Liver transplantation (OLTx) has become a common procedure at many centers in Europe and North America. The 1 and 5 year survival of patients receiving liver transplants at most centers is 75-85% and 60-65% respectively. As such, many physicians, in addition to those at transplant centers, will be called upon to see and care for recipients surviving liver transplants. The gastrointestinal tract is a common site of post-transplantation problems. These problems involve all components of the gastrointestinal tract. Many have characteristic, if not unique, presentations and clinical courses. They are reviewed for the physician in clinical practice who does not practice at a transplant center.

Biliary Tract Diseases↗

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Unusual indications for liver transplantation.

This paper is an attempt to present some of the unusual indications for OLTx that are occasionally seen at transplant centers. It is not an all-encompassing treatise but rather an attempt to present the more usual of the unusual indications for OLTx. As such, it is a framework to which readers could add any we do not mention as and when they are encountered in their own practice.

Cystic Fibrosis↗

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gamma-Glutamyl transpeptidase as a response predictor when using alpha-interferon to treat hepatitis C.

BACKGROUND/AIMS: This study was performed to identify response predictors for Interferon therapy given to patients with chronic hepatitis C. MATERIALS AND METHODS: The biochemical measures of liver injury that characterize viral hepatitis due to hepatitis C were followed prospectively in 84 individuals treated with alpha-Interferon. In addition, the liver histology and the hepatic iron content of these same individuals, prior to the initiation of Interferon therapy, were determined. RESULTS: Patients not responding to the interferon therapy showed an increase in liver iron content from an average of 337 micrograms/g wet weight. In responder to a value of 1075 micrograms/g wet weight in non responders. gamma-glutamyl transpeptidase levels in responders were significantly lower than in partial or non-responders. CONCLUSIONS: Both the hepatic iron content of the liver and the gamma-glutamyl transpeptidase value prior to treatment were able to predict a clinical response to Interferon therapy. More importantly, the gamma-glutamyl transpeptidase level measured in serum could be used to monitor the IFN response during treatment and was found to predict clinical exacerbations of hepatitis following withdrawal of Interferon therapy.

Adult↗

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Interferon alpha treatment of chronic hepatitis C in patients with evidence for co-existent autoimmune dysregulation.

BACKGROUND/AIMS: We performed a prospective nonrandomized clinical trial to demonstrate that Interferon (IFN) treatment of individuals with chronic hepatitis C virus (HCV) positive hepatitis (CH-C) and serologic and/or histologic evidence of autoimmune dysregulation is feasible and whether the benefits of successfully treating CH-C are outweighed by the risk of exacerbating Autoimmune Chronic Active Hepatitis (ACAH). PATIENTS AND METHODS: 23 patients with positive autoimmune dysregulation markers underwent a 6 month course of IFN treatment for chronic HCV hepatitis and were followed for a total of 12 months. Patients were treated with 5 MU of a2b IFN administered subcutaneously 7 days a week for 6 months. Complete blood counts and a panel of liver enzymes were monitored weekly for 4 weeks and then monthly for an additional 11 months (6 months of therapy and 6 months of follow-up). Serum auto-antibodies titers were determined prior to treatment, at the end of the treatment and again after 6 months of follow-up. A liver biopsy was performed prior to, and at the end of treatment and again at 12 months. RESULTS: Using the standard ALT criteria for defining a response to IFN therapy, 14 (61%) patients experienced a full response and 3 (13%) experienced a partial response. Forty-three percent of the full responders and 33% of the partial responders experienced a relapse during the follow-up. The titer of each of the previously positive autoantibodies either remained unchanged or increased by 1 or 2 dilutions. No clinical exacerbations of a co-existent ACAH were observed. CONCLUSIONS: Individuals with combined CH-C and one or more markers of autoimmune dysregulation can be treated successfully with IFN. Such treatment does not necessarily increase or exacerbate co-existent ACAH and elevate the serum ALT level. In those who clear HCV-RNA as a result of IFN, the liver histology shifts from one consistent with CH-C to resembling ACAH.

