Richard K. Gilroy

A multidisciplinary approach to the treatment of intestinal failure

Intestinal failure is most commonly treated by the administration of total parenteral nutrition (TPN). In some patients, however, surgical therapy may increase the ability to use the intestine for nutrition and thereby decrease the complications of TPN therapy. A multidisciplinary comprehensive intestinal failure program was initiated at the University of Nebraska Medical Center in October 2000. Here we describe the surgical approaches to patients with short bowel syndrome and the subsequent impact on the need for TPN and on survival. Fifty patients (children = 30, adults = 20) underwent surgical procedures to restore intestinal continuity (n = 5), repair enterocutaneous fistulas (n = 5), resect dysmotile or strictured/obstructed bowel segments or mesenteric desmoid tumors (n = 7), stricturoplasty (n = 2), Bianchi tapering and lengthening (n = 20), serial transverse enteroplasty (n = 8), and other operations (n = 8). Of these 50 patients, three patients did not require TPN after surgical intervention and seven had remnant small bowel anatomy that precluded TPN weaning (e.g., end duodenostomy) and were listed for transplantation or continued on full TPN support. Of the 40 remaining patients, most received the majority of calories fromTPNat the time of referral, i.e., mean calories fromTPN _ 90%. Subsequent to the surgical and medical therapy, 26 (65%) have been completely weaned off TPN. In addition, 10 had substantial decreases in their TPN requirements (i.e., from 85% of calories from TPN at onset decreased to a median 35% of required calories at most recent follow-up). Four patients remained on the same amount of TPN support. Four of the seven patients listed for transplantation underwent successful transplantation. Despite the complications of short bowel syndrome, 86% (n = 43) of the patients are alive and well at a mean follow-up of 2 years. Patient deaths occurred primarily in those listed or eligible for transplantation and were related to advanced liver disease (n = 3), gastrointestinal hemorrhage (n = 1), or line sepsis (n = 1). Two other patients died, one from influenza A infection and one from unknown cause at home, months after complete discontinuation of TPN. In this series of patients with short bowel syndrome, surgical intervention led to weaning or discontinuation of TPN support in 85% of patients. An organized multidisciplinary approach to the patient with short bowel syndrome is recommended.

Lipoatrophic diabetes and end-stage liver disease secondary to nonalcoholic steatohepatitis with recurrence after liver transplantation

Background. Lipoatrophic diabetes is an insulin resistance syndrome characterized by the complete or partial lack of adipose tissue and disturbances in lipid and glucose metabolism. Nonalcoholic steatohepatitis (NASH) is a well-described change in liver pathology consisting of steatosis, hepatitis, and fibrosis that can be associated with lipoatrophic diabetes. Results. This article describes the first reported case of lipoatrophic diabetes with NASH leading to liver failure and liver transplantation. Before transplantation, the patient required 600–700 U of insulin/day. After transplantation, a dramatic decline in her insulin requirements was observed, despite corticosteroids. Eighteen months after transplantation, her glycemic control worsened, and she developed recurrent NASH on serial liver biopsies. Conclusions. NASH associated with lipoatrophic diabetes can recur after liver transplantation, and in this case, was accompanied by increased insulin requirements. These results suggest that the development of NASH itself may contribute to the insulin resistance observed in lipoatrophic diabetes.

Pegylated interferon for recurrent hepatitis C in liver transplant recipients with renal failure: A prospective cohort study

Abstract Background Hepatitis C (HCV) universally recurs following orthotopic liver transplantation (OLT), representing an important cause for retransplantation. Although it is often treated with interferon and ribavirin, ribavirin is contraindicated in the presence of renal failure. In this setting of renal failure, pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients. Methods Between June 2001 and November 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment, end of treatment (EOT) and 6 months after EOT for those who were HCV-RNA negative at EOT. Patients were followed prospectively after starting weekly pegylated-interferon alpha 2b 1.0 μg/kg (Schering-Plough, Kenilworth, NJ, USA). Results Among the 