The Hepatitis/Diabetes Connection

Hepatitis — inflammation of the liver — often can be intertwined with Type 2 diabetes. Although hepatitis can be related to drug and alcohol use, its most common cause in the United States is viral. Moreover, its relationship with Type 2 is reciprocal — the liver disease can cause or worsen diabetes, and diabetes can cause or worsen the severity of inflammation and scarring in the liver.

Three strains of hepatitis virus

Three major strains of hepatitis are seen most often in the U.S. Hepatitis A virus (HAV) usually is spread by close contact with an infected person, but also can be transmitted through exposure to contaminated food or drinking water. According to Mayo Clinic, people with this strain most often recover completely with no damage to the liver.

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Hepatitis B virus (HBV) can be transmitted by contact with blood or other body fluids. HBV is spread through having unprotected sex with an infected person, sharing needles or “works” when shooting drugs, exposure to needle sticks or sharps on the job, or from an infected mother to her baby during birth. Although rare, transmission of the virus has been seen in diabetes patient who share blood glucose monitoring supplies.

Hepatitis C virus (HCV) also is spread through exposure to bodily fluids following most of the same paths as HBV. It is less likely to be transmitted through sexual contact.

HCV is the most common chronic form of the disease. The Centers for Disease Control and Prevention (CDC) reports between 2.7 million and 3.9 million people in the U.S. have chronic HCV (lasting more than six months). In 2014, an estimated 30,500 new cases of acute hepatitis C virus infections were reported in the U.S. Of these, 85% will progress to chronic disease.

A hepatitis C infection can result in long-term health problems. It is the leading cause of scarring in the liver (cirrhosis) and liver cancer, and it is the number one reason for liver transplantation in the U.S. According to the CDC, unlike HAV and HBV, there is no vaccine available to prevent the disease.

Making the connection

“The connection between HCV and Type 2 diabetes seems to be specific in that the incidence of Type 2 is more closely related to HCV than other types of liver disease,” said Mandana Khalili, MD, professor of medicine at the University of California San Francisco and chief of clinical hepatology at San Francisco General Hospital.

Studies have looked at large numbers of people with risk factors for diabetes, such as obesity and age. Those with HCV infections and risk factors were 10 times more likely to develop diabetes than those with the same risk factors who were HCV negative.

“These suggest that potentially, HCV can increase the incidence of Type 2 diabetes in predisposed individuals,” said Khalili. “We think this relationship is related to the virus worsening insulin resistance, one of the mechanisms seen in the development of Type 2 diabetes.”

HBV vaccination lowers diabetes risk

Hepatitis B virus also has been studied in relationship to the risk of developing Type 2 diabetes. However, the reasons for this are not as well understood. The good news is that an analysis of the National Health and Nutrition Examination Survey indicated that people vaccinated for hepatitis B had a 50% reduction in risk for diabetes compared to those not vaccinated. The reduced risk continued even after adjusting for Type 2 diabetes risk factors such as age, obesity, and smoking, according to City of Hope National Medical Center in California.

The CDC and Advisory Committee on Immunization Practices (ACIP) guidelines call for hepatitis B vaccination for all unvaccinated adults with diabetes who are under age 60. For those age 60 and older, talk to your doctor about whether the vaccine is right for your specific circumstances. Currently, there is no vaccine available for HCV.

An HCV infection can result in diabetes control problems for both those newly diagnosed and people who have been treated successfully. Even those who have been stabilized for long periods of time can see their glucose control thrown off by the increases in insulin resistance.

Increased risk of fatty liver disease

Another major concern in both hepatitis and diabetes is fatty deposits in the liver leading to scarring. The two together seem to have an additive effect, making non-alcoholic fatty liver disease (NAFLD) even more likely and often more serious.

“The epidemic of prediabetes, diabetes, and obesity increases the chances of having nonalcoholic steatohepatitis (NASH) even before HCV is factored in,” said Kenneth Cusi, MD, chief of the division of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville. “Roughly two out of every three people who are obese or have Type 2 diabetes have too much fat in their livers. Of these, one-third develop inflammation in the liver from NASH.”

Over time, this results in scarring and cirrhosis of the liver—one of the reasons HCV is the number one cause of liver transplants, with 40% of the total related to this disease.

“Having diabetes is bad for those with fatty liver disease,” said Khalili. “Type 2 diabetes speeds up the progression of liver disease and scarring when present. The chances of liver cancer also increase in this group.”