Antiviral Agents↗

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Combination treatment of advanced HCV associated liver disease with interferon and G-CSF.

BACKGROUND/AIMS: Interferon (IFN) is the only therapy currently approved for chronic hepatitis C treatment. Unfortunately, not all patients respond to IFN therapy with a disease remission. Some people consider advanced histologic disease to be either a contraindication for treatment or a predictor of a poor response to treatment. To assess the validity of the two preceding widely held views, a total of 30 consecutive patients with advanced histologic disease associated with hepatitis C were studied. MATERIALS AND METHODS: Patients were treated with 5 million units of IFN administered SQ daily either alone or in combination with G-CSF (300 micrograms SQ on Mondays and Thursdays). RESULTS: Both groups responded to the IFN therapy with 53 and 60% respectively being HCV-RNA negative after 6 months of therapy and 40 and 53% respectively continuing as HCV-RNA negative after 6 months of follow-up after IFN. The mean white blood cell (WBC) count and peak WBC counts of those receiving G-CSF were greater than those not receiving G-CSF therapy. The nadir values for both groups, however, were similar. CONCLUSIONS: Based upon this study, utilizing daily high dose IFN (5 MU) therapy, it can be concluded that individuals with advanced histologic disease can be treated successfully with IFN and obtain a prolonged remission. The addition of G-CSF during IFN therapy of patients with histologically advanced disease increases the mean WBC and peak WBC count levels achieved during the course of IFN therapy but without significantly increasing the response rate defined as clearance of HCV-RNA at the end of treatment and follow-up.

Antiviral Agents↗

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Liver transplantation in Italy: preliminary 10-year report. The Monotematica Aisf-Olt Study Group.

Experience in liver transplantation (OLT) in Italy over a ten-year period is reported. Data were obtained using a multiple-items form collected from Italian liver transplant centres (reference centres) and other Italian institutions actively involved both in the processes of evaluation of the candidates and the follow-up of liver transplant recipients (afference centres). During this period, a total of 1046 liver transplants were performed on 954 patients, with a cumulative proportional survival of 71%. The most common indication for liver transplantation was post-hepatitic cirrhosis due to either hepatitis B virus (+/-hepatitis Delta virus) or hepatitis C virus infection. Good survival rates were observed, particularly in controversial indications, such as alcoholic cirrhosis, post-hepatitic hepatitis B virus-related cirrhosis and hepatocellular carcinoma, most likely due to proper and careful selection of the patients. Cirrhosis, secondary to an autoimmunity-based liver disease, showed the highest rate of rejection episodes. Infections, in our study population, were the most common cause of death after transplantation.

Adolescent↗

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Retreatment of hepatitis C interferon non-responders with larger doses of interferon with and without phlebotomy.

BACKGROUND/AIMS: Interferon a (IFN) is the only agent currently approved by the FDA for the treatment of chronic viral hepatitis due to hepatitis C (HCV). Unfortunately, less than half the patients with HCV treated with IFN respond. Worse yet, half or more of those who do respond relapse when the agent is withdrawn. MATERIALS AND METHODS: In this prospective randomized study, 30 individuals who had failed to respond to a standard course of IFN therapy consisting of 3 MU IFN administered 3 x week for 6 months were randomized to receive a second 6 month course of either 5 MU IFN daily or 5 MU IFN plus regular phlebotomies at weekly intervals to achieve a hemoglobin level of between 10-11 g/dl. The response rates defined as HCV-RNA negativity after 6 months of therapy and after 6 months of follow-up without IFN were determined. RESULTS: Both groups experienced a significant reduction in their serum ALT levels (p < 0.01) and Knodell scores with treatment. A greater number of responders were found in the phlebotomy plus IFN group than in the IFN alone group whether the response was defined by the serum ALT level or presence or absence of HCV-RNA in serum at the end of treatment and follow-up. CONCLUSIONS: The results of this study suggest that both an increased IFN dose coupled with more frequent dosing of IFN alone and combined with phlebotomy treatment are effective at obtaining a response to IFN in individuals with HCV disease who previously have failed to respond to a standard treatment regimen.

Female↗