Prevalence of Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with and without Interferon and Ribavirin
Mostafa Abdul Mogheeth Mohamed Allam;
Abstract
The human liver is the largest single organ in the body and consists of parenchymal cells, which metabolize, detoxify, synthesize, and store nutrients.
Hepatitis C is a disease with a significant global impact. According to the World Health Organization there are 170 million people infected with the hepatitis C virus (HCV), corresponding to 3% of the world’s total population. There are considerable regional differences. In some countries, e.g., Egypt, the prevalence is as high as 20%.
Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. It is estimated that 170 million persons in the world are infected with HCV with a global prevalence of about 3%. Every year there are estimates of 3 to 4 million new cases of infection due to transfusion contamination, contaminated injection needles, and parenteral exposure.
The number of patients actually HCV RNA positive is estimate to be around 80 to 90% of all HCV-antibody positive persons. Certain groups are preferentially affected: The highest risk factor in most instances is injection drug use. But patients undergoing hemodialysis and persons who received blood transfusions before 1991 are at risk also.
Acute HCV infection is diagnosed when there is circumstantial evidence of new infection (such as recent exposure to a known HCV-infected inmate) or the presence of clinical features of acute hepatitis (jaundice, nausea, anorexia, and malaise), and where the other causes of hepatitis have been excluded. Acute hepatitis C rarely causes fulminant hepatic failure. However, super-infected persons who also have underlying chronic hepatitis B infection are at greater risk for severe hepatitis.
The mean incubation period, from transmission of HCV infection to the onset of symptoms is 6–7 weeks, however, only 20–30% of newly infected persons are actually symptomatic. Serum Alanine Aminotransferase (ALT) levels increase 4–12 weeks after acute HCV infection. HCV RNA is detectable in serum within days to 8 weeks following infection. Antibodies to HCV (anti-HCV) are detectable 3 months after infection in 90% of patients.
The risk of chronic HCV infection is high. About 75% of patients with acute hepatitis C do not eliminate HCV RNA and progress to chronic infection.
Most patients with chronic infection are asymptomatic or have only mild nonspecific symptoms as long as cirrhosis is not present. The most frequent complaint is fatigue. Less common manifestations are nausea, weakness, myalgia, arthralgia, and weight loss. Aminotransferase levels can vary considerably over the natural history of chronic hepatitis C.
The diagnosis of chronic HCV infection is based on the detection of HCV RNA by a sensitive molecular method (lower limit of detection <15 international units [IU]/ml). Anti-HCV antibodies are detectable by enzyme immunoassay (EIA) in the vast majority of patients with HCV infection but EIA results may be negative in early acute hepatitis C and in profoundly immunosuppressed patients.
The goal of therapy is to slow progression of fibro¬sis and prevent the development of cirrhosis, thereby helping patients live longer, symptom-free lives.
Standard therapy for the treatment of chronic HCV infection is pegylated interferon and ribavirin. Oral ribavirin monotherapy is not effective for inducing sustained virologic response. A recent randomized controlled trial compared pegylated interferon alfa-2b plus ribavirin with pegylated interferon alfa-2a plus ribavirin and found no statistical difference for sustained virologic response. The duration of therapy is determined by HCV geno¬type and virologic response to therapy. In general, patients with genotypes 1 and 4 are treated for 48 weeks, and those with genotypes 2 and 3 are treated for 24 weeks. Other interferons (consensus interferon and albinter¬feron alfa-2b) and ribavirin alternatives (taribavirin) are being developed to improve the effectiveness, safety, and tolerability of therapy for chronic HCV infection.
In addition to pegylated IFN-α and ribavirin, three new hepatitis C virus direct acting antivirals (DDAs) licenced in the EU in the first half of 2014, for use as part of combination therapies for HCV infection. Sofosbuvir, a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, has been approved in January 2014. Simeprevir, a second-wave, first generation NS3/4A protease inhibitor will be approved in May 2014. Daclatasvir, an NS5A inhibitor, is likely to be approved in August or September 2014. Other drugs may be approved later in 2014 or in 2015 and an update of these guidelines will be provided when this is the case.
HCV can leads to insulin resistance (IR), fibrosis, liver cirrhosis, steatosis and hepatocellular carcinoma (HCC) in a substantial number of patients.
While the liver is the primary organ affected by chronic hepatitis C virus (HCV), a broad clinical spectrum of extrahepatic complications and diseases are associated with this viral infection.
The most well characterized of the extrahepatic manifestations are include mixed cryoglobulinemia, non- Hodgkin’s lymphoma (NHL), cutaneous vasculitis, glomerulonephritis, neuropathy, lymphoproliferative disorders (LPDs), and other less common manifestations.
Thyroid disorders related to chronic hepatitis C infection untreated with pegylated interferon and ribavirin:
A spectrum of clinical thyroid disorders may be observed in patients with HCV including hypothyroidism, hyperthyroidism (Grave’s disease), Hashimoto’s thyroiditis, and the presence of antithyroid autoantibodies in the absence of overt thyroid disease. Patients with chronic HCV have also been found to have a higher prevalence of papillary thyroid carcinoma.
