Hepatitis C medical therapy

Overview

Treatment

Acute Hepatitis C

Since the majority of patients with acute hepatitis C are asymptomatic, the infection often goes unnoticed until the effects of chronic hepatitis begin to manifest. It is usually rare to closely monitor patients at risk to detect the development of acute hepatitis C. In the majority of patients, the response rate to treatment is higher in the acute rather than the chronic phase of infection. Moreover, treating patients with acute hepatitis has consistently shown high rates of viral clearance and significantly lower rates of chronicity. However, the best treatment regimen, the time of initiation, and the duration of therapy is still debatable. If a patient is identified as having an acute hepatitis C infection, the initial approach would include a period of monitoring of 8 - 20 weeks (often 8 - 12 weeks) to detect spontaneous viral clearance. New data suggests higher rates of viral clearance in untreated patients with acute clinical hepatitis C than previously reported.For patients who fail to clear the infection spontaneously, treatment should be initiated with Peg-IFN alfa ± ribavirin for 24 to 48 weeks, based on HCV genotype and response to therapy determined by HCV RNA measurement. Revised AASLD guidelines for the management of acute hepatitis C are expected in the summer of 2014.

Chronic Hepatitis C

Approach & Pre-treatment Assessment

Several key points need to be addressed in patients with chronic Hepatitis C prior to the initiation of therapy. Every patient with documented infection requires evaluation to determine if he/she qualifies for medical therapy. Patients with clear indications for treatment require an extensive pre-treatment assessment. Important considerations include HCV genotype, extent of liver disease, concomitant alcohol abuse, psychiatric disorders, and pregnancy among others. With current regimens being physically and financially demanding, screening is essential to identify patients requiring therapy.

Pretreatment Assessment in Patients with Chronic Hepatitis C

Necessary
Complete medical history, with emphasis on complications of liver disease, significant extrahepatic disease, and symptoms of chronic HCV that affect quality of life Psychiatric history including past or ongoing disorders with screening for depression and alcohol use Serum HBsAg, antiHBc, antiHBs, antiHAV Quantitative HCV RNA measurement HCV genotype Previous antiviral therapies and response Serum ALT, serum albumin, serum bilirubin (including direct bilirubin), and prothrombin time CBCD TSH Creatinine Glucose Uric acid (receiving telaprevir) Ferritin, iron saturation, and serum ANA Pregnancy test HIV serology ECG in patients with known cardiac disease
Recommended
Liver biopsy only if results will influence management IL28B genotype only if results will influence management Urine toxicology screen for opiates, cocaine, and amphetamines Eye exam for retinopathy in patients with diabetes or hypertension

Treatment Indications & Contraindications

Treatment accepted for patients with following characteristics: (should fulfill all characteristics)

• Age ≥ 18 years
• HCV RNA positive
• Liver biopsy showing chronic hepatitis with bridging fibrosis or higher
• Compensated liver disease:
  • Total bilirubin = 1.5 g/dL
  • INR = 1.5
  • Serum albumin > 3.4
  • Platelet count = 75,000 mm
  • No evidence of hepatic decompensation (hepatic encephalopathy or ascites)
• Acceptable hematological and biochemical profile:
  • Hemoglobin = 13 g/dL for men; 12 g/dL for women
  • Neutrophil count = 1500 /mm3
  • Serum creatinine = 1.5 mg/dL
• Willing to adhere to therapy
• No contraindications to therapy

Treatment contraindicated for patients with any of the following characteristics:

Adverse Effects

Interferon therapy

Most persons have flu-like symptoms (fever, chills, headache, muscle and joint aches, fast heart rate) early in treatment, but these lessen with continued treatment. Later side effects may include tiredness, hair loss, low blood count, trouble with thinking, moodiness, and depression. Severe side effects are rare (seen in less than 2 out of 100 persons). These include thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection. Although rare, deaths have occurred due to liver failure or blood infection, mostly in persons with cirrhosis. An important side effect of interferon is worsening of liver disease with treatment, which can be severe and even fatal. Interferon dosage must be reduced in up to 40 out of 100 persons because of severity of side effects, and treatment must be stopped in up to 15 out of 100 persons. Pregnant women should not be treated with interferon.

Combination (ribavirin + interferon) treatment

In addition to the side effects due to interferon described above, ribavirin can cause serious anemia (low red blood cell count) and can be a serious problem for persons with conditions that cause anemia, such as kidney failure. In these persons, combination therapy should be avoided or attempts should be made to correct the anemia. Anemia caused by ribavirin can be life-threatening for persons with certain types of heart or blood vessel disease. Ribavirin causes birth defects and pregnancy should be avoided during treatment. Patients and their healthcare providers should carefully review the product manufacturer information prior to treatment.

Treatment for symptoms or side effects due to antiviral treatment

You should report what you are feeling to your doctor. Some side effects may be reduced by giving interferon at night or lowering the dosage of the drug. In addition, flu-like symptoms can be reduced by taking acetaminophen before treatment.

The Food and Drug Administration has approved the use of the combination anti-viral therapy for the treatment of hepatitis C in children 3 to 17 years old.

