or cirrhosis (asked at the third
visit, data not shown).
Further support for the hypothesis that diabetes occurs more
frequently among HCV-infected persons because of advanced
liver disease would come from showing that the hazard of
developing diabetes would be greatest in those with ongoing
HCV infection, which was only observed (positive HCV antigen
and/or RNA) in 12 individuals in this study. The relative
hazard among the high-risk group with ongoing HCV infection
remained elevated but was reduced in magnitude and
statistical significance compared with the relative hazard
for all HCV antibody-positive persons. It is difficult to
speculate on the reasons for this because the precision of
these estimates is very low given that so few people were
HCV-RNA positive. Because the overall number of positives
was already low, because we found essentially the same
estimates in the ongoing infection group, and because we
could not test sera from additional visits to ensure there
was not a problem with sample handling or storage, we chose
to focus our analysis on HCV antibody-positive persons.
It also is possible that HCV infection was a marker for some
other risk factor of type 2 diabetes that was not measured
in this population. HCV infection could be a marker for
ongoing inflammation, which has been associated with the
development of type 2 diabetes. Although plasma fibrinogen
levels were not different among HCV-infected persons who
developed diabetes and those who did not (data not shown),
we did not have information on other markers of inflammation
such as C-reactive protein. It is less likely that HCV
infection was a marker for some other behavioral risk factor
of type 2 diabetes because we had information on most known
risk factors for diabetes including alcohol use and
exercise, neither of which were associated with HCV
infection or the development of type 2 diabetes.
The present findings suggest that the association between
HCV infection and type 2 diabetes may be stronger for
persons defined as high risk on the basis of their age and
BMI. Although this study suggests a temporal relationship
between HCV infection and type 2 diabetes, these results
should be considered to be of a preliminary nature due to
the low prevalence of HCV infection. Larger prospective
studies should include persons at high risk for both HCV
infection and type 2 diabetes to have enough power to firmly
establish a temporal relationship between these 2
conditions.
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Diabetes & Lipids Associated with Liver Disease
Reported by Jules Levin
These studies were reported at the 40th annual EASL liver meeting in Paris
(April 2005). The studies support numerous previous studies that insulin
resistance and diabetes can contribute to advancing liver disease,
particularly in people with viral hepatitis C or B. As well, elevated lipids
may contribute.
Impact of Overweight & Diabetes on Liver-Related Death in Patients with
Alcoholic & Viral Hepatitis C Cirrhosis
G. N'Kontchou1, M. Tin Tin Htar1, J. Paries2, F. Kazemi1, V. Bourcier1, N.
Ganne-Carrie1, P. Nahon1, V. Grando-Lemaire1, J.C. Trinchet1, M. Beaugrand1
1 Liver Unit, Jean Verdier Hospital, Bondy, France 2 Public Health Unit,
Jean Verdier Hospital, Bondy, France
Obesity and diabetes have been suggested to be risk factors of liver-related
death in recent population-based cohort studies. This study was aimed to
assess prospectively the impact of these factors on liver-related death
(including liver transplantation).
Overweight & diabetes type II are risk factors of cirrhosis in patients with
alcoholic & viral HCV. They are also risk factors for liver cancer (hepatocellular
carcinoma). Their influence on liver-related death in patients has not yet
been evaluated.
A large cohoht of 963 patients with compensated cirrhosis regularly followed
for a screening program for HCC were included. All clinical and biological
variables were collected at inclusion. Ultrasonography & alfa-feto protein
were used for follow-up evaluation. Outcomes evaluated were: liver-related
death, liver-related death including liver transplantation (HCC, liver
failure, portal hypertension), & occurrence of HCC was also recorded.
Predictive factors for overall and liver-related death were determined by
log-rank test and Cox proportional hazards model. Survival to events was
estimated by Kaplan-Meier method.