The risk of developing thyroid function disorders concerns women (they have a four times higher risk than men) and patients with thyroid peroxidase antibodies found before the treatment (46.1% vs. 5.4%).
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. In the United States and other areas of adequate iodine intake, autoimmune thyroid disease (Hashimoto disease) is the most common cause of hypothyroidism; worldwide, iodine deficiency remains the foremost cause. Symptoms like weight gain, slowed speech, dry skin, hair loss of scalp, axillary or pubic hair coarse features, goiter and pitting edema. Untreated cases may lead to myxedema coma or even death. Treatment is thyroid hormone and treatment of the cause.
Hashimoto thyroiditis is characterized by the destruction of thyroid cells by various cells and antibody mediated immune process. It is a part of the spectrum of autoimmune thyroid disease. Finding include: pyffy face, periorbital edema, bradycardia and elevated blood pressure. The treatment of choice is thyroid hormone replacement. The drug of choice is orally adiminstered levothyroxine usually for life.
Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to the hypermetabolic condition of thyrotoxicosis. The most common forms of hyperthyroidism include diffuse toxic goiter (Grave’s disease). Finding include: nervousness, anxiety, hyperactivity, tachycardia, hands tremors and weight loss. Treatment of hyperthyroidism includes symptom relief, as well as therapy with antithyroid medications, radioactive iodine-131 (I131), or thyroidectomy.
The antithyroid antibodies may persist in CHC patients after cessation of IFN therapy. The incidence of autoantibodies in CHC patients with or without IFN treatment is reported to be 10-45 %. Patients undergoing interferon and ribavirin combination therapy develop autoimmune hypothyroidism more often than patients receiving interferon monotherapy.
The incidence of thyroid dysfunction in chronic hepatitis C patients was investi¬gated and it was identified that the percentage of patients with liver disorder was highest in those with hypothyroidism (69%) than in other types of TD. A correlation between hypothyroidism and liver disorders may exist in HCV infected patients. However, as patients with chronic thyroiditis compli¬cated with hypothyroidism show a lower percentage of liver disorders than those with hypothyroidism, the higher inci-dence of liver disorder in patients with hypothyroidism may be unrelated to autoimmune disorder.
Hepatitis C is a disease with a significant global impact. According to the World Health Organization there are 170 million people infected with the hepatitis C virus (HCV), corresponding to 3% of the world’s total population. There are considerable regional differences. In some countries, e.g., Egypt, the prevalence is as high as 20%.
Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. It is estimated that 170 million persons in the world are infected with HCV with a global prevalence of about 3%. Every year there are estimates of 3 to 4 million new cases of infection due to transfusion contamination, contaminated injection needles, and parenteral exposure.
The number of patients actually HCV RNA positive is estimate to be around 80 to 90% of all HCV-antibody positive persons. Certain groups are preferentially affected: The highest risk factor in most instances is injection drug use. But patients undergoing hemodialysis and persons who received blood transfusions before 1991 are at risk also.
Acute HCV infection is diagnosed when there is circumstantial evidence of new infection (such as recent exposure to a known HCV-infected inmate) or the presence of clinical features of acute hepatitis (jaundice, nausea, anorexia, and malaise), and where the other causes of hepatitis have been excluded. Acute hepatitis C rarely causes fulminant hepatic failure. However, super-infected persons who also have underlying chronic hepatitis B infection are at greater risk for severe hepatitis.
The mean incubation period, from transmission of HCV infection to the onset of symptoms is 6–7 weeks, however, only 20–30% of newly infected persons are actually symptomatic. Serum Alanine Aminotransferase (ALT) levels increase 4–12 weeks after acute HCV infection. HCV RNA is detectable in serum within days to 8 weeks following infection. Antibodies to HCV (anti-HCV) are detectable 3 months after infection in 90% of patients.
The risk of chronic HCV infection is high. About 75% of patients with acute hepatitis C do not eliminate HCV RNA and progress to chronic infection.
Most patients with chronic infection are asymptomatic or have only mild nonspecific symptoms as long as cirrhosis is not present. The most frequent complaint is fatigue. Less common manifestations are nausea, weakness, myalgia, arthralgia, and weight loss. Aminotransferase levels can vary considerably over the natural history of chronic hepatitis C.
The diagnosis of chronic HCV infection is based on the detection of HCV RNA by a sensitive molecular method (lower limit of detection <15 international units [IU]/ml). Anti-HCV antibodies are detectable by enzyme immunoassay (EIA) in the vast majority of patients with HCV infection but EIA results may be negative in early acute hepatitis C and in profoundly immunosuppressed patients.
The goal of therapy is to slow progression of fibro¬sis and prevent the development of cirrhosis, thereby helping patients live longer, symptom-free lives.