Recommendations for Assessment Prior to Treatment and Monitoring During and After Therapy: AASLD Practice Guidelines 2009

“

1. Treatment decisions should be individualized based on the severity of liver disease, the potential for serious side effects, the likelihood of treatment response, the presence of comorbid conditions, and the patient’s readiness for treatment (Class IIa, Level C). 2. For patients in whom liver histology is available, treatment is indicated in those with bridging fibrosis or compensated cirrhosis provided they do not have contraindications to therapy (Class I, Level B). 3. The optimal therapy for chronic HCV infection is the combination of peginterferon alfa and ribavirin (Class I, Level A). 4. HCV RNA should be tested by a highly sensitive quantitative assay at the initiation of or shortly before treatment and at week 12 of therapy, (Class I, Level A). Genotypes 1 and 4 HCV infection 1. Treatment with peginterferon plus ribavirin should be planned for 48 weeks; the dose for peginterferon alfa-2a is 180 µg subcutaneously per week together with ribavirin using doses of 1,000 mg for those <75 kg in weight and 1,200 mg for those >75 kg; the dose for peginterferon alfa-2b is 1.5 µg/kg subcutaneously per week together with ribavirin using doses of 800 mg for those weighing <65 kg; 1,000 mg for those weighing >65 kg to 85 kg, 1,200 mg for >85 kg to 105 kg, and 1,400 mg for >105 kg (Class I, Level A). 2. Treatment may be discontinued in patients who do not achieve an early virological response (EVR; >2 log reduction in HCV RNA at week 12 of treatment) (Class I, Level A). 3. Patients who do not achieve a complete EVR (undetectable HCV RNA at week 12 of treatment) should be re-tested at week 24, and if HCV RNA remains positive, treatment should be discontinued (Class I, Level A). 4. For patients with genotype 1 infection who have delayed virus clearance (HCV RNA test becomes negative between weeks 12 and 24), consideration should be given to extending therapy to 72 weeks (Class IIa, Level B). 5. Patients with genotype 1 infection whose treatment continues through 48 to 72 weeks and whose measurement of HCV RNA with a highly sensitive assay is negative at the end of treatment should be retested for HCV RNA 24 weeks later to evaluate for a sustained virological response (SVR; HCV RNA negative 24 weeks after cessation of treatment) (Class I, Level A) Genotype 2 or Genotype 3 HCV Infection 1. Treatment with peginterferon plus ribavirin should be administered for 24 weeks, using a ribavirin dose of 800 mg (Class I, Level A). 2. Patients whose treatment continues through 24 weeks and whose measurement of HCV RNA with a highly sensitive assay is negative should be retested for HCV RNA 24 weeks later to evaluate for an SVR (Class I, Level A). 3. Patients with HCV-related cirrhosis who achieve an SVR, regardless of the genotype, should continue to be monitored at 6 to 12 month intervals for the development of HCC (Class IBold textIa, Level C).

”

Recommendations for Retreatment of Persons Who Failed to Respond to Previous Treatment : AASLD Practice Guidelines 2009

“

1. Retreatment with peginterferon plus ribavirin in patients who did not achieve an SVR after a prior full course of peginterferon plus ribavirin is not recommended, even if a different type of peginterferon is administered (for relapsers, Class III, Level C; for non-responders, Class III, Level B). 2. Retreatment with peginterferon plus ribavirin can be considered for non-responders or relapsers who have previously been treated with non-pegylated interferon with or without ribavirin, or with peginterferon monotherapy, particularly if they have bridging fibrosis or cirrhosis (Class IIa, Level B). 3. Maintenance therapy is not recommended for patients with bridging fibrosis or cirrhosis who have failed a prior course of peginterferon and ribavirin (Class III, Level B)

”

.

Recommendations for Treatment of Persons with Normal Serum Aminotransferase Values: AASLD Practice Guidelines 2009

“

1. Regardless of the serum alanine aminotransferase level, the decision to initiate therapy with pegylated interferon and ribavirin should be individualized based on the severity of liver disease by liver biopsy, the potential for serious side effects, the likelihood of response, and the presence of comorbid conditions (Class I, Level B). 2. The treatment regimen for HCV-infected persons with normal aminotransferase levels should be the same as that used for persons with elevated serum aminotransferase levels (Class I, Level B).

”

Recommendations for Treatment of Persons with Acute Hepatitis C: AASLD Practice Guidelines 2009

“

1. Patients with acute HCV infection should be considered for interferon-based anti-viral therapy (Class I, Level B). 2. Treatment can be delayed for 8 to 12 weeks after acute onset of hepatitis to allow for spontaneous resolution (Class IIa, Level B). 3. Although excellent results were achieved using standard interferon monotherapy, it is appropriate to consider the use of peginterferon because of its greater ease of administration (Class I, Level B). 4. Until more information becomes available, no definitive recommendation can be made about the optimal duration needed for treatment of acute hepatitis C; however, it is reasonable to treat for at least 12 weeks, and 24 weeks may be considered (Class IIa, Level B). 5. No recommendation can be made for or against the addition of ribavirin and the decision will therefore need to be considered on a case-by-case basis (Class IIa, Level C)

”

References