BASELINE CHARACTERISTICS n=963:
Age: 57
63% male
Etiologies: (alcohol/HCV/mixed): 484/322/157
Diabetes: 298 (31%)
BMI (kg/m2): 25/6 +/-4.7
Prothrombine time: 72+/-17
Platelet counts: 137 +/-64
Bilirubin: 28 mmol/l
Albumin (g/l): 39+/-6
AST (N): 2
ALT (N): 2
AP (N): 1.4
y-GT (N): 3.9
Results
-There were 484 alcoholic cirrhosis, 322 HCV, 157 HCV+alcohol.
-Mean age was 57.2±11 yr and mean BMI was 25.6 kg/m2.
-607 were male patients.
-298 patients were diabetic.
-After a mean follow-up of 66.7±45.2 months, 384 patients died, of which 279
were liver-related deaths (liver failure: 142; hepatocellular carcinoma:
117; portal hypertension: 20).
In univariate analysis, factors associated with liver-related death were:
--BMI ³27.5 [OR 1.9; 1.5-2.4; p < 0.0001]
--age >57 yr [OR 1.6; 1.3-2.0; p < 0.0001]
--male sex [1.7; 1.3-2.1; p < 0.0001]
--platelet count <140,000/mm3 [OR 1.9; 1.5-2.5; <0.0001]
--serum albumin <42 g/l [2.8; 2.0-3.9; p < 0.0001]
--prothrombin activity <82% [2.3; 1.7-3.1; p < 0.0001]
--alkaline phosphatase >1.4 ULN [OR 1.9; 1.5-2.4; p < 0.0001]
--total bilirubin >17 mm/ml [OR 1.9; 1.5-2.4, p < 0.0001].
Diabetes was not significantly related.
In multivariate analysis, independent risk factors for liver-related death
were:
--serum albumin <42 g/l [OR 2.00; 1.4-2.9; p = 0.0004]
--BMI ³27.5: [OR 1.8; 1.4-2.4; p < 0.0001]
--age >57 yr [OR 1.7; 1.3-2.3; p = 0.0002]
--male sex [OR 1.5; 1.1-2.1; p = 0.01]
--prothrombin activity <82% [OR 1.6; 1.1-2.2 p = 0.02]
--alkaline phosphatase >1.4 ULN [OR 1.4; 1.0-1.9; p = 0.03].
These results were confirmed in different etiological subgroups.
Conclusion: Overweight was an independent and important predictive
factor of liver-related death in patients with compensated HCV and alcohol
cirrhosis.
Diabetes is Strongly Associated with Advanced Fibrosis; Elevated Lipids
May Be Associated with Fibrosis --Patient Populations with High prevalence
of Diabetes, like Hispanics, May Be Particularly At Risk for Advancing Liver
Disease
"ASSOCIATION BETWEEN DIABETES, OVERWEIGHT, OBESITY AND DYSLIPIDEMIA WITH
FIBROSIS PROGRESSION IN CHRONIC HEPATITIS C PATIENTS"
A. Loaeza-del Castillo, F. Vargas-Vorackova
1 Department of Gastroenterology, Instituto Nacional de Ciencias MŽdicas y
Nutrici—n, Mexico
2 Department of Gastroenterology, Instituto Nacional de Ciencias MŽdicas y
Nutrici—n, Mexico
Fibrosis progression in chronic hepatitis C (CHC) patients is variable,
factors associated with an accelerated progression have been identified, but
they do not account for the heterogeneity seen between individuals.
Aim: To determine the prevalence of diabetes, overweight, obesity and
dyslipidemia in CHC patients and the association of these metabolic factors
with liver fibrosis progression.
Method: Patients with CHC seen in our institution between 1993 and
2003 were retrospectively studied (n = 1618). Patients with a known duration
of infection acquired by transfusion with a liver biopsy performed before
any antiviral treatment were included. Patients with overt hepatic
insufficiency were excluded. The diagnoses of diabetes, overweight, obesity
and dyslipidemia were investigated and liver fibrosis stage (METAVIR).
Variables were tested for their association with significant fibrosis (F2,
F3, F4).
RESULTS
--108 patients were included, 71 (66%) female and 37 (34%) male,
--mean age was 48.7+12.2 years.
