MadSci Network: Anatomy

Re: How long does it take a human liver to completely regenerate itself?

Date: Thu Feb 5 12:17:05 2004
Posted By: June M. Wingert , RM (NRM) ,Associate Scientist
Area of science: Anatomy
ID: 1075335690.An

The following Abstract from the authors "Yamanaka N. Okamoto E. Kawamura 
E. Kato T. Oriyama T. Fujimoto J. Furukawa K. Tanaka T. Tomoda F. Tanaka 
W."  will shed some light on the kinetics of the regeneration of the Liver.

The information was taken from the following website

Dynamics of normal and injured human liver regeneration after hepatectomy 
as assessed on the basis of computed tomography and liver function. 
Hepatology. 18(1):79-85, 1993 Jul. 
Abstract We compared liver volume and function kinetics after partial 
hepatectomy according to extent of resection and severity of coexisting 
liver disease in 57 adults with uneventful postoperative courses. Liver 
volume and massiveness of resection, or resection rate, were estimated on 
computed tomography. Patients were categorized into three groups on the 
basis of reaction rate: small (< 30%), medium (30%-50%) and large (> 50%). 
The regenerative patterns of normal livers in the medium and large groups 
consisted of three phases: a rapid increase during the first month, some 
decrease in the second month and a final, slower increase. This contrasted 
with the pattern of injured livers with chronic hepatitis or cirrhosis, 
which generally showed a phase of less rapid, gradual increase. The 
regeneration rate (volume gain, cm3/day) during the first month was found 
to be proportional to resection rate in the presence or absence of liver 
disease. Normal livers regenerated at least twice as rapidly as injured 
livers in patients with comparable resection rates. Normal livers reached 
plateau levels within 1 to 2 mo regardless of the massiveness of 
resection, whereas regeneration took 3 to 5 mo in injured livers. Liver 
function (albumin, bilirubin) recovered concomitantly with liver volume in 
the medium group, whereas in the large group they generally returned to 
their initial values behind volume restoration, particularly in cirrhotic 
patients. In conclusion, human liver regeneration is strongly influenced 
by the massiveness of the resection and presence of coexisting liver 
disease. However, we found that some cirrhotic livers can regenerate, 
albeit more slowly and less completely, as long as the extent of 
hepatectomy remains within safe functional limits.

You might also have an interest in reading the article below taken from 
the website located at:

The liver has a remarkable capacity to regenerate after injury and to 
adjust its size to match its host. Within a week after partial 
hepatectomy, which, in typical experimental settings entails surgical 
removal of two-thirds of the liver, hepatic mass is back essentially to 
what it was prior to surgery. Some additional interesting observations 
include: 	In the few cases where baboon livers have been 
transplanted into people, they quickly grow to the size of a human liver.
	When the liver from a large dog is transplanted into a small dog, 
it loses mass until it reaches the size appropriate for a small dog.
	Hepatocytes or fragments of liver transplanted in extrahepatic 
locations remain quiescent but begin to proliferate after partial 
hepatectomy of the host. These types of observations have prompted 
considerable research into the mechanisms responsible for hepatic 
regeneration, because understanding the processes involved will likely 
assist in treatment of a variety of serious liver diseases and may have 
important implications for certain types of gene therapy. A majority of 
this research has been conducted using rats and utilized the model of 
partial hepatectomy, but a substantial body of confirmatory evidence has 
accumulated from human subjects. The Dynamics of Liver RegenerationPartial 
hepatectomy leads to proliferation of all populations of cells within the 
liver, including hepatocytes, biliary epithelial cells and endothelial 
cells. DNA synthesis is initiated in these cells within 10 to 12 hours 
after surgery and essentially ceases in about 3 days. Cellular 
proliferation begins in the periportal region (i.e. around the portal 
triads) and proceeds toward the centers of lobules. Proliferating 
hepatocytes initially form clumps, and clumps are soon transformed into 
classical plates. Similarly, proliferating endothelial cells develop into 
the type of fenestrated cells typical of those seen in sinusoids. It 
appears that hepatocytes have a practically unlimited capacity for 
proliferation, with full regeneration observed after as many as 12 
sequential partial hepatectomies. Clearly the hepatocyte is not a 
terminally differentiated cell. Changes in gene expression associated with 
regeneration are observed within minutes of hepatic resection. An array of 
transcription factors (NF-kB, STAT3, fos and jun) are rapidly induced and 
probably participate in orchestrating expression of a group of hepatic 
mitogens. Proliferating hepatocytes appear to at least partially revert to 
a fetal phenotype and express markers such as alpha-fetoprotein. Despite 
what appears to be a massive commitment to proliferation, the regenerating 
hepatocytes continue to conduct their normal metabolic duties for the host 
such as support of glucose metabolism. Stimuli of Hepatic 
RegenerationHepatic regeneration is triggered by the appearance of 
circulating mitogenic factors. This conclusion was originally supported by 
experiments demonstrating that quiescent fragments of liver that had been 
transplanted to extrahepatic sites would begin to proliferate soon after 
partial hepatectomy, and also that hepatectomy in one of a pair of 
parabiotic rats led to hepatic proliferation in the other of the pair. As 
might be expected, liver regeneration seems to be supported by a group of 
mitogens and growth factors acting in concert on several cell types. Some 
of the major and well-studied players that act together in this process 
include: 	Hepatocyte growth factor (scatter factor) levels rise to 
high levels soon after partial hepatectomy. This is the only factor tested 
that acts by itself as a potent mitogen for isolated hepatocytes cultured 
in vitro. This factor is also of critical importance in development of the 
liver, as target deletions of its gene lead to fetal death due to hepatic 
insufficiency. 	TNF-alpha, which stimulates proliferation of 
hepatic endothelial cells. 	Interleukin-6, which acts as a biliary 
epithelial mitogen. 	Epidermal growth factor. 	Norepinephrine 
potentiates the mitogenic activity of EGF and HGF. 	Insulin is 
required for regeneration but appears to play a permissive rather than 
mitogenic role. The processes and signals involved in shutting down the 
regenerative response are less well studied than those that stimulate it. 
TGF-beta1, which is known to inhibit proliferative responses in 
hepatocytes, is one cytokine involved in this process, but undoubtedly 
several others participate. 

Thank for taking the time to send in a question to the MAD SCI NETWORK
June Wingert
Associate Scientist
Biotechnology Firm in Texas

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