Nontransplant options for the treatment of metabolic liver disease: Saving livers while saving lives

Balistreri, William F.

doi:10.1002/hep.1840190335

Cited by 20 publications

(3 citation statements)

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“…Several lines of investigation now fully support this concept, as recently reviewed in a publication of a symposium on intrahepatic cholestasis (2). His eloquent writing on “saving livers while saving lives” highlights his enthusiasm for non‐transplant options for the treatment of metabolic liver diseases (3), and represents editorial comments that will not age.…”

Section: Introductionmentioning

confidence: 99%

The Next Challenge in Pediatric Cholestasis

Bezerra

2006

J. pediatr. gastroenterol. nutr.

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Cholestasis is a common presenting symptom of liver disease in infants. Chief among diseases presenting as neonatal cholestasis is biliary atresia, the most common cause of chronic liver disease in children, but little is known about the pathogenesis of this disease. In search for the molecular basis of biliary atresia, we began two areas of investigation. In the first, we interrogated the hepatic transcriptome of children with biliary atresia and found an interferon-gamma (IFNgamma)-rich proinflammatory footprint at the time of diagnosis. To directly explore if IFNgamma plays an important role in biliary injury and obstruction, we used a mouse model of experimental biliary atresia and found that inactivation of the murine Ifngamma gene decreases the tropism of lymphocytes to neonatal bile ducts and prevents the inflammatory obstruction of the duct lumen. Further analysis of the extrahepatic biliary tract also outlined a broader network of proinflammatory genes at the onset and during progression to duct obstruction, with the time-specific activation of IFNgamma-, apoptosis-, and complement-driven networks. In the second approach, we searched for molecular profiles that differentiate clinical forms of biliary atresia by analyzing the hepatic transcriptome of age-matched subjects at the time of diagnosis. We found a preliminary profile that differentiates the embryonic from the perinatal forms of biliary atresia. The profile contained the differential activation of genes involved in epigenetic mechanisms of disease. Collectively, these studies provide new insight into pathogenesis of biliary atresia and identify potential therapeutic targets to foster long-term outcome with the native liver.

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Section: Introductionmentioning

confidence: 99%

The Next Challenge in Pediatric Cholestasis

Bezerra

2006

J. pediatr. gastroenterol. nutr.

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“…There are few reports published concerning arterial occlusive vasculopathy after LTx. In general, it is an observation made in cases with chronic rejection (14–16). In our group there was no child suffering from clinical chronic rejection, but arterial transplant vasculopathy cannot be ruled out as we did not perform routine graft biopsies in stable patients.…”

Section: Discussionmentioning

confidence: 81%

Development of liver size and perfusion after reduced‐size liver transplantation in children

Hoyer

Rodeck

Scherbring

et al. 2001

Pediatric Transplantation

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The technique of segmental liver transplantation (s-LTx) provides a method to overcome the shortage of suitable livers for small recipients. Patient survival rates are parallel to those obtained with whole liver transplantation (w-LTx). For long-term rehabilitation, adaptive liver growth and adequate perfusion is crucial; however, morphometric and hemodynamic parameters in growing children with s-LTx are not available. Seventeen children who received a s-LTx and 25 with a w-LTx who had follow-up evaluation 1 and 2 yr after LTx were studied. Mean age at time of transplantation was 4.3 +/- 3.5 yr for s-LTx and 10.3 +/- 6.0 yr for w-LTx, mean height 98 +/- 21 cm and 122 +/- 30 cm respectively. At follow-up evaluation mean values for liver enzymes, bilirubin and prothrombin time were in the normal ranges for both groups. Liver dimensions were measured by gray scale ultrasound, and hemodynamic parameters by Doppler sonography in the portal vein and hepatic artery using an Acuson 128 machine. Maximal (Vmax), minimal (Vmin) and time-average velocity (TAV) were measured and the resistive index (RI) calculated. We found that 1 and 2 yr after LTx liver dimensions were at a mean in the upper normal range of healthy controls. Spleen size was above the normal range and did not show any tendency towards regression. Mean Vmax in the hepatic artery in s-LTx and w-LTx was 48 cm/sec vs. 28 cm/sec after 1 yr and 30 cm/sec vs. 35 cm/sec after 2 yr, the RI 0.66 vs. 0.55 and 0.59 vs. 0.73, respectively (p for all parameters > 0.05). Maximal portal vein flow was 25 cm/sec in s-LTx vs. 29 cm/sec in w-LTx. Blood flow calculated by vessel diameter and TAV showed no statistical difference between both groups. In conclusion, liver size after s-LTx and w-LTx was increased to the upper normal range, and portal vein blood flow velocities were within the normal range. Vmax in the hepatic artery was reduced in s-LTx; however, the reduction was to the same extent as in w-LTx. In the view of long-term functional adaptation, s-LTx is not inferior to w-LTx.

