HCV – Diabetes mellitus relationship

By

Prof. Ahmed Ali GomaaHead of Tropical Medicine Department

Fayoum University

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.

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.

The number of chronically infected personsworldwide is estimated to be about 185 million,but most are unaware of their infection.

The long-term impact of HCV infection ishighly variable, ranging from minimalhistological changes to extensive fibrosis andcirrhosis with or without hepatocellularcarcinoma (HCC).

Global distribution of HCV genotypesSource: WHO Hepatitis C Fact Sheet (July 2012):

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

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%

Protease inhibitorsBoceprevirTelaprevirSimeprivir

NS5Ainhibitor

(Daclatasvir)

RNA polymerase

inhibitor (Sofosbuvir)

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 4IFN 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 TEConsider adding RBV in patients with predictors of poor

response or in pts with cirrhosis

„no data with this combination- it is likely that

data can be extrapolated“

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.

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

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).

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

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

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.

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

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

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.

Control of DM associated with good response

to traditional HCV treatment and reduce its

complications

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.

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 5644diabetics without HCV infections

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%.

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.

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."

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.

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 .

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 .

Thank you