Chittoor Mohammed Habibullah

Human Fetal Liver-Derived Stem Cell Transplantation as Supportive Modality in the Management of End-Stage Decompensated Liver Cirrhosis:

Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a few people. With a tremendous upsurge in the mortality rate of patients with liver disorders worldwide, there is a need to search for an alternative therapeutic tool that can combat the above limitations and serve as a supportive therapy in the management of liver diseases. Cell therapy using human fetal liver-derived stem cells can provide great potential to conservatively manage end-stage liver diseases. Therefore, the present investigation aimed to study and prove the safety and efficacy of human fetal liver-derived stem cell transplantation in patients with end-stage liver cirrhosis. Twenty-five patients with liver cirrhosis of different etiologies were infused with human fetal liver-derived stem cells (EpCAM+ve) labeled with Tc-HMPAO through hepatic artery. Our high throughput analysis using flow cytometry, RT-PCR, and cellular characterization exemplifies fetal liver cells with their high proliferation rate could be the best source for rejuvenating the diseased liver. Further, no episodes related to hepatic encephalopathy recurred in any of the subjects following hepatic stem cell transplantation. There was marked clinical improvement observed in terms of all clinical and biochemical parameters. Further, there was decrease in mean MELD score (p < 0.01) observed in 6 months follow-up in all patients. Therapy using human fetal liver stem/progenitor cells offers a potentially supportive modality to organ transplantation in the management of liver diseases.

Geographical difference in antimicrobial resistance pattern of Helicobacter pylori clinical isolates from Indian patients: Multicentric study

Aim:  To assess the pattern of antimicrobial resistance of Helicobacter pylori isolates from peptic ulcer disease patients of Chandigarh, Delhi, Lucknow, Hyderabad and Chennai in India, and to recommend an updated anti‐H. pylori treatment regimen to be used in these areas.

Safety and Efficacy of Autologous Bone Marrow Stem Cell Transplantation Through Hepatic Artery for the Treatment of Chronic Liver Failure: A Preliminary Study

This study was performed to determine the safety and tolerability of injecting autologous bone marrow stem cells (BMC) (CD34+) into four patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony stimulating factor (G-CSF) mobilized blood and autologous bone marrow contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated the CD34+ stem cell population from the bone marrow. The potential of the BMC to differentiate into hepatocytes and other cell lineages has already been reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into hepatocytes. Recently Sakaida demonstrated reduction in fibrosis in chemically induced liver cirrhosis following BMC transplantation. From a therapeutic point of view, chronic liver cirrhosis is one of the targets for BMC transplantation. In this condition, there is excessive deposition of extracellular matrix and hepatocyte necrosis. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte-like elements, four patients with liver insufficiency were given G-CSF to mobilize stem cells. CD34+ cells (0.1 x 10(8)) were injected into the hepatic artery. No complications or specific side effects related to the procedure were observed; four patients showed improvements in serum albumin, bilirubin and ALT after one month from the cell infusion.

Treatment of Crigler-Najjar Syndrome Type 1 by Hepatic Progenitor Cell Transplantation: A Simple Procedure for Management of Hyperbilirubinemia

Crigler-Najjar Syndrome (CNS) is characterized by mild, chronic unconjugated hyperbilirubinemia resulting from an autosomal-recessive inherited deficiency of hepatic uridine/diphosphoglucuronate-glucuronosyl transferase 1Al since birth. Herein we have reported a confirmed case of CNS type 1 in a 2-year-old girl with an unconjugated hyperbilirubinemia (>30 mg/dL) treated by hepatic progenitor cell infusion through the hepatic artery. No procedure-related complications were encountered. No kernicterus was observed. The total bilirubin started falling at 10 days after cell infusion. Two months after cell infusion the bilirubin fell from 29.0 to 16 mg/dL, with the conjugated bilirubin increasing approximately fivefold, the unconjugated bilirubin decreasing nearly twofold, and the SGPT also decreasing from 210 U/L to 64 U/L. This study demonstrated the efficacy of hepatic progenitor cells to manage hyperbilirubinemia in these patients. As the procedure is simple and the patient has tolerated the cell therapy, infusion can be repeated as required to manage hyperbilirubinemia, which often causes lethal kernicterus. This study was developed to assess the safety, feasibility, and efficacy of hepatic progenitor cell transplantation in a child with CNS type 1.

