Neil Canavan

November 15, 2011

November 15, 2011 (San Francisco, California) — A new treatment regimen with the low-molecular-weight heparin enoxaparin reduced the incidence of portal vein thrombosis (PVT), leading to fewer events of clinical decompensation and enhanced survival in patients with advanced cirrhosis, according to data presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

"PVT occurs in up to 25% of patients with advanced cirrhosis," said Erica Villa, MD, from the University of Modena and Reggio Emilia in Italy. There are several clinical implications of PVT, including worsening of portal vein hypertension, onset of refractory ascites, increased occurrence of encephalopathy, and increased complications related to organ transplantation.

To address the issue of PVT, Dr. Villa and colleagues treated patients with advanced cirrhosis with enoxaparin 4000 IU/day subcutaneously for 1 year, followed by a second year of observation. Results from the treated group were compared with an untreated group of similar patients over the same time period.

"This study covers new ground," said Dr. Villa, "because anticoagulation therapy has never been prospectively tested for PVT prevention."

A total of 70 cirrhotic patients (Child-Pugh score of B7 to C10) were randomized in a 1:1 ratio to treatment with enoxaparin or placebo. To check for portal vein axis, patients were monitored for PVT every 3 months with ultrasound and every 6 months with computed tomography. PVT was considered relevant when it was complete or when it involved more than 50% of portal vein diameter and was symptomatic.

The study population was 50% male and a mix of cirrhotic patients with hepatitis B virus, hepatitis C virus, or alcoholic liver disease plus HCV plus nonalcoholic steatohepatitis, with a median MELD score of 13. Median age was 57 years. Patients had to be free of ascites at the time of enrollment.

At 24 months, there was a significant improvement in outcomes with enoxaparin. After 1 year of treatment, there were 6 PVT events in the placebo group (n = 36) and no events in the enoxaparin group. At the 2-year time point, there were 4 more PVT events in the placebo group and 3 events in the enoxaparin group.

"The probability of PVT was significantly higher in the untreated cases," said Dr. Villa.

"Most interesting was the occurrence of decompensation," she said. There was a significant difference in the enoxaparin group both after 1 year of treatment and at the 2-year follow-up.

There were 22 events at 1 year and 48 more at 2 years in the placebo group, compared with 4 events at 1 year and 11 events at 2 years in the enoxaparin group (P = .014). "This translates into a probability of developing decompensation of 25% at 1 year with no treatment, compared with 10% for enoxaparin, and at 2 years, 48% compared with 24% — again favoring enoxaparin," said Dr. Villa.

Not surprisingly, this reduction in events led to a significant improvement in overall survival in the enoxaparin group (P = .02), although causes of death were similar between groups. The most frequent causes of death were sepsis and liver failure. There were 4 cases of hepatocellular carcinoma reported — 3 in the enoxaparin group and 1 in the placebo group.

There were no bleeding events related to active treatment. One patient in the enoxaparin group discontinued treatment because of asymptomatic thrombocytopenia.

Results Impressive — So Far

"Patients with liver disease have low platelet counts, so they're at a high risk of bleeding already because of esophageal varicies," said transplant hepatologist Pratima Sharma, MD, from the University of Michigan in Ann Arbor. "It's that risk of bleeding that I think outweighs [the benefits of] this approach, but this is something new, and they didn't seem to see any higher risk of bleeding in their enoxaparin-treated group."

Still, for a number of reasons, Dr. Sharma doesn't think these data should guide a change in practice — not yet. "The definitions of decompensation were not very clear, and most of the patients had a Child score of 7 (30 of 34), which means someone without ascites and hepatic encephalopathy." Validation of the approach should include a broader range of patients with cirrhosis.

Dr. Villa and Dr. Sharma have disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting: Abstract 120. Presented November 7, 2011.

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