Drug To Treat Progressive Liver Disease Shows Promise

Pentoxifyline, a drug used to improve blood flow, is showing promise in the treatment of non‐alcoholic steatohepatitis (NASH), a liver disease causing increasing concern in the US. NASH is a common, often “silent” liver disease. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.

NASH affects 2 to 5 percent of Americans. An additional 10 to 20 percent of Americans have fat in their liver, but no inflammation or liver damage, a condition called “fatty liver.” Although having fat in the liver is not normal, by itself it probably causes little harm or permanent damage. If fat is suspected based on blood test results or scans of the liver, this problem is called nonalcoholic fatty liver disease (NAFLD). If a liver biopsy is performed in this case, it will show that some people have NASH while others have simple fatty liver.

Both NASH and NAFLD are becoming more common, possibly because of the greater number of Americans with obesity. In the past 10 years, the rate of obesity has doubled in adults and tripled in children. Obesity also contributes to diabetes and high blood cholesterol, which can further complicate the health of someone with NASH. Diabetes and high blood cholesterol are also becoming more common among Americans.

Two  studies  presented  at  the  75th  Annual  Scientific  Meeting  of  the  American  College  of  Gastroenterology  investigated  the  effetiveness  of  potential  treatments  for  NASH,  one  assessing  pentoxifylline, used to improve blood flow. It works by decreasing the thickness (viscosity) of blood.  The other study was an analysis of  pioglitazone,  an  insulin  sensitizer,  compared  to  vitamin  E.   

Claudia  O.  Zein,  M.D.  and  colleagues  at  the  Cleveland  Veterans  Affairs  Medical  Center  and  the  Cleveland  Clinic  in  Cleveland,  OH  conducted  a  double‐blinded,  randomized,  placebo‐controlled  trial  of  pentoxifylline  in  patients  with  NASH. 

“The  higher  frequency  of  biochemical  and  histological  improvement  observed  in  our  study  among  patients  who  received  pentoxifyllie  compared  to  placebo,  suggest  both  a  reason  for  hope  and  a  need  for  further  studies,”  added  Dr.  Zein.  

Advertisement

She  advises  that  physicians  should  suspect  and  investigate  for  fatty  liver  disease  among  patients  who  are  at  high  risk,  including  those  who  are  overweight,  diabetic,  or  have  other  elements  of  the  metabolic  syndrome.   “General  recommendations  in  the  management  of  patients  with  fatty  liver  disease  include  weight  reduction  for  obese  patients,  and  optimized  management  of  the  components  of  the  metabolic  syndrome,  if  present.   However,  there  is  still  a  need  for  effective  medical  therapeutic  agents  for  NASH,  and  that  is  why  the  results  of  this  study  are  so  encouraging,”  Dr.  Zein  concluded.    

Although  insulin  sensitizers  have  been  the  main  focus  for  developing  new  treatments  for  NASH,  the  study  by  Dr.  Zein  and  another  study indicates  that  pathways  other  than  insulin  resistance  could  be  used  for  developing  effective  treatments  for  NASH.   

Advertisement

In their study titled “Changes  in  Adipose  Tissue  Insulin  Resistance  Correlate  with  Changes  in  Liver  Histology  in  NASH  Patients  who  Participated  in  thePIVENS  Trial,”  Lauren  Bell,  Ph.D.  and  colleagues  from  Indiana  University  School  of  Medicine   investigated  whether  changes  in  insulin  resistance  are  responsible  for  the  improvement  in  liver  histology  seen  with  vitamin  E.     

Non‐diabetic  adult  patients  with  NASH  were  randomized  to  receive  pioglitazone  (a  drug  used  in  Type  2  diabetes),  vitamin  E,  or  placebo  and  followed  after  96  weeks  of  treatment.

“Although  Adipo‐IR  was  not  different  from  placebo  in  either  treatment  group  after  96  weeks,  there  were  trends  for  improvement  with  pioglitazone  and  worsening  of  Adipo‐IR  with  vitamin  E,  suggesting  that  the  positive  effect  of  vitamin  E  on  liver  histology  is  independent  of  changes  in  adipose  tissue  insulin  resistnce,”  explained  Dr.  Bell.  

The  mechanism  by  which  vitamin  E  improves  liver  histology  remains  unknown  but  it  is  thought  to  be  due  to  its  intrahepatic  antoxidant  effects.   Dr.  Bell’s  finding  that  increases  in  Adipo‐IR  correlated  with  worsening  fibrosis,  if  confirmed,  could  be  an  important  non‐invasive  test  for  monitoring  liver  fibrosis  in  patients  with  NASH.     

Source-Medindia