Management of Decompensated HCV Cirrhotic Patients
Condition: Decompensated Cirrhosis
MeSH terms: Liver Cirrhosis; Fibrosis
Study type: Interventional

Summary: 
      -The limited treatment varieties of decompensated cirrhosis due to hepatitis C virus (HCV)
      remain a challenge. In patients with reduced hepatic reserve, DAAs may be associated with
      complications as worsening decompensation. The impact of DAAs therapy on mortality in
      decompensated cirrhosis was not investigated.
    

Detailed description: 
      An observational case-control study which was conducted from June 2015 till the first of
      January 2018 in the Hepatology clinic - Zagazig University hospital-Egypt which is a tertiary
      referral center.

      Out of 422 patients presented with decompensated cirrhosis due to HCV, 342 patients were
      excluded due to Hepatocellular carcinoma (n=61), cirrhotic cardiomyopathy (n=21), renal
      impairment (n=34), ischemic heart disease (n=37), active gastrointestinal bleeding (n=42),
      avoided treatment with DAAs and preferred conservative therapy (n=147); finally 80 patients
      with decompensated cirrhosis who were willing to be treated and showed frequent hepatic
      encephalopathy (HE) or difficult to treat ascites were selected to receive DAAs and included
      if they had chronic HCV proved by the positivity of HCV RNA and elevated transaminases. Their
      CTP score was >9, MELD score was <29 Patients were excluded if they had compensated cirrhosis
      or HCV without cirrhosis; exposure to previous antiviral therapy; hepatocellular carcinoma;
      other causes of liver diseases or mixed causes as excessive alcohol consumption, autoimmune
      liver disease; previous liver transplantation; patients with risk factors of myocardial
      dysfunction as abnormal T wave in electrocardiogram, ejection fraction (EF) less than 50%,
      left ventricular ejection fraction (LVEF) less than 50%.

      The control group included 80 patients; they sought medical care at the Hepatology outpatient
      clinic-Zagazig University hospital. They had decompensated liver disease and preferred to be
      managed conservatively; they desired to avoid treatment by DAAs by themselves (n=43) or by
      their relatives (n=37) as they were concerned about the potential risk of liver cancer after
      direct antiviral agents. They were age, sex, CTP and MELD scores matched with the same
      inclusion and exclusion criteria and had been chosen from the patients who refused the
      treatment with DAAs (n=147) after their consent to participate in the study, while the
      remaining patients refused to be enrolled (n=67).

      B-Baseline laboratory investigation

        -  Investigations preliminary to antiviral therapy as liver function tests, Prothrombin
           time, Prothrombin concentration (%), kidney function tests, complete Blood Count,
           fasting blood sugar, HBA1c if diabetes was present and serum AFP. For each patient, CTP
           and MELD scores were calculated.

        -  Quantitative assessment of HCV load in the serum by real-time Quantitative PCR (COBAS
           Ampliprep/Taqman HCV monitor version 2.0, with a detection limit of 15 IU/ml; Roche
           Diagnostic Systems, just before the study in both groups and after the first month, at
           the end of treatment and 3 months post-treatment to detect SVR 12th in DAAs treated
           group

        -  Genotyping for HCV using INNO-LiPA II, based on genotype-specific oligonucleotides from
           the 5' UTR that are immobilized on a nitrocellulose strip. The probe reactivity patterns
           were interpreted according to the manufacturer instructions.

      C- Abdominal Ultrasonography (USG) The patients were evaluated for criteria of decompensated
      cirrhosis including shrunken cirrhotic liver and ascites, patients with HCC were excluded.
      Criteria of portal hypertension as portal vein diameter > 13mm or cavernous transformation,
      splenic bipolar diameter >13 cm, splenic vein diameter >8 mm or the presence of splenic
      collaterals. After treatment termination; USG was done every 6 months for a period of 20
      months for early detection of HCC or worsening of hepatic decompensation.

      D- Treatment exposure and outcome

        -  Medications The study patients will be given Sofosbuvir 400mg, ribavirin 400mg, and
           daclatasvir 60 mg for 3 months and will be evaluated for the development of sustained
           virological response (SVR), the occurrence of complications after DAAs and the effects
           of SVR on the frequency of hepatic encephalopathy, improvement in ascites control or
           difficult to treat ascites defined as ascites that rapidly recurs after paracentesis or
           cannot be completely mobilized despite maximal medications (sodium restriction of less
           than 2 g/day with maximal dose of furosemide (160 mg) or spironolactone (400 mg) or
           inability to reach maximum diuretic dose due to emergence of side effects, and after
           confirming compliance with sodium restrictions if the 24-hour urine sodium level is <78
           mEq, also the impact of therapy on Survival.

        -  Monitoring

        -  All the patients will have regular biweekly visits in the first 6 months then every 2
           months for 20 months. Every visit a full history taking, laboratory evaluation which
           included complete blood count (CBC), serum creatinine, total and direct bilirubin, serum
           albumin, serum transaminases, coagulation profile and AFP.

      The patients who did not complete the follow-up will be excluded from the study.
    

Intervention name(s): Sofosbuvir 400mg (Sovaldi) + Daclatasvir 60 mg (Daklinza) + Ribavirin 200 mg (Rebetol); vitamin K (Phytomenadione) 10 mg+ furosemide and spironolactone (Lasilactone) 50 mg + milk thistle (Silymarin) 140 mg + Albumin infusion
Intervention type(s): Drug; Drug
Intervention description(s): sofosbuvir 400mg+ribavirin 400mg+daclatasvir 60 mg were adminstered for 3 months; symptomatic therapy for liver support, control of ascites and bleeding tendency.
Other intervention name(s): Direct Acting Antivirals (DAAs); liver support therapy
Intervention MeSH terms: Vitamin K; Vitamin K 1; Ribavirin; Sofosbuvir; Furosemide; Spironolactone; Silymarin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: patients with decompensated cirrhosis with frequent hepatic encephalopathy (HE) or difficult to treat ascites were included if they had chronic active HCV
Masking: None (Open Label)
Primary purpose: Treatment