--Age at infection was 24.7±13 years, acquired between 1944-2000.
--78% were HCV-genotype 1.
--Fibrosis stage was: F0 = 15 (14%), F1 = 38 (35%), F2 = 9 (8%), F3 = 8 (8%)
and F4 = 38 (35%).
--Mean fibrosis progression rate was 0.106±0.101 (0-0.44).
--26 patients (24%) had diabetes, 10 (9%) glucose intolerance, 24 (22%)
obesity [body mass index (BMI) ³30 kg/m2] and 49 (45%) overweight (25 £ BMI
< 30 kg/m2). --Dyslipidemia was investigated in 75 patients and confirmed in
25 (33.3%). Association between these variables and fibrosis is depicted in
the table.
Conclusions: Diabetes is a factor strongly associated with
advanced fibrosis and cirrhosis. In populations with a high prevalence of
diabetes, such as Hispanics, this association must be taken into account.
Lipid metabolism has a specific role in the pathogenesis of CHC and the
possible protector role of dyslipidemia for significant liver fibrosis
should be investigated in further studies.
"INSULIN RESISTANCE PROMOTES FIBROSIS PROGRESSION AND PREDICTS NECRO-INFLAMMATORY
ACTIVITY IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE"
D. Sanchez-Munoz1, E. Suarez1, M.V. Galan1, L. Grande1, G. Munoz2, M.
Romero-G—mez1
1 Hepatology Unit, Hospital Universitario de Valme, Sevilla, Spain 2
Pathology Unit, Hospital Universitario de Valme, Sevilla, Spain
Aims: To assess the presence of metabolic syndrome X (MSx) and
insulin resistance (IR), and its relationship with histologic damage, in
patients with non-alcoholic fatty liver disease (NAFLD).
Patients and Methods: Thirty-five patients, 25 male and 10 female,
with an average age of 45.7±12.7 [24-76] years, diagnosed by NAFLD, were
included. Liver biopsy was carried out after persistence for, at least, six
months of altered liver enzymes with appropriate diet and physical activity
therapies. Histological damage was assessed according to Brunt criteria (Semin
Liver Dis 2001; 21: 3-16). Body mass index (BMI) was calculated. MSx was
diagnosed according to ATP III criteria. IR was calculated using the HOMA-IR
index = [Glucose(mmol/l) _ Insulin(UI/ml)]/22.5.
RESULTS
Only one patient (2.5%) showed normal weight; 17/35 (48.6%) patients showed
overweight and 17/35 (48.6%) patients were obese.
--MSx was present in 14/35 (42.5%) patients;
--central obesity in 65.7%,
--high triglyceride levels in 62.9%,
--altered glucose metabolism in 28.6%,
--hypertension in 31.4% and
--low HDL-colesterol levels in 24%.
--IR was present (HOMA-IR >2) in 23/33 (74.3%) patients.
--The histologic diagnosis was simple hepatocyte steatosis (HS) in 8/35
(22.9%) patients and steatohepatitis (NASH) in 27/35 (77.1%) patients:
Fibrosis degree was: absent in 13 patients, mild fibrosis (F1-F2) in 6
patients, bridging fibrosis (F3) in 7 patients and cirrhosis (F4) in 1
patient.
Patients with HS showed lower triglyceride levels (99±43 vs 169±85 mg/dl; p
= 0.034) and HOMA-IR (2.54±0.9 vs 4.5±2.5; p = 0.002) than patients with
NASH.
Triglycerides >180 mg/dl or HOMA IR >4.5 was associated with NASH
(Specificity: 100% and Sensitivity: 54.3%.
Fibrosis correlated with age (r = 0.37; p = 0.027), AST (r = 0.5; p =
0.002), and HOMA-IR (r = 0.45; p = 0.007).
In multiple lineal regression, the only factor associated with fibrosis was
the HOMA-IR (R = 0.60; p = 0.0001). All of the patients with advanced
fibrosis (F3-F4) showed a HOMA-IR index >4.5, but only 8/26 (30%) patients
with F0-F2; p < 0.001.
