Interferonlambda and therapy forchronic hepatitis C virus infection

Hepatitis is a medical condition defined by 1.the inflammation of the liver and

2.the presence of inflammatory cells in the tissue of the organ.

The condition can be self-limiting (healing on its own) or can progress to fibrosis (scarring) and cirrhosis.

Hepatitis may occur with limited or no symptoms, but often leads to

jaundice, anorexia and malaise.

Hepatitis is acute when it lasts less than six months and chronic when it persists longer.

AcuteInitial features are of nonspecific flu-like symptoms,

common to almost all acute viral infections and may include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea, and headache.

More specific symptoms are: profound loss of appetite ,dark urine, yellowing of the eyes and skin (i.e., jaundice) and abdominal discomfort.

Physical findings are usually minimal lymphadenopathy (enlarged lymph nodes, in 5%) or splenomegaly (enlargement of the spleen, in 5%).

Signs and symptoms

• Acute viral hepatitis is more likely to be asymptomatic in younger people.

Symptomatic individuals may present after convalescent stage of 7 to 10 days.

• A small proportion of people with acute hepatitis progress to acute liver failure, in which the liver is unable to clear harmful substances from the circulation and produce blood proteins (leading to peripheral edema and bleeding). This may become life-threatening and occasionally requires a liver transplant.

• Chronic hepatitis often leads to nonspecific symptoms such as malaise, tiredness and weakness, and often leads to no symptoms at all.

It is commonly identified on blood tests. The occurrence of jaundice indicates advanced liver damage.

Chronic

• Extensive damage and scarring of liver (i.e. cirrhosis) leads to weight loss, easy bruising and bleeding tendencies, peripheral edema and accumulation of ascites.

• Eventually, cirrhosis may lead to various complications: esophageal varices , hepatic encephalopathy (confusion and coma) and hepatorenal syndrome (kidney dysfunction).

AcuteViral hepatitis: ◦ Hepatitis A, B, C, D, and E.◦ Yellow fever◦ adenoviruses◦ Parvovirus B19

Auto immune conditions, e.g., systemic lupus erythematosus (SLE)

Causes

Chronic Viral hepatitis: Hepatitis B

with or without hepatitis D, hepatitis C (neither hepatitis A nor hepatitis E causes chronic hepatitis)

Autoimmune ◦ Autoimmune hepatitis

Alcohol Drugs ◦ methyldopa◦ nitrofurantoin◦ isoniazid◦ ketoconazole

• Autoimmune• Anomalous presentation of human leukocyte

antigen (HLA) class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection; causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis.

treatment

Some types of hepatitis, such as acute viral forms like hepatitis A and sometimes hepatitis B are self-limited diseases which means that your body's immune system will eventually be able to destroy the viruses that caused the disease.

Goals of Antiviral Therapy that reduce HBV replication are expected to

limit progressive liver disease and improve the natural history of chronic HBV infection.

• Doctors often combine different antiviral drugs to better combat the virus. For example, interferon treatment may often be combined with other antiviral drugs like Lamivudine in the case of hepatitis B infection or Ribavirin for people with hepatitis C infection.

• The drug combinations have a stronger therapeutic effect than a singular drug on its own.

• other antiviral drugs ,Similar to interferon, the side effects can be severe. However, the costs of this combination therapy are relatively reasonable.

• Sometimes hepatitis has developed into such a serious disease that a liver transplant is the only treatment left. This is a complex surgical procedure that involves replacing a failing liver with a donor liver. Thousands of these operations are done every year but because there are many risks involved, it is a treatment of last resort.

Liver Transplantation

• Currently, taking a combination of two drugs, peginterferon and ribavirin, is the standard treatment for chronic hepatitis C.

• This therapy, though not perfect, has the best record of success in reaching SVR among all the drugs known to treat the virus.

• Since these drugs work to stimulate your immune system to fight the virus, some people have better results from them than others do.

Hepatitis C Treatment

SVR is the closest you'll get to "a cure" for hepatitis. Sustained virologic response, or SVR, is the goal of hepatitis C treatment.

Conventional treatment (a combination of interferon and ribavirin) doesn't necessarily eliminate the hepatitis C virus from your liver.

It can, however, suppress the virus to undetectable levels for an extended period of time.

In clinical language, this is called a "sustained virologic response," or sustained response. It means that during the six months after you complete treatment, there is no detectable hepatitis C virus in your blood.

Treatment by interferon

• IFNs are characterized in large part by their ability to induce antiviral activity in receptor-bearing target cells.

• IFNs are divided into type I, II and III subtypes, based in part on the differential use of unique receptors through which they mediate signal transduction.

Interferon (IFN) subtypes

• The type-III subset of the IFN family includes three members: IFN-λ1, -λ2and-λ3 ,also known as IL-29,IL-28A and IL-28B, respectively.

• Here,when referring to type-III IFNs, we use the gene symbols IL29, IL28A and IL28B,but the IFN- λ designations when referring to the corresponding proteins to emphasize their antiviral functions.

• The IFN-λ proteins share common structural features with the IL-10-related cytokines, particularly IL-22; however, unlike IFN-λ, IL-22 does not induce antiviral activity in IL-22-receptor-positive target cells.

• Phylogenetically, IL28A, IL28B and IL29 reside somewhere between the type-I IFNand IL-10 gene families.

Organization and transcriptional regulation of the IFN-λ

genes

• As shown in Figure 1, IL28A, IL28B and IL29 are clustered together on chromosome 19 The exon–intron structure of the IFN-λ genes is similar to the organization of the genes encoding the IL-10-related cytokines.

• the promoters for the IL28A and IL28B genes are very similar, and share several transcriptional regulatory elements in common with the IL29 promoter,suggesting that all three genes are co-regulated in a similar manner.