1) Lamlvudine reduces post-transplant recurrence of Hepatitis B virus infection & can delay the need for Liver Transplantation in some patients with Chronic Hepatitis B

At the 50^th annual meeting of the American Association for the Study of Liver Diseases held in November 1999 at Dallas, Texas, new data was presented that indicated that the oral antiviral medicine, Lamlvudine, had a very important role to play in liver transplant patients with chronic hepatitis B.

Lamlvudine, used in a once-daily dosage for compensated chronic hepatitis B, reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation. It also delayed or potentially removed the need for liver transplantation in some patients, and alleviated the clinical signs of liver failure-end points. This could all be viewed as positive signals for improved survival.

Approximately   350 million people are long-term, chronic carriers of the hepatitis B virus (1) and upto 40% of those who become infected die as a consequence of cirrhosis and liver cancer (2) A liver transplant operation is often the only option left to patients with life-threatening hepatitis B induced liver damage, but because the virus is present in tissues outside the liver and in the blood at the time of the transplant procedure, patients undergoing transplant surgery run a high risk of HBV re-infection occurring in the grafted organ. Such recurrent HBV infections after transplantation generally have a poor prognosis and are often fatal. In this light, many liver transplant centres will not offer liver transplantation to end stage hepatitis B patients unless adequate suppression of HBV infection can be achieved.

A North American, multicenter study evaluated the efficacy and safety of Lamlvudine in suppressing HBV replication prior to and following liver transplantation. A total of 77 patients were enrolled in this open-label, uncontrolled study and received Lamlvudine 100 mg daily prior to anticipate surgery. The study then divided into two arms, one looking at the incidence of re-infection post-transplant, and the other evaluating the disease outcomes for those patients who did not progress to transplantation.

In 34 of 47 patients who received a liver transplant and who were evaluated at one year following surgery, 71% (24/34) were hepatitis B surface antigen negative, indicating no re-infection. This figure is higher than historical expectations (3) for post-transplant re-infection. 7 other patients who had received transplant were not evaluated at one year. Mortality in the post-transplant period occurred in 6 patients, and it was usually related to post-surgical complications. Over all , most patients were clinically stable one year following liver transplantation and have now been enrolled in a five-year study of continued treatment.

In addition, 27 of 77 enrolled patients did not undergo anticipated liver transplant. Study data suggest disease stabilisation in these patients as indicated by improvements in serum markers of liver function (ALT, bilirubin, and albumin). However, six of these 27 patients did not survive primarily due to complications of their advanced liver disease. In the 21 surviving patients, Lamlvudine therapy for a median duration of approximately two years was generally well-tolerated in this relatively ill population.

Dr. Robert Perrillo, Director of Gastroenterology and Hepatology, Ochsner clinic, New Orleans, and the lead investigator of the study explained: “We set out to evaluate the extent to which Lamlvudine prevented re-infection with HBV following transplant surgery. We have seen that Lamlvudine therapy reduces the proportion of patients with HBV re-infection post-transplant and that most patients were clinically stable one year following liver transplantation.”

In three placebo-controlled clinical trials, the most common adverse events observed in patients treated with Lamlvudine (vs. placebo) were ear, nose and throat infections (21%); malaise and fatigue (28%); and headache (21%).

Safety and efficacy of lamuvidine has not been established in patients with decompensate liver disease or organ transplants. The optimum duration of treatment with lamuvidine, the loss of HBsAg, the durability of HBeAg seroconversions occurring during treatment, and the relationship of initial treatment response to outcomes such as hepatocellular carcinoma and decompensate cirrhosis are not known. The reappearance of assay-detectable HBA DNA during Lamlvudine treatment was observed in approximately one third of patients after initial response. Post-treatment exacerbations of hepatitis B have occurred. Most events appear to be self-limiting. Fatalities have been reported in some cases. The casual relationship to discontinuation of Lamlvudine treatment is unknown. Lactic acidosis are severe hepatomegaly with steatosis, including fatal cases, have been reported rarely with the use of nucleoside analogues alone or in combination, including Lamlvudine and other antiretroviral.

Human immunodeficiency virus (HIV) counselling and testing should be offered to all patients before beginning Lamlvudine and periodically during treatment, because Lamlvudine is used in a lower dose in hepatitis B as compared to that used to treat HIV infection. Rapid emergence of HIV resistance is likely because of sub therapeutic dose and inappropriate monotherapy.

1. The World Health Report. WHO 1998.
2. Mast EE, Alter MJ. Epidemiology of viral hepatitis: an overview. Sem Virol 1993; 4:273-283.
3. Samuel et al.N Engl J Med 1993:329:1842-1847.

ii) Liver Transplant possible for Alcoholic Cirrhosis, according to study

According to a report that appeared in Gut(1999:45;421-426), G-P.Pageaux and his colleagues from Saint Eloi Hospital in Montpellier, France, have said that  liver transplantation is justified for alcoholic cirrhosis. They felt that the good results obtained in this area would help them to educate the general population about alcoholic liver disease.

Their study included 53 patients who received liver transplantation for alcoholic cirrhosis and 48 patients who received transplants for non-alcoholic liver disease between 1989 and 1994. One- and five-year survival rates were similar between the two groups: 75% and 62%, respectively, for the patients with alcoholic cirrhosis and 83% and 61% respectively, for patients with non-alcoholic liver disease.

The authors also studied a number of variables. Recovery of employment (30%) and non-alcoholic (60%) patients who survived more than 3 months after transplantation. 6 alcoholic patients and 7 non-alcoholic patients required re-transplantation.

“The major argument against wide spread use of liver transplantation for patients with alcoholic cirrhosis has been the fear of high rate of recidivism leading to loss of the graft,” the author said. However, the 32% overall rate of recidivism the observed in their patients did not affect survival and compliance with immunosuppressive therapy.

ii) LIVER TRANSPLANT FOR HEPATITIS C

Hepatitis C virus is the most common chronic blood borne infection in the United States as an estimated 3.9 million Americans have antibodies to HCV and 2.7 million people Americans are chronically infected with a virus. Hepatitis C commonly leads to the need for a liver transplant.

The estimate of the seroprevalence of HCV is the result of a study by Mariam J. Alter, PhD, and colleagues at the centres for disease control and prevention that was published on August 19, 1999 testing for antibody to HCV on serum samples from 21, 241 people who participated in the 3^rd National Health and Nutrition Examination Survey, which was conducted from 1988 to 1994.

Among the sub group of participants who were 17 to 59 years old, the strongest factors independently associated with infection were illegal drug use and high-risk sexual behaviour. Other factors associated with infection were poverty, fewer than 13 years of education, and having been divorced or separated. The study excluded people who were jailed or homeless- two groups that have high rates of HCV infection and this means that the actual figures could be much higher.

To prevent new infections, the authors suggested that “Public Health Programmes should focus on preventing the initiation of high-risk drug-related and sexual behaviour and on providing risk-reduction counselling and services to those engaged in high-risk activities”.