HCV has five identified sub-strains or genotypes. The exact genotype a person has may have an impact on both diabetes and fatty liver diseases. Genotype 1 is seen in the largest proportion of individuals with HCV. Type 2 diabetes is more prevalent in these patients, probably because of increased insulin resistance.

Treatment options for HCV

Genotype 3 is harder to treat and can result in more fat in the liver. This higher incidence of fatty liver disease increases the importance of managing diabetes aggressively to lessen or eliminate another risk factor for fatty liver.

When discussing treatment options for HCV, two goals should be kept in mind. The first is to achieve what doctors call “sustained eradication of HCV,” defined as the absence of any trace of the virus in blood tests six months or more after completing antiviral medications. The second is to prevent cirrhosis, liver cancer, or end-stage liver disease requiring liver transplantation.

Just within the last few years, major advances in the treatment of HCV have led to a cure. In the past, treatment was a long and confusing process involving multiple drugs with multiple side effects.

For many years, the treatment of choice was pegylated interferon and ribavirin, with the possible addition of boceprevir (Victrelis™, from Merck) and telaprevir (Incivek™, from Vertex) for HCV genotype 1 infection. The medications were given for 24 to 48 weeks and successfully cured HCV in 50% and 80% of patients. (Both have discontinued sales in the U.S. because of treatment advances.)

In 2013, two new direct acting antiviral drugs — Sofosbuvir (Sovaldi™, from Gilead) and Simeprevir (Olysio™, from Janssen) — were approved to treat chronic HCV infection. They had the advantage of needing only 12 to 14 weeks of treatment. Cures were seen in 80% to 95% of patients, according to the CDC.

Harvoni™ (from Gilead) followed in late 2014. This combination drug is a once-daily pill that has cured more than 90% of patients with HCV genotype 1 after 12 weeks of treatment. Some patients have been cured as soon as after eight weeks of treatment.

Since then, additional drugs have been approved for HCV therapy, including Viekara Pak™ (from AbbVie, ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets), Daklinza™ (daclatasvir, from Bristol-Myers Squibb) to be used in combination with Sovaldi, and Zepatier™ (elbasvir/grazoprevir combination therapy, from Merck). Even more drugs are anticipated in the near future.

Which medications you will be prescribed will depend on many factors and will be tailored to your specific case. Some medications have been shown to work better than others for specific genotypes. You may be taking medications for some medical problem in addition to those for Type 2 and HCV that could interact with the usual hepatitis medications. These newer drugs can be very expensive, so insurance coverage and financial concerns may affect on your options.

Transplantation is another possible treatment for HCV, particularly among those whose cirrhosis has advanced. As with any surgery, control of blood sugars prior to the operation is an important consideration, although having diabetes is not considered a reason to cancel a transplant.

“Having a transplant does make it more of a challenge to control diabetes,” said Cusi. “The immunosuppression drugs used to stop rejection worsen insulin resistance, and glucose becomes more difficult to control. The ideal would be for the person to lose weight and get the diabetes optimally controlled prior to transplant.”

New treatment for NASH

A recent study suggests pioglitazone (Actos™, from Takeda), a Type 2 medication, also may have an impact on NASH and fatty liver disease. Published in the Annals of Internal Medicine, research by Cusi and others looked at 101 patients with prediabetes or Type 2 and NASH confirmed by biopsy. After being assigned to a weight-reduction diet, they were given either the main drug or placebo for 18 months. Then all were given pioglitazone for an additional 18 months.

“Of those on medication, 58% of the patients saw improved NASH disease activity scores,” said Cusi. “This is the first time that we have a possible long-term treatment for those with either prediabetes or Type 2 and NASH.”

The impact of medical advances

Although medications can cure HCV in the vast majority of patients, how this will affect Type 2 diabetes has not yet been identified.

“It is not yet very clear as to whether successful treatment of the HCV will help resolve the diabetes,” said Kahlili. “Treatment does seem to improve insulin resistance, and while it is a risk factor, not everyone with insulin resistance goes on to develop diabetes. Treating the diabetes also helps lessen the progression of liver disease in HCV, so it is very important to appropriately treat Type 2 in those with HCV.”

Advances in understanding and treating both HCV and NASH have driven changes that may result in lessening the impact of liver disease on diabetes and the impact of diabetes on NASH and other fatty liver disease complications.

“I think this is a great time for treatments in HCV and Type 2,” said Cusi. “The treatments for viral hepatitis are the best in history. There is now a generic medication with a 50% to 60% chance of reversing the inflammation from fatty liver disease induced by obesity or Type 2 diabetes and probably preventing end-stage liver disease. This is a very promising time for patients.”