Hepatitis: McCashland T

Gish RG, McCashland T. · Department of Transplantation and Medicine, California Pacific Medical Center, San Francisco, CA, USA. · Liver Transpl. · Pubmed #17051551 links to  free full text

Abstract: KEY CONCEPTS: 1. The use of low-dose immunosuppressive therapy along with pre- and posttransplantation nucleos(t)ide therapy and posttransplantation hepatitis B immunoglobulin (HBIG) has yielded marked improvements in survival. 2. Lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), tenofovir (Viread), emtricitabine (Emtriva), and the combination drugs tenofovir + emtricitabine (Truvada) and abacavir + lamivudine (Epzicom) are effective nucleos(t)ide antiviral agents that, in some cases, may help reverse liver disease sufficiently to avoid transplant. 3. In posttransplantation patients, virus suppression with some combination of HBIG and the nucleos(t)ide agents may prevent graft loss and death or the need for a second transplant. 4. In both the pre- and posttransplantation setting, the goal of hepatitis B virus management is complete virus suppression. 5. The use of low-dose intramuscular HBIG is evolving, with studies showing that dosing and cost can be reduced by 50-300% with a customized approach. 6. Elimination of HBIG from the treatment paradigm is currently under evaluation and may be possible with the use of newer medications that have no or low resistance rates. 7. Although there is growing evidence that some types of combination therapy may decrease the chance that drug resistance will develop and increase the likelihood of long-term success in preventing graft loss and death, additional research will be required to determine which combinations will work well in the long term, and which will not.

Crippin JS, McCashland T, Terrault N, Sheiner P, Charlton MR. · Baylor University Medical Center, Dallas, TX, USA. · Liver Transpl. · Pubmed #11965579 links to  free full text

Abstract: Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNA-positive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 x 10(6) U/d; (2) group B, interferon alfa-2b, 3 x 10(6) U three times weekly; or (3) group C, interferon alfa-2b, 1 x 10(6) U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis.

McCashland T, Watt K, Lyden E, Adams L, Charlton M, Smith AD, McGuire BM, Biggins SW, Neff G, Burton JR, Vargas H, Donovan J, Trotter J, Faust T. · Department of Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA. · Liver Transpl. · Pubmed #17763405 links to  free full text

Abstract: It is widely perceived that outcomes are relatively poor following retransplantation (reTX) for recurrent of hepatitis C virus (HCV) infection. Transplant centers debate the utility of offering another liver to these patients. A U.S. study group was formed to retrospectively compare survival after reTX in patients with recurrent HCV (histologically proven) and those transplanted for other indications greater than 90 days after first transplantation, from 1996 to 2004. Patients were divided into 3 groups; group 1: HCV reTX (n = 43), group 2: non-HCV reTX (n = 73), and group 3: recurrent HCV but no reTX (n = 156). They were predominantly male, Caucasian, with mean age of 47.2 yr. The commonest indications for non-HCV reTX were chronic rejection (36%), hepatic artery thrombosis (31%) and recurrent primary sclerosing cholangitis (17%). Duration of hospitalization, number of intensive care unit (ICU) days, and time interval from listing to transplantation or reTX were similar between reTX groups. The 1-yr and 3-yr survival rates after reTX were also similar for HCV reTX and non-HCV reTX groups (1 yr, 69% vs. 73%; 3 yr, 49% vs. 55%). Model for End-Stage Liver Disease (MELD) scores were not predictive of survival from reTX. However, with a MELD score of >30 in the non HCV group, survival was <50%. In the recurrent HCV not undergoing reTX group, 30% were reevaluated for reTX but only 15% were listed for reTX and the 3-yr survival was 47%. The most common reasons for not listing for reTX were recurrent HCV within 6 months (22%), fibrosing cholestatic hepatitis (19%), and renal dysfunction (9%). In conclusion, patients retransplanted for recurrent HCV had similar 1-yr and 3-yr survival when compared to patients undergoing reTX for other indications. MELD scores were not predictive of post-reTX survival. Survival was <50% in the non-HCV reTx group with MELD score of >30. Many patients with recurrent HCV are not considered for reTX and die from recurrent disease.

McCashland T. · Department of Internal Medicine, Gastroenterology, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA. · Liver Transpl. · Pubmed #17051554 links to  free full text

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