Effects of Harvoni in Patients With Decompensated Cirrhosis Due to Hepatitis C Genotype 1 Infection
Condition: Hepatitis C, Chronic; Cirrhosis, Decompensated
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 3

Summary: 
      There are now several licensed drug treatments for patients with HCV infection. These
      medications have been shown to be very effective in getting rid of the virus in patients with
      HCV infection including those with early stages of cirrhosis without complications known as
      compensated cirrhosis, with a greater than 90% cure rate. At present, there are very little
      data to show that treating patients with HCV infection and decompensated cirrhosis will give
      the same effects. However, patients with decompensated cirrhosis as a result of hepatitis B
      infection who received treatment to control their virus show improvement of their overall
      liver condition, and the liver complications of many of these patients disappeared. Also,
      patients with cirrhosis due to excess alcohol and who stopped drinking also showed
      improvement in liver function and their complications of cirrhosis coming under control.
      Therefore, treatment of patients with HCV infection and decompensated cirrhosis is expected
      to show the same positive effects, because the underlying cause of cirrhosis is coming under
      control. Harvoni is a combination of two direct-acting antivirals (ledipasvir and sofosbuvir)
      that prevents the hepatitis C virus from copying and multiplying themselves, allowing the
      body to clear the virus from their systems and be cured of HCV infection. This study is being
      conducted to find out if treatment with Harvoni will lead to clearance of HCV infection in
      patients with decompensated cirrhosis giving rise to improvement in liver function, together
      with improvement of quality of life and survival.
    

Detailed description: 
      Hepatitis C virus (HCV) is one of the most common causes of liver cirrhosis worldwide. The
      progression of liver cirrhosis can lead to a myriad of complications including ascites,
      variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, and hepatocellular
      carcinoma. The development of these complications or decompensation can lead to a dismal
      survival of 50% at 6 months, especially if the underlying cause of the liver cirrhosis is not
      treated. The cost of caring for these patients with decompensated cirrhosis is extremely
      high. Despite this, every effort is being made to maintain these patients in reasonable
      health until liver transplant becomes available for them. Yet these patients continue to have
      poor quality of life because of the various symptoms related to decompensated cirrhosis, and
      spend much time visiting health care facilities for both outpatient and inpatient care.

      The recent availability of potent and effective anti-viral therapy has revolutionized the
      management of patients with hepatitis C infection. With a >90% cure rate, many patients with
      compensated cirrhosis, once treated, will not progress further to develop decompensation.
      With the passage of time, the liver cirrhosis may even regress to a non-cirrhotic state.
      Published data on treatment of decompensated cirrhosis with hepatitis C infection is still
      scanty. However, patients with decompensated cirrhosis due to hepatitis B infection who
      received effective anti-viral therapy not only improved their overall clinical status, many
      of these patients reverted from a decompensated to a compensated state, associated with
      improved survival. Likewise, patients with alcoholic cirrhosis who abstain from alcohol will
      also have improvement in liver function and reduction in complications of cirrhosis.
      Therefore, treatment of decompensated cirrhotic patients with hepatitis C is expected to show
      the same beneficial effects, because the underlying cause of cirrhosis is coming under
      control.

      The primary objective of this study is to assess the effects of anti-viral therapy on the
      clinical status, quality of life and survival of patients with decompensated cirrhosis due to
      chronic hepatitis C genotype 1 infection.

      After completion of all initial investigations, patients will be started on Harvoni 90 mg
      ledipasvir/400 mg sofosbuvir (one tablet) daily. The course of treatment will be 24 weeks.
      Patients will be reviewed at monthly intervals as per standard of care. At each clinic visit,
      patients with have blood tests including complete blood count, renal function, electrolytes,
      liver enzyme and liver function tests, HCV RNA will be done at week 4, week 12, week 24
      during treatment, and then again at week 12 post completion of treatment. Annual ultrasounds
      and surveillance gastroscopies will be organized as per standard of care.

      Patient will be followed for 1 year post completion of treatment, and have repeat quality of
      life questionnaires at end of treatment, and thereafter at 6 and 12 months. Patients will
      also be monitored for the development of further complications of cirrhosis (if any),
      hospital admissions, reasons for hospital admissions, lengths of hospital stays, survival,
      and liver transplantation.
    

Intervention name(s): Ledipasvir/Sofosbuvir
Intervention type(s): Drug
Intervention description(s): Each tablet of Harvoni contains 90 mg ledipasvir and 400 mg sofosbuvir.
Other intervention name(s): Harvoni
Intervention MeSH terms: Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment