Growth Hormone Therapy in Liver Cirrhosis

Study Overview
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Brief Summary
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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.

Official Title
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Growth Hormone Therapy and Its Effect on Nitrogen Metabolism and Malnutrition in Liver Cirrhosis

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Drug: Standard Medical Therapy
* Drug: Growth Hormone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Medical Therapy<br>Standard medical therapy: diuretics, lactulose, rifaximin, diuretics, albumin infusion, nutritional support (as required) | Drug: Standard Medical Therapy<br>* Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required<br>|
| Active Comparator: Growth hormone<br>Growth Hormone: GH therapy is initiated at a low dose of 1U/day and titrated slowly upward to a maximum dose of 3U/day (based on IGF-1 levels) subcutaneously for 1 year. | Drug: Standard Medical Therapy<br>* Standard Medical Therapy will include nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics as required<br>Drug: Growth Hormone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Nutritional status based on CT L3 SMI score. | Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in BMI |  | One Year | 
| Improvement in Mid arm muscle circumference(MAMC) |  | One year | 
| Improvement in hand grip strength | Hand grip strength will be measured with the hydraulic hand dyanamometer in Kg/force. | One year | 
| Clinical improvement in liver function | Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed | One Year | 
| Biochemical improvement in liver function | Improvment in MELD score | One year | 
| Improvement in Quality of life | Quality of life will be assessed using SF-36V2 Health Survey questionnaire | One Year | 
| Improvement in liver regeneration | By measuring hepatic parenchymal cell specific marker (CD 133) and cell proliferation marker (Ki-67) by immunohistochemistry. | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth hormone, cirrhosis