Conclusions: Insulin resistance is present in the majority of the
patients with non-alcoholic fatty liver disease. HOMA-IR index >4.5 or
triglyceride levels >180 mg/dl are predictors of the presence of NASH.
Insulin resistance may play a role in the pathogenesis of fibrosis
progression in patients with NAFLD. Drugs able to decrease insulin
resistance could be useful in the therapy of this disease.
Total Calories May Contribute to Development of Fatty Liver
"LIVER STEATOSIS (Fatty Liver) IN OPEN POPULATION: PREVALENCE AND
RELATIONSHIP TO THE DIET. PRELIMINARY RESULTS OF THE "ARSITA-ONE" PROJECT"
I. Petridis1, E. Lattanzi1, B. Marraccini1, I. Carderi1, E. Claar1, C.
Liani1, S. Lobello1, O. Di Andrea2, M. Chiaramonte1
1 Hepato-Gastroenterology and Nutrition Unit - Dept. of Internal Medicine
and Public Health - L'Aquila University, L'Aquila, Italy 2 Arsita Family
Doctor, Italy
Background and Aim: This study, part of a larger epidemiological
study for liver and metabolic diseases carried out on Arsita (Abruzzo) (805
adult registered inhabitants), was designed: 1) to assess the prevalence of
liver steatosis; 2) to evaluate the relationship with the diet.
Materials and Methods: All subjects aged over 18 yr were invited to
have liver ultrasound (US) and an alimentary questionnaire computer analyzed
(Winfood 1.5). Liver steatosis was classified as none, mild, moderate and
severe. Diet was classified as: diet 1, a traditional local diet,
hypercaloric (3500-4500 kcal), hyperlipidic (55% of calories); diet 2,
similar but with less calories (2500-3500 kcal); diet 3, classic
Mediterranean (2000-2500 kcal).
RESULTS
--541 subjects (253 M and 288 F), completed the US and diet study.
--Moderate/severe steatosis was found in 89/253 (35%) males and 75/288 (26%)
females; in 41/164 (25%) subjects under 40 yr, in 63/119 (33%) subjects aged
40-59 yrs and in 92/196 (47%) subjects over 60 yr.
--143/253 males (57.5%) and 86/288 females (30%) followed diet 1, which was
related to obesity (BMI > 30) in 61% of males and 69% of females, while 14%
of subjects having diet 2 were obese.
--All subjects with mediterranean diet had normal BMI.
--In diet 1 group, 71.5% of males and 64.5% of females had steatosis, while
in diet 2 this was respectively 25.1% and 31.3%.
--In subjects with steatosis, alcohol consumption was present in 82% of
males and in 48% of females, while BMI > 30 was present in 61% of males and
78% of females.
--Out of 164 subjects with steatosis 22 (13%) had altered AST and/or ALT (13
anti-HCV+).
Conclusions: Prevalence of steatosis is increasing with age and is
more frequent in males. In females severe steatosis is mainly correlated
with overweight and in males with alcohol abuse. The amount of total
calories instead of the proportion of fat seems to be related to liver
steatosis. Elderly people had moderate/severe in 47%, however in most
cases steatosis is indolent. Hepato cytolisis, without virus, seems to be
very rare. Liver steatosis without "a second hit" seems to be a benign
condition.
Association Between Diabetes, Overweight, Obesity, and Dyslipidemia with
Fibrosis Progression in Chronic Hepatitis C Patients
Fibrosis progression in
chronic hepatitis C (CHC) patients is variable. Factors associated with an
accelerated progression have been identified, but they do not account for
the heterogeneity seen between individuals. The purpose of the present study
was to determine the prevalence of diabetes, overweight, obesity and
dyslipidemia in CHC patients and the association of these metabolic factors
with
liver fibrosis progression.
Patients with CHC seen
in a medical center in Spain between 1993 and 2003 were retrospectively
studied (n=1618). Patients with a known duration of infection acquired by
transfusion with a
liver biopsy performed before any antiviral treatment were
included. Patients with overt hepatic insufficiency were excluded.
