Effects of Harvoni in Patients With Decompensated Cirrhosis Due to Hepatitis C Genotype 1 Infection
Effects of Harvoni in Patients With Decompensated Cirrhosis Due to Hepatitis C Genotype 1 Infection
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.
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.
Inclusion Criteria:

 Treatment-naïve and treatment-experienced patients with CHC genotype 1 infection and
 decompensated cirrhosis as defined by one of the following:

 -  history of variceal bleeding

 -  presence or history of ascites

 -  history of grade III-IV hepatic encephalopathy

 -  Coagulopathy with an INR>1.7

 -  Jaundice with a serum bilirubin of >85µmol/L

 Cirrhosis is defined as any one of the following:

 -  A liver biopsy performed prior to the study showing cirrhosis (F4)

 -  Fibroscan performed within 12 calendar months of the start of this study with a result
 of > 12.5 kPa

 -  A Fibrotest ® score of >0.75

 Exclusion Criteria:

 -  Patients older than 75 years

 -  Presence of hepatoma at entry

 -  Patients awaiting living-related liver transplantation

 -  MELD score of >30

 -  Significant co-morbid condition(s) with a life expectancy of <6 months

 -  HIV co-infection

 -  HBV co-infection