Impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes.

What We Know

Achieving Sustained Virologic Response (SVR) in patients treated with direct-acting antivirals (DAAs) is associated with the reversal of fibrosis, reduces the risk of liver transplant, liver cancer, and risk of other complications of chronic liver disease, including extrahepatic manifestations of HCV. The hepatitis C virus is associated with various extrahepatic manifesations, some of these include systemic manifestations such as thyroid disease, cardiovascular disease, renal disease, eye disease (sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas, and type II diabetes mellitus. As for the latter, previous research has demonstrated a significant association between hepatitis C - type 2 diabetes - and insulin resistance.

The Stats

According to The World Health Organization (WHO) people infected with HCV are at risk for liver related complications, worldwide around 399 000 people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.

Extrahepatic Consequences of HCV
However, because these estimates do not included extrahepatic consequences of HCV infection the risks of morbidity and mortality are underestimated, according to a systematic review investigating the relationship between HCV infection and glucose abnormalities; Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review, published in World J Gastroenterol.

New In The Journals
Learn more about the impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes by viewing this collection of recent articles.

Journal of Medical Virology

Volume 90, Issue 2 February 2018 Pages 320–327

RESEARCH ARTICLE

Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents

Authors Alessia Ciancio, Roberta Bosio, Simona Bo, Marianna Pellegrini, Marco Sacco, Edoardo Vogliotti, Giulia Fassio, Andrea G. F. Bianco Mauthe Degerfeld, Monica Gallo, Chiara Giordanino, Lodovico Terzi di Bergamo, Davide Ribaldone, Elisabetta Bugianesi, Antonina Smedile, Mario Rizzetto, Giorgio Maria Saracco

First published: 14 November 2017

Full publication history DOI: 10.1002/jmv.24954

Abstract

Many studies showed insulin resistance amelioration in HCV-patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct-acting antivirals (DAAs) in HCV-patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P <  0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV-patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long-term.

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Journal of Gastroenterology and Hepatology

HCV clearance by direct-acting antiviral treatments reverses insulin resistance in chronic hepatitis C patients

Luigi E Adinolfi,Riccardo Nevola,Barbara Guerrera,Giovanni D’Alterio,Aldo Marrone,Mauro Giordano, Luca Rinaldi

Accepted manuscript online: 11 December 2017

DOI: 10.1111/jgh.14067

Abstract Background and Aim

Chronic hepatitis C (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. We evaluated the impact of HCV clearance by all-oral direct-acting antiviral (DAAs) treatments on IR and glycemic control.

Methods

Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty-eight treated with DAAs and 65 untreated. Liver fibrosis was assessed by transient elastography. Pre-, end- and 3 months post-treatment withdrawal IR homeostasis was assessed by HOMA-IR, QUICKI and HOMA-B.

Results

At baseline, treated and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90±4.62 and 4.64±5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and BMI, a reduction in HOMA-IR at 2.42±1.85 was showed (p<0.001), in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of SVR patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strict associated with HCV clearance, however, patients with the highest levels of fibrosis remain associated with some degree of IR.

Conclusions

The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.

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Diabetes Care

Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus

Diabetes Care 2017 Sep - Justine Hum,1 Janice H. Jou,1 Pamela K. Green,2 Kristin Berry,2 James Lundblad,3 Barbara D. Hettinger,3 Michael Chang,1 and George N. Ioannou2,4 1Division of Gastroenterology, Portland Veterans Affairs Medical Center, Portland, OR 2Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA 3Division of Endocrinology, Portland Veterans Affairs Medical Center, Portland, OR 4Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA

Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes.

In summary, glycemic control improves in patients with diabetes after DAA-induced SVR. Patients not only have an improvement in HbA1c level after achieving SVR, they are also less likely to require insulin. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes. ....hepatitis C virus (HCV) infection is associated with a higher prevalence of type 2 diabetes mellitus (T2DM) . In addition, HCV proteins increase the release of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which then upregulate gluconeogenesis and enhance lipid accumulation in the liver

Future studies are needed to confirm our findings, to determine how durable the SVR-induced improvement in glycemic control is over time, and to assess the long-term effect on complications of diabetes such as nephropathy, neuropathy, and cardiovascular disease.

View Full Text Article: Available at NATAP

Medpage Today

Commentary: Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus

Direct-acting Hepatitis C Antiviral Treatment in Patients with T2D

Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes

By Kristin Bundy

Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes (T2D). Previous data demonstrated that the risk of developing T2D is about 4 times higher in people infected with the hepatitis C virus (HCV) than those without. Investigators wanted to know: Could HCV suppression lead to better control of T2D?

Continue reading: Available at Medpage Today

Nature - Scientific Reports

Hepatitis B and C virus infection and diabetes mellitus: A cohort study

Yun Soo Hong, Yoosoo Chang, Seungho Ryu, Miguel Cainzos-Achirica, Min-Jung Kwon, Yiyi Zhang, Yuni Choi, Jiin Ahn, Sanjay Rampal, Di Zhao, Roberto Pastor-Barriuso, Mariana Lazo, Hocheol Shin, Juhee Cho & Eliseo Guallar

doi:10.1038/s41598-017-04206-6

Published online:04 2017

In conclusion, in this large study of men and women at low risk of diabetes, we found that serologic evidence of HBV and HCV infection was associated with the prevalence of diabetes. In addition, HBV infection was associated with the risk of incident diabetes in prospective analyses, but we could not reliably evaluate the prospective association between HCV infection and diabetes due to the small number of infected participants. Our studies add to the growing body of evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

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