Results
·
108 patients
were included, 71 (66%) female and 37 (34%) male, mean age was 48.7 + 12.2
years.
·
Age at infection was 24.7 +/- 13 years, acquired between
1944-2000. 78% were HCV-genotype 1.
·
Fibrosis
stage was: F0=15 (14%), F1=38 (35%), F2=9 (8%), F3=8 (8%) and F4=38 (35%).
·
Mean
fibrosis progression rate was 0.106 +/- 0.101 (0 – 0.44).
·
26 patients
(24%) had
diabetes, 10 (9%)
glucose intolerance, 24 (22%)
obesity (body mass index (BMI) >/= 30 kg/m2) and 49 (45%)
overweight (BMI >/= 25 < 30 kg/m2).
·
Dyslipidemia
was investigated in 75 patients and confirmed in 25 (33.3%).
Association between these
variables and fibrosis is depicted in the table below.
Conclusions
In conclusion the authors
write, “Diabetes is a factor strongly associated with advanced fibrosis and
cirrhosis. In populations with a high prevalence of diabetes,
such as Hispanics, this association must be taken into account.”
“Lipid metabolism has a
specific role in the pathogenesis of CHC and the possible
protector role of
dyslipidemia for significant liver fibrosis should be
investigated in further studies. “
05/04/05
Reference
A
Loaeza-del Castillo and others.
ASSOCIATION BETWEEN
DIABETES, OVERWEIGHT, OBESITY AND DYSLIPIDEMIA WITH FIBROSIS PROGRESSION IN
CHRONIC HEPATITIS C PATIENTS. Abstract 581. 40th EASL. April 13-17, 2005.
Paris, France.
Type II Diabetes
Disease Associations (HCV); Hepatitis C May Be a Cause of Diabetes
Hepatitis Weekly via Individual Inc.
Hepatitis C virus may have a
direct role in the development of diabetes, according to a report from
Spain. Researcher Rafael Simo and colleagues found a high prevalence of
hepatitis C virus (HCV) infection in patients with diabetes, and found that
most HCV patients presented with abnormal liver function tests. "Testing for
HCV infection of diabetic patients with an abnormal liver function test is
mandatory," Simo et al. wrote ("High Prevalence of HCV Infection in Diabetic
Patients," Diabetes Care, September 1996;19(9):998- 1001). "The lack of any
particular epidemiological factor for HCV infection in our diabetic
population suggests that HCV may have a direct role in the development of
diabetes." Mild asymptomatic elevations of serum aminotransferases in a
diabetic patient do not receive much attention because they are often
attributed to fatty infiltration. It has been hypothesized that, during the
course of the disease, diabetic patients are more prone to acquire an HCV
infection because they are subjected to more frequent medical interventions.
While a link between diabetes and HCV has recently been suggested, a
controlled study of prevalence and risk factors for HCV infection has not
yet been performed.
"The aim of this study was to evaluate the prevalence of HCV infection in
diabetic patients attending our outpatient clinic in comparison with blood
donors who were matched for the main risk factors associated with anti-HCV
seropositivity," Simo et al. wrote. "Furthermore, we investigated the
influence of several epidemiological and clinical factors on HCV infection
in diabetic patients, including type of diabetes, duration of the disease,
mode of therapy, and presence of late complications." A total of 176
consecutive diabetic patients were compared with 6172 blood donors, matched
by recognized risk factors to acquire HCV infection. Serologic testing for
anti-HCV was done using a second-generation commercial enzyme-linked
immunosorbent assay (ELISA), and an immunoblot assay was performed in anti-HCV
positive samples to confirm HCV specificity. Diabetic patients were divided
into two groups according to their HCV antibody status and analyzed for age,
sex, type of diabetes, duration of disease, mode of therapy, late diabetic
complications, previous blood transfusion, intravenous drug addiction,
hospital admissions, major surgical procedures, and liver function tests.
