Every year millions of patients die due to liver dysfunction all over the world. The liver failure can be broadly classified into acute and chronic liver failures. Though the cause and pathogenesis are vast to be covered herein, a brief note our involvement in both the types is given below.
Acute liver failure: NCRMs research work:
The acute liver failure which occurs during pregnancy, due to drug toxicity or acute phase of a chronic liver failure in which a temporary Liver function support would save the life, has been our main focus. If the liver function can be supported until either the pregnancy period is over (upon delivery) or toxicity inducing drug is withdrawn and ill effects wean, then total recovery is considered almost certain, provided native liver repair mechanisms play their role. At present Molecular Absorbent Recirculatory System (MARS) has been the only answer for a transient support. Though there have been several reports on MARS in the literature from developed countries, in India, handling of such acute liver failure has been reported only in a very few centers.
We have been collaborating with Dr C.M.Habibullah et al to find a solution for rescuing the acute liver failure patients using cell therapeutics. Dr C.M. Habibullah et al of the present Centre for Liver Research & Diagnostics, Owaisi Hospital, Hyderabad have earlier tried using Fetal hepatocytes from aborted fetuses to rescue acute liver failure cases by transplanting them suspended in saline into the intra peritoneal space of the patients with successes (As reported in the publication: Transplantation; 1994 Oct 27; 58(8): 951-2., Human fetal hepatocyte transplantation in patients with fulminant hepatic failure.,Habibullah CM, Syed IH, Qamar A, Taher-Uz Z).
The major obstacles they found with continuing the same treatment further were:
(i) Non-availability of adequate amount of fetal liver substance for transplantation
(ii) Methods to expand the fetal liver cells in vitro without animal proteins
(Though Matrigel is usable for expansion, since it is an animal protien, the expanded hepatocytes with Matrigel cannot be transplanted in situ)
(iii) In vivo inadequate survival span of the transplanted fetal cells until the recovery from the acute liver failure.
We have been successful in (1) encapsulating the hepatocytes and (2) injecting them into intraperitoneal cavity of CCL4 treated liver injury model animals and then (3) have proven that the encapsulated cells thus injected successfully recover the animals against their controls as published in Hepatitis Monthly (1)
(1) Praveen N, Khan AA, Baskar S, Habeeb MA, Babu R, Abraham S, Yoshioka H, Mori Y, Mohammed HC. Intraperitoneal Transplantation of Hepatocytes Embedded in Thermoreversible Gelation Polymer in Acute Liver Failure Rat Model. Hepatitis Monthly 2008; 8(4): 275-280
(2) Capoor AK, Khan AA, Habibullah CM. In vitro Assessment of Microencapsulation in providing immunoprotection against antibody-mediated cell Lysis. Acta Medica et Biologica 1999; 47 (3) : 97-102
(3) Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, Okita K. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40(6):1304-11.
Chronic liver failure due to Liver Cirrhosis : NCRMs clinical trials:
Liver Cirrhosis being caused mainly by Viral infections (Hepatitis B & hepatitis C) and Alcoholism, the end stage liver failure following liver cirrhosis can be treated only by liver transplantation, in which either a cadaver donors liver or a living related (within the family) donors liver has to be transplanted to the patient. Liver Transplantation, apart from being expensive, it is also marred by the necessity of a donor liver and the lack of necessary expertise in several hospitals to an extent. To rescue such patients, stem cell therapy (from the patients own bone marrow) was started by Prof. Isao Sakaida of Yamaguchi University, Japan and upon a collaboration with his team, NCRM has brought this clinical solution to India, probably the first time from a pioneer. (Click for details)