Management of Hyperbilirubinemia in Biliary Atresia by Hepatic Progenitor Cell Transplantation Through Hepatic Artery: A Case Report

Cholangiodestruction of bile ducts leads to biliary atresia, a rare disease characterized by intrahepatic and extrahepatic biliary inflammation. If the intrahepatic biliary tree is unaffected, surgical reconstruction by the Kasai procedure of hepatoportoenterostomy of the extra hepatic biliary tract is possible. Untreated, this condition leads to cirrhosis and death within the first year of the life. If the atresia is complete, liver transplantation is the only option. As a result of the shortage of donor livers, hepatocytes have been infused over the past two decades, providing proof of the concept that cell therapy can be effective for the treatment of liver diseases. In the present study, we report a confirmed case of a girl of 1 year of age with increased bilirubin of 28.5 mg/dL and pediatric end-stage liver disease score 20. Biochemical liver function tests showed cholestasis (elevated cholesterol and gamma-GTs) and increased ALT, total bilirubin, conjugated bilirubin, and ALP. The patient was treated with hepatic progenitor cell infusion through the hepatic artery. The total bilirubin and conjugated bilirubin started decreasing during the first month after cell infusion. The level of total bilirubin maintained a threefold decrease after months of cell infusion. The conjugated bilirubin was 16.35 mg/dL before cell infusion, decreasing to eightfold after cell infusion. After 2 months of cell infusion, hepatobiliary scintigraphy showed increased liver cell function. This case demonstrated the efficacy and functionality of hepatic progenitor cells for the management of biliary atresia. Further, as there was a decrease in serum bilirubin, it showed that there was some percentage of the engraftment of the infused cells. As the procedure is simple and the patient has tolerated the infusion therapy, it might be repeated to manage biliary atresia.

Polymerase chain reaction based analysis of the cytotoxin associated gene pathogenicity island of Helicobacter pylori from saliva: an approach for rapid molecular genotyping in relation to disease status.

Background and Aims: The genetic composition of the intricate cytotoxin associated gene pathogenicity island (cag PAI) of Helicobacter pylori is known to significantly influence the outcome of the disease. Hence, analysis of complete cag PAI of H. pylori isolated from saliva would be of immense importance in standardizing saliva as a reliable non‐invasive diagnostic specimen and also to evaluate the type of H. pylori infection. The aim of the present study was to analyze the genes of cag PAI of H. pylori for their presence and correlating them with the disease status of the patients.

A simple multiplex PCR assay for diagnosing virulent Helicobacter pylori infection in human gastric biopsy specimens from subjects with gastric carcinoma and other gastro-duodenal diseases

Aim:  To evaluate and develop a multiplex polymerase chain reaction (PCR) assay for diagnosing and specific identification of virulent Helicobacter pylori strains and their main virulence genes cagA, cagE, cagT, vacA and hrgA.

Comparison of biochemical and cytotoxic functions of hepatocytes from goat, pig and human fetuses.

Background and Aim:  To overcome the problem of shortage of donor organs, xenotransplantation of cells offers an alternative to orthotopic transplantation. Of the higher animals, the pig is considered as a suitable donor because of the similarity in size and function of pig organs to human organs. However, successful transplantation of pig organs/cells for human therapy is limited by hyperacute rejection, improper functioning of xenografts and the risk of transmission of endogenous retroviruses to the recipient. Thus, there is a pressing need to explore an alternate mammalian source to bridge the gap between the donor and the recipient waiting for transplantation. This has warranted us to explore the application of goat hepatocytes as a treatment modality in acute liver failure.

In Vivo Identification, Survival, and Functional Efficacy of Transplanted Hepatocytes in Acute Liver Failure Mice Model by FISH Using Y-Chromosome Probe

Hepatocyte transplantation has excited much interest in lending temporary metabolic support to a failing liver following acute liver injury. The exact site from which they act and the clinical, biochemical, and histological changes in the recipient body following hepatocyte transplantation is yet to be worked out. The present study is an attempt to delineate location and function of transplanted hepatocytes and also the overall survival of these cells with a fluorescent in situ hybridization (FISH) technique using a Y-chromosome-specific probe in a carbon tetrachloride (CCl4)-induced mice model of fulminant hepatic failure. Fifty-five syngenic adult Swiss female mice of approximately the same age and body weight were divided into three groups. Group-1 (n = 15), which received mineral oil, served as a negative control. Group-II (n = 15) received CCl4 (3 mL/kg) 40% vol/vol in mineral oil, by gavage served as positive control for hepatic failure. Group-III (n = 25) received intrasplenic transplantation of syngenic single cell suspension of hepatocytes in Hanks medium, after 30 h of CCl4 administration. Male Swiss adult mice (n = 15) served as donors of hepatocytes. The overall survival of animals in groups I to III was 100, 0, and 70%, respectively, by 2 wk of the study period. Transplanted hepatocytes were identified by Periodic Acid Schiff (PAS) staining and confirmed with a FISH technique using the Y-chromosome probe. The majority of exogenously transplanted hepatocytes were found in the liver and spleen sections even after 1 wk of hepatocyte transplantation. Transplanted cells were mostly found to be translocated into the sinusoids of the liver. Transplanted hepatocytes were found to be beneficial as a temporary liver support in a failing liver, significantly improving the survival of the animals. In the present study, the FISH technique was used to unequivocally distinguish the transplanted cells from the host, and thus describes a model for studying the distribution and survival of the transplanted cells.

Prevalence, risk factors and genotype distribution of HCV and HBV infection in the tribal population: a community based study in south India

Prevalence, risk factors and genotype distribution of HCV and HBV infection in the tribal population: a community based study in south India