Cirrhosis, Liver
Conditions
Keywords
Growth hormone, cirrhosis
Brief summary
Liver cirrhosis (LC) is a leading cause of morbidity and mortality worldwide. Life- threatening complications of liver cirrhosis are ascites, gastrointestinal bleeding, variceal bleed, hepatic encephalopathy and hepatocellular carcinoma (HCC) which are associated with poor prognosis.The leading causes of liver cirrhosis include excess alcohol consumption, viral hepatitis and non-alcoholic fatty liver disease. Malnutrition is common in end-stage liver disease (cirrhosis) and is often associated with a poor prognosis. It occurs in all forms of cirrhosis with different etiology and prevalence ranges from 65 to 100% depending upon the methods used for nutritional assessment and the severity of liver disease. Nutritional state influences survival in patients with decompensated cirrhosis. Protein malnutrition manifested by reduced skeletal muscle mass and hypoalbuminemia, exist in patients with cirrhosis despite apparent adequate food consumption and these patients have a higher rate of complications and, overall, an increased mortality rate. Also, Malnutrition has significant implications for liver transplantation; patients with poor nutritional status before transplantation have increased complications and higher mortality rates postoperatively. Screening all patients with chronic liver disease for nutritional abnormalities can identify those at risk of developing preventable complications. Malnutrition is commonly associated with protein catabolism and the protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3. GH therapy in cirrhosis has been shown to improve nitrogen economy and to improve the GH resistance in a small pilot study by Donaghy et al. Also, GH therapy of short duration has shown to increase IGF1 levels, IGFBP-3 levels in patients of cirrhosis. GH therapy has also shown to improve liver regeneration and protein synthesis after hepatectomy in patients of HCC with cirrhosis. However there is scarcity of data on clinical impact of long term administration of GH therapy in patients of cirrhosis. Hence, we undertook the present study to study the effect of growth hormone on nitrogen economy, malnutrition and liver regeneration in patients with cirrhosis.
Interventions
DRUGStandard Medical Therapy
Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required
DRUGGrowth Hormone
GH therapy is initiated at a low dose of 1U/day and titrated slowly upward to a maximum dose of 3U/day (depending on IGF-1 levels) subcutaneously for 1 year.
Sponsors
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Decompensated Cirrhosis of liver irrespective of etiology
Exclusion criteria
* Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF) * Splenic diameter of more than 18 cm * Concomitant HCC or other active malignancy * Upper gastrointestinal bleeding in the previous 7 days * Portal vein thrombosis * Severe renal dysfunction as defined by creatnine \> 1.5mg/dl * Severe cardiac dysfunction * Uncontrolled diabetes (Hb A 1c ≥ 9) or diabetic retinopathy * Acute infection or disseminate intravascular coagulation * Active alcohol abuse in last 3 months * Known hypersensitivity to GH * HIV co-infection * Pregnancy * Refusal to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Nutritional status based on CT L3 SMI score. | One year | Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Mid arm muscle circumference(MAMC) | One year | — |
| Improvement in hand grip strength | One year | Hand grip strength will be measured with the hydraulic hand dyanamometer in Kg/force. |
| Clinical improvement in liver function | One Year | Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed |
| Improvement in BMI | One Year | — |
| Improvement in Quality of life | One Year | Quality of life will be assessed using SF-36V2 Health Survey questionnaire |
| Improvement in liver regeneration | One Year | By measuring hepatic parenchymal cell specific marker (CD 133) and cell proliferation marker (Ki-67) by immunohistochemistry. |
| Biochemical improvement in liver function | One year | Improvment in MELD score |
Countries
India
Outcome results
None listed