SUMMARY: As people survive longer after liver transplants, the development of metabolic syndrome is a growing concern -- an epidemic waiting to happen -- according to a review article published in the December 2009 issue of Liver Transplantation. Studies indicate that diabetes, hypertension, and other manifestations of the syndrome are more common in liver transplant recipient than in similar non-transplant patients. These conditions increase the risk of cardiovascular disease, and indicate the need for better management including lifestyle modifications and lipid-lowering drugs.

By Liz Highleyman

Over years or decades, chronic hepatitis B or C infection can progress to advanced liver damage that necessitates a transplant. As post-transplant survival has improved, metabolic syndrome and its individual components -- including diabetes mellitus, hypertension, dyslipidemia (abnormal blood fat levels), and obesity -- are increasingly recognized as a contributor to cardiovascular complications and late morbidity and mortality, wrote Mangesh Pagadala and colleagues from the Digestive Disease Institute of the Cleveland Clinic Foundation.

The prevalence of post-transplant metabolic syndrome and its components has been found to be higher in transplant recipients (43%-58% after 12 to 18 months) compared with an otherwise comparable population who do not receive transplants (about 25%). The development of nonalcoholic fatty liver disease (NAFLD) after liver transplantation (for reasons other than non-NAFLD cirrhosis) is also increasingly recognized.

Most patients with liver disease severe enough to require a transplant have some degree of insulin resistance, and this typically improves after transplantation. Persistent or newly emerging insulin resistance post-transplantation, however, is a cause for concern.

Several potential pre-transplant risk factors for post-transplant metabolic syndrome have been identified, including older age, male sex, history of smoking, higher pre-transplant body mass index (of the liver recipient or donor), and pre-transplant diabetes.

Patients who receive transplants due to hepatitis C, alcoholic cirrhosis, or cryptogenic (unknown cause) cirrhosis are also at higher risk. Another risk factor is immunosuppression, caused by drugs used to prevent organ rejection (also suggesting potential concern for people with HIV).

Patients with post-transplant metabolic syndrome have an increased risk of cardiovascular events, organ rejection, and all types of infection, the researchers noted. According to one study, the risk of cardiovascular events was about 30% among people who developed post-transplant metabolic syndrome, compared with 8% among people who did not. However, the overall impact of metabolic syndrome on long-term survival and mortality remains to be determined.

Strategies to reduce the development of metabolic syndrome -- both before and after transplantation -- should include lifestyle modifications involving improved diet, increased physical activity, and weight loss, they concluded. Additional measures that may be beneficial include use of lipid-lowering medications, optimal blood glucose control, and use of tacrolimus instead of cyclosporine for immune suppression.

Department of Gastroenterology & Hepatology and Department of Hepatobiliary Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH.

1/15/10

Reference
M Pagadala, S Dasarathy, B Eghtesad, and AJ McCullough. Posttransplant metabolic syndrome: an epidemic waiting to happen. Liver Transplantation 15(12): 1662-1670 (Abstract). December 2009.

Researchers keep hepatitis C at bay after liver transplant

Washington, Jan 1 In most patients who undergo a liver transplant because of liver failure or liver cancer, the new liver becomes infected with the hepatitis C virus (HCV) almost immediately. But now researchers have developed an approach that transiently keeps HCV levels down in most HCV-infected patients receiving a new liver.
Hideki Ohdan, Kazuaki Chayama and colleagues at Hiroshima University in Japan, took immune cells known as lymphocytes from the donor livers before they were transplanted into the HCV-infected patients, activated them in0-vitro, and then injected them into the patients three days after they had received their liver transplants.

Importantly, these infused cells were able to

keep HCV at bay even though the patients were taking immuno-suppressive drugs to prevent their immune systems from rejecting the new livers.

Despite showing clear clinical effects, the authors are planning further studies in which they will modify the protocol in an attempt to find a way to keep HCV levels down for longer and in all patients, says a Hiroshima release.

These findings were published in the Journal of Clinical Investigation.

http://www.thaindian.com/newsportal/health1/researchers-keep-hepatitis-c-at-bay-after-liver-transplant_100297493.html

Liver Lines 2010

Written by David Bernstein, MD

2010 promises to be a better year than 2009. With the onset of a new year and a new decade, we are filled with renewed hope and promise that things will get better. This New Year will bring lots of change. We will see new leaders, new policies and hopefully new peace and prosperity. With all this hope, my thoughts turn to liver transplantation and all of our neighbors out there who could benefit from this medical miracle.

Liver transplantation has rapidly advanced over the past two decades to become standard therapy for patients with end-stage liver disease. Children and adults with congenital and acquired disorders are candidates for transplantation. The most common indications for liver transplantation in the United States include viral hepatitis B and C, non-alcoholic fatty liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease, in-born errors of metabolism, autoimmune disease, fulminant hepatic failure and liver tumors.

Liver transplantation involves removing the diseased liver from a patient with advanced liver disease and replacing it with a new, healthy liver from a donor. The surgery is performed in very specialized centers by surgeons dedicated to this operation. Unfortunately, the number of people waiting for a liver transplant far outnumbers the supply of donor livers. This leads to long waiting times and many patients do not survive their liver disease while on the list awaiting liver transplantation. We are getting better, however.