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“…Enigmatic disorders presenting as acute liver failure, chronic hepatitis, or hepatocellular carcinoma yielded to biochemical analysis and molecular dissection and were proven to be caused by inborn errors of lipid, amino acid, or carbohydrate metabolism. The recognition of the metabolic basis for liver disease allowed for targeted nontransplant strategies for the management of affected patients . In addition, early practitioners of Pediatric Hepatology in Taiwan were largely responsible for the initial steps towards reducing the global burden of hepatitis B .…”

Section: Other Significant Advancesmentioning

confidence: 99%

Growth and development of a new subspecialty: Pediatric hepatology

Balistreri

2013

Hepatology

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Several major forces converged to catalyze the formal emergence of a body of knowledge and an organized focus on disorders of the liver in early life. Attendant to the development of a focused clinical subspecialty the pace of patient-and laboratory-based research in the field quickened in parallel to decipher the consequences of genetic or metabolic aberrations on immature liver structure and function. The key research observations that catalyzed the emergence and subsequent rapid growth of Pediatric Hepatology include: (1) an understanding of the dynamic events occurring during hepatobiliary development and the importance of these physiologic variables that occur during liver maturation; (2) the recognition of the unique nature of inherited and acquired liver diseases that affect infants and children-such as biliary atresia and Reye's syndrome; and (3) redefinition of the once obscure inherited intrahepatic cholestatic diseases of the liver, which, in turn, provided insight into normal and abnormal hepatobiliary physiology. The clinical advances were highlighted by the development of specific approaches to the diagnosis and management of liver disease in infants and children, including both liver transplantation and nontransplant treatment options. These seminal events led to the expansion of the workforce, creating a critical mass consisting of individuals with focused, specialized skills and techniques. In-depth expertise allowed more accurate diagnosis and highly effective treatment strategies for advanced hepatobiliary disease in children. The demand for pediatric clinicians with experience in advanced hepatology allowed sub-sub-specialization to flourish. Continued maturation of the field led to definition of hepatology-focused curricular elements and educational content for Pediatric Gastroenterology training programs, and subsequently the development of program requirements for those who wished to acquire additional training in Pediatric Hepatology. A significant rite of passage was marked by the election of pediatric hepatologists to leadership positions in the American Association for the Study of Liver Diseases (AASLD). Further validation of the field occurred with approval of the petition for establishing a Certificate of Added Qualification in Transplant Hepatology by the American Board of Pediatrics. Here I relate my perspective on the history of the advances in our field and the contributions of many of the clinicians and scientists whose efforts led to the development of focused clinical, research, and training programs that improved the care of children with diseases of the liver. (HEPATOLOGY 2013;58:458-476) The ChallengeSince there was not a single linear pathway it appeared at first to be a daunting task to reconstruct the history and sequence of events leading to the emergence and maturation of a field of subspecialization. Therefore, it was a bit overwhelming to be asked by the editors of HEPATOLOGY to "look back on my career" and not only "tell us about your life story" but also "illus...

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Nontransplant options for the treatment of metabolic liver disease: Saving livers while saving lives

Cited by 20 publications

References 50 publications

The Next Challenge in Pediatric Cholestasis

The Next Challenge in Pediatric Cholestasis

Development of liver size and perfusion after reduced‐size liver transplantation in children

Growth and development of a new subspecialty: Pediatric hepatology

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