Anti-HCV was detected in 18 diabetic patients and 156 blood donors (11.5
versus 2.5 percent; P < 0.001). The estimated risk for HCV infection in
diabetic patients was 4.39 times higher (95 percent CI 2.61-7.24) than in
the control group. In addition, Simo et al. did not observe a significant
difference for previous blood transfusion (21.8 versus 16.7 percent) and
intravenous drug addiction (10.2 versus 5.5 percent) between blood donors
and diabetic patients with HCV infection, respectively. Only age (63.8 +/-
10.2 versus 49.4 +/- 17.8 years) and previous blood transfusion (16.7 versus
1.2 percent; P < 0.05) were statistically related to HCV infection. After
excluding the three anti-HCV positive diabetic patients with previous blood
transfusion, the global prevalence of anti-HCV seropositivity in the
diabetic population (15 of 175, or 8 percent) remained significant in
comparison with the control group (P < 0.001; odds ratio 3.59; 95 percent CI
2.04-6.23).
Furthermore, the three anti-HCV positive diabetic patients with previous
blood transfusion were transfused for unrelated diseases seven, 15, and 23
years before diagnosis of diabetes. In anti-HCV positive diabetic patients,
abnormal liver function tests were seen in 72.3 percent, compared with only
24.7 percent of anti-HCV negative diabetic patients (P < 0.001). "Diabetic
patients have a high prevalence of abnormal liver function tests that are
often attributed to fatty infiltration without further investigation," Simo
et al. wrote. "In this study, we have demonstrated for the first time that
diabetic patients present a higher prevalence of HCV infection than control
subjects who are matched for the main risk factors, such as age, previous
blood transfusion, and intravenous drug addition. In addition, most of anti-HCV
positive patients presented with an abnormal liver function test, being a
combination pattern of cytolysis and cholestasis as the predominant
biochemical alteration. We feel that this is an important point, since none
of these patients had been previously diagnosed with liver disease, and
diabetes was the only reason for referral to our unit. In consequence, based
on our results, testing for HCV infection in diabetic patients with an
abnormal liver function test is mandatory."
The authors suggest their results could be interpreted to mean either
that diabetic patients have some undiscovered epidemiological factor that
increases the risk of acquiring HCV infection or that HCV infection may have
some etiopathogenic role in the development of diabetes. In recent studies
Allison et al. reported a significantly increased rate of diabetes in
patients with HCV related cirrhosis, compared with other causes, and
suggested that HCV infection has some etiopathogenic role in the development
of diabetes (J Hepatol 1994;21:1135-1139). "Several possible mechanisms can
be postulated to link HCV to diabetes," Simo et al. wrote. "It may be
possible that HCV, similar to the hepatitis B virus, could infect pancreatic
islet cells and thereby induce damage to (alpha)-cells. On the other hand,
HCV has been related to diseases in which the autoimmune phenomena play an
important role, such as cyroglobulinemia, glomerulonephritis, thyroiditis,
and Sjogren disease. Therefore, an autoimmune destruction of endocrine
pancreatic tissue related to HCV antigens or immunocomplexes cannot be
excluded."
The corresponding author for this study is Rafael Simo,
Department of Endocrinology, Hospital General Universitari Vall d'Hebron,
Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
HCV and Diabetes Although the association is poorly understood,
there appears to be a connection between HCV and diabetes. A recent study
reported that people with diabetes had four-times the rate of HCV infection
than controls, who were comprised of blood donors. In this study, 11.5
percent of 176 patients with diabetes (type I and II) tested positive for
HCV antibodies, compared to 2.5 percent of 6,172 blood donors.. Another
study reported that of 100 patients with cirrhosis, 34 had HCV infection. Of
those, 17 (50 percent) had concurrent diabetes. Of the 66 HCV-free patients,
only six (9 percent) had concurrent diabetes. Additional studies
substantiate that diabetes is more prevalent in people with HCV infection
than in people with other liver diseases – even when a family medical
history and other risk factors for diabetes are considered.
Sources: "Methods of Transmission of Hepatitis C," C.J. Tibbs, J Viral
Hepat, 1995; 2(3), pp. 113-9.
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