Standard therapy for the treatment of chronic HCV infection is pegylated interferon and ribavirin. Oral ribavirin monotherapy is not effective for inducing sustained virologic response. A recent randomized controlled trial compared pegylated interferon alfa-2b plus ribavirin with pegylated interferon alfa-2a plus ribavirin and found no statistical difference for sustained virologic response. The duration of therapy is determined by HCV geno¬type and virologic response to therapy. In general, patients with genotypes 1 and 4 are treated for 48 weeks, and those with genotypes 2 and 3 are treated for 24 weeks. Other interferons (consensus interferon and albinter¬feron alfa-2b) and ribavirin alternatives (taribavirin) are being developed to improve the effectiveness, safety, and tolerability of therapy for chronic HCV infection.
In addition to pegylated IFN-α and ribavirin, three new hepatitis C virus direct acting antivirals (DDAs) licenced in the EU in the first half of 2014, for use as part of combination therapies for HCV infection. Sofosbuvir, a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, has been approved in January 2014. Simeprevir, a second-wave, first generation NS3/4A protease inhibitor will be approved in May 2014. Daclatasvir, an NS5A inhibitor, is likely to be approved in August or September 2014. Other drugs may be approved later in 2014 or in 2015 and an update of these guidelines will be provided when this is the case.
HCV can leads to insulin resistance (IR), fibrosis, liver cirrhosis, steatosis and hepatocellular carcinoma (HCC) in a substantial number of patients.
While the liver is the primary organ affected by chronic hepatitis C virus (HCV), a broad clinical spectrum of extrahepatic complications and diseases are associated with this viral infection.
The most well characterized of the extrahepatic manifestations are include mixed cryoglobulinemia, non- Hodgkin’s lymphoma (NHL), cutaneous vasculitis, glomerulonephritis, neuropathy, lymphoproliferative disorders (LPDs), and other less common manifestations.
Thyroid disorders related to chronic hepatitis C infection untreated with pegylated interferon and ribavirin:
A spectrum of clinical thyroid disorders may be observed in patients with HCV including hypothyroidism, hyperthyroidism (Grave’s disease), Hashimoto’s thyroiditis, and the presence of antithyroid autoantibodies in the absence of overt thyroid disease. Patients with chronic HCV have also been found to have a higher prevalence of papillary thyroid carcinoma.
The risk of developing thyroid function disorders concerns women (they have a four times higher risk than men) and patients with thyroid peroxidase antibodies found before the treatment (46.1% vs. 5.4%).
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. In the United States and other areas of adequate iodine intake, autoimmune thyroid disease (Hashimoto disease) is the most common cause of hypothyroidism; worldwide, iodine deficiency remains the foremost cause. Symptoms like weight gain, slowed speech, dry skin, hair loss of scalp, axillary or pubic hair coarse features, goiter and pitting edema. Untreated cases may lead to myxedema coma or even death. Treatment is thyroid hormone and treatment of the cause.
Hashimoto thyroiditis is characterized by the destruction of thyroid cells by various cells and antibody mediated immune process. It is a part of the spectrum of autoimmune thyroid disease. Finding include: pyffy face, periorbital edema, bradycardia and elevated blood pressure. The treatment of choice is thyroid hormone replacement. The drug of choice is orally adiminstered levothyroxine usually for life.
Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to the hypermetabolic condition of thyrotoxicosis. The most common forms of hyperthyroidism include diffuse toxic goiter (Grave’s disease). Finding include: nervousness, anxiety, hyperactivity, tachycardia, hands tremors and weight loss. Treatment of hyperthyroidism includes symptom relief, as well as therapy with antithyroid medications, radioactive iodine-131 (I131), or thyroidectomy.
The antithyroid antibodies may persist in CHC patients after cessation of IFN therapy. The incidence of autoantibodies in CHC patients with or without IFN treatment is reported to be 10-45 %. Patients undergoing interferon and ribavirin combination therapy develop autoimmune hypothyroidism more often than patients receiving interferon monotherapy.
The incidence of thyroid dysfunction in chronic hepatitis C patients was investi¬gated and it was identified that the percentage of patients with liver disorder was highest in those with hypothyroidism (69%) than in other types of TD. A correlation between hypothyroidism and liver disorders may exist in HCV infected patients. However, as patients with chronic thyroiditis compli¬cated with hypothyroidism show a lower percentage of liver disorders than those with hypothyroidism, the higher inci-dence of liver disorder in patients with hypothyroidism may be unrelated to autoimmune disorder.
Other data
| Title | Prevalence of Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with and without Interferon and Ribavirin | Other Titles | مدى إنتشارالإختلال الوظيفي للغدة الدرقية في مرضى الإلتهاب الكبدي المزمن بفيروس سي المعالجون وغير المعالجون بالأنترفيرون و الريبافيرين | Authors | Mostafa Abdul Mogheeth Mohamed Allam | Issue Date | 2014 |
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