Liver transplantation is not indicated for all people with cirrhosis. It is indicated only for those people whose livers are not working properly. These end-stage complications include bleeding from distended veins in the esophagus and stomach, the filling of the abdomen with fluid called ascites, the onset of severe confusion termed encephalopathy or the development of liver cancer. Many people come to my office after being diagnosed with liver disease of any cause and are scared because they believe they will need a liver transplant in the near future. The good news is that only a very small percentage of people with liver disease will advance to end-stage disease and need a transplant.

Overall survival rates for liver transplantation in the United States are excellent. The in-hospital recovery period after surgery is highly variable with many transplant recipients being discharged within one week of surgery. After transplantation, the patients are placed on immunosuppressive therapy which is generally life-long. These medications are usually well tolerated but occasionally patients can have side-effects related to these medicines.

A shortage of donor livers is one of the major problems facing patients with liver disease in the United States. As a result, many children and adults die waiting for a liver transplant. Due to this shortage, the federal government and the non-profit United Network for Organ Sharing (UNOS) have been working together to establish strict guidelines for organ allotment. In an effort to increase donor numbers, transplant centers have begun to perform adult living-related liver transplantation. In this procedure, a relative or friend donates a portion of his/her liver to the person with end stage liver disease. Hopefully, through these tremendous acts of giving, more lives will be saved.

I would like to wish all the readers a happy, healthy and prosperous New Year. Please do not forget all those in need and in the spirit of giving, please remember to consider organ donation to aid the thousands of children and adults in our area in need of liver transplantation.

Dr. Bernstein is the director of Hepatology for the North Shore-Long Island Jewish Health System. You may write to Dr. Bernstein, c/o Anton Community Newspapers, 132 E. Second Street, Mineola, NY 11501 or email dbernste@nshs.edu .

(Disclaimer: The views and opinions represented are those of the author and meant for informative purposes only. For your specific questions, consult your physician.)

http://www.antonnews.com/roslynnews/opinion/5070-liver-lines-december-31-2009.html

Evolution of Hepatitis C Virus in Liver Allografts
www.newsrx.com

Research conducted at University of Pittsburgh has provided new information about the hepatitis C virus

According to recent research published in the journal Liver Transplantation, "Hepatitis C virus (HCV) RNA+ liver allograft recipients invariably reinfect the liver allograft within hours after transplantation, and the majority (>70%) develop chronic hepatitis."

The rate at which these patients experience progression to cirrhosis and the overall percentage are significantly increased in comparison with HCV infection in the nontransplant setting.

Core needle biopsy evaluation is used to establish the diagnosis of recurrent HCV, which can be difficult to distinguish from acute cellular rejection and other causes of allograft dysfunction. In the vast majority of cases, however, distinguishing recurrent HCV from other posttransplant syndromes is reliably achieved by a careful examination of hematoxylin and eosinstained sections and correlation with clinical and serological data.

Recurrent HCV often coexists with other causes of liver allograft dysfunction, and the determination of the most important cause of injury and whether other causes of injury are present is important. Included are residual changes of preservation/reperfusion injury, biliary sludging/structuring, acute cellular and chronic rejection, and autoimmune hepatitis.

The complex interplay between immunosuppression management, viral replication, and the recipient immune system results in distinct patterns of recurrent chronic HCV in the liver allograft: (1) conventional or usual acute and chronic HCV, which resembles that seen in the general population with HCV; (2) fibrosing cholestatic hepatitis; and (3) plasma cell-rich HCV, which might represent a variant of, or overlap with, autoimmune hepatitis and rejection.

The variable but usually hastened histopathological progression toward cirrhosis in HCV+ allografts is similar to that seen in the nontransplant setting, but in allografts, the overall severity of lymphocytic inflammation is less, and ductular reactions, stellate cell activation, and subsinusoidal fibrosis are accentuated. Hepatic stressors and causes of an impaired ability of hepatocytes to replicate include persistently high levels of viral replication, HCV-specific CD4+ T responses, advanced donor age, high levels or rapid withdrawal of immunosuppression, and coexistent liver damage from preservation/reperfusion injury, biliary structuring, or coexistent cytomegalovirus or herpes 6 viral infection.

Immunological effector mechanisms involved in the rejection and control of HCV replication/HCV elimination show significant overlap with very high levels of HCV RNA rarely show[ing] significant clinically significant acute or chronic rejection, whereas their occurrence is frequently associated with very low levels or clearance of HCV RNA

The researchers concluded: "Studying the evolution from recurrent HCV to acute rejection in patients treated with interferon and/or weaned from immunosuppression might provide valuable insights into the relationship between these 2 processes as well as liver allograft: acceptance."

Demetris and colleagues published their study in Liver Transplantation (Evolution of Hepatitis C Virus in Liver Allografts. Liver Transplantation, 2009;15(11 Suppl.):S35-S41).

For additional information, contact A.J. Demetris, University of Pittsburgh, Dept. of Pathology, Medical Center, Division Transplantation, Room E741, 3459 5th Avenue, Pittsburgh, PA 15213, USA.