2. HCV – Diabetes
mellitus relationship
By
Prof. Ahmed Ali Gomaa
Head of Tropical Medicine Department
Fayoum University
3. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
4. Viral hepatitis is the most common cause of liver disease
worldwide.
Hepatitis C virus (HCV) infection is one of the main
causes of chronic liver disease worldwide.
5. The number of chronically infected persons
worldwide is estimated to be about 185 million,
but most are unaware of their infection.
The long-term impact of HCV infection is
highly variable, ranging from minimal
histological changes to extensive fibrosis and
cirrhosis with or without hepatocellular
carcinoma (HCC).
9. Since the discovery of HCV in 1989, interferon
α (IFNα)-based therapy has been the only
treatment , with overall SVR from 50% to 80%
according to HCV genotype, However, the
treatment uptake has been generally low due
to:
- Numerous side effects
- long duration of therapy
- High cost ,and
- Contraindications to IFN based regimens
10. Genotype 2 or 3 Genotype 1 or 4
Ribavirin 800 mg + PEG
Interferon* 180mg a2a or
1.5mg. kg, a2b /w, 24 w.
Ribavirin 1000-1200 mg +
PEG Interferon 180mg a2a or
1.5mg. kg, a2b /w 48 w.
(Traditional HCV therapy)
SVR ~ 80% SVR~50%
12. Treatment
Options
Recommendation status: Regimen Comments by authors
Option 1 B1: PR + SOF 12 wks „appears the most efficacious and the
easiest to use “
Evaluated in TN Neutrino SVR 96% 27/28
No data in TE
Option 2 B1: PR+ SMV 12 wks + additional PR for either
12 or 36 wks
(12 wks SMV + PR; 24 wks total duration for TN & relapsers
including cirrhosis and 48 wks for Prior partials and nulls
including those with cirrhosis)
TN: SVR 89% 31/35
Prior Relapsers: SVR 86% 19/22
Non Responders 57% 41/72
Option 3 B1: PR + DAC 60mg 24 wks
B2: 12 wks TT + additional PR for either 12 or
36 wks: (24 wks total duration for TN & relapsers including
cirrhosis and 48 wks for Prior partials and nulls including those
with cirrhosis)
Theoretically effective, few data available
SVR 100% in 12/12 COMMAND 1 trial
Option 4
IFN intolerant or
ineligible
C2:R + SOF 24 wks „only preliminary data is available in
Egyptian pts“
TN 12 wks treatment: SVR 79% 11/14
TN 24 wks treatment: SVR 100% 14/14
TE 12 wks treatment: SVR 59% 10/17
TE 24 wks treatment: SVR 93% 14/15
Option 5 B2: SOF+SMV 12 wks
Consider adding RBV in patients with predictors of poor response or
in pts with cirrhosis
„no data with this combination- it is likely that
data from Cosmos can be extrapolated“
Option 6 B2: SOF +DAC (60mg) 12 wks TN or 24wks TE
Consider adding RBV in patients with predictors of poor
„no data with this combination- it is likely that
data can be extrapolated“
13. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
14. The liver plays an important role in the
regulation of glucose homeostasis. This helps
explain why glucose intolerance is a feature
or complication of chronic liver disease and
cirrhosis
15. Association between cirrhosis and impaired
glucose metabolism
Up to 96% of patients with cirrhosis have
diabetes or glucose intolerance (Hickman IJ, &
Macdonald GA, 2007).
It occurs in the absence of standard risk
factors of type 2 diabetes such as age, body
mass index and family history of diabetes
(Holstein, etal 2002).
16. The investigators noted that there is
increasing evidence of a link between HCV
and DM.
As the atherosclerosis risk in communities
(ARIC) study reported that HCV infected
individuals who were at risk for DM were 11
times more likely than those without HCV to
develop overt DM
17. Another study noted that the prevalence of
HCV antibodies in diabetics were 4.39 folds
higher than in nondiabetics .
More over , a study involved 1117 HCV and
HBV patient , showed that the prevalence of
DM was 21% in HCV patients and 12% in HBV
patients
18. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
19. HCV infection has been suspected to affect
glucose metabolism and predispose to insulin
resistance ( IR ) and type 2 DM this may be
due to
Direct pancreatic Beta cell destruction
Autoimmune Beta cell injury
Intracellular oxidative stress.
Dysregulation of cytokines
Inhibition of insulin downstream signaling.
Reduce expression of glucose transporters
20. DM affects HCV patients by inducing
Steatohepatitis which accelerate progression
of liver diseases
IR with or without overt manifestations of DM
adversely impact the clinical outcomes in HCV
infected patients in terms of poor response to
antiviral therapy , accelerated progression of
liver fibrosis , and increased risk of HCC
21. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
22. Control of DM associated with good response
to traditional HCV treatment and reduce its
complications
23. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
24. Patients with HCV and DM had improved
cardiovascular and renal outcomes when
treated by antiviral therapy
Researchers analyised 1411 patients with
both HCV and DM who received anti viral
therapy (traditional therapy ) in comparison
with the same number of patients who did
not received antiviral therapy and 5644
diabetics without HCV infections
25. All patients were followed up for 8 years .
Results of the analysis revealed that, patients
with both HCV and diabetes who received
antiviral therapy, there was
1.1% incidence rate of end-stage kidney
disease .
stroke incidence rate of 3.1% .
Heart attack incidence rate of 4.1%.
26. Patients with both diabetes and HCV who
were untreated had incidence rates for kidney
disease, stroke and heart attack of 9.3%, 5.3%
and 6.6% respectively,
while patients with diabetes who did not
have HCV had a 3.3% incidence rate for
kidney disease, 6.1% for stroke and 7.4% for
heart attack.
27. They concluded that :
HCV may cause clinical complications related
to diabetes. But these issues are mitigated by
HCV antiviral therapy, specifically pegylated
interferon plus ribavirin, which was found to
reduce risks of kidney disease, stroke and
cardiovascular diseases in diabetic patients."
28. Introduction of HCV
Role of liver in glucose metabolism
link between HCV and DM.
Effect of control of DM on outcome of HCV
Effect of antiviral therapy on outcome of DM
Conclusion.
29. The liver plays an important role in glucose
homeostasis
There is increasing evidence of a link
between HCV and DM.
Traditional anti viral therapy improves DM
outcomes , such as risk of Heart attack ,
stroke and renal diseases However DAAs
needs more reaches to prove its efficacy .
Control of DM associated with good response
to traditional HCV treatment and reduce its
complications .
30. New era of antiviral therapy (DAAs) showing
excellent SVR in HCV eradication( SVR more
than 90% ) However its role in reducing
diabetic complications needs more and more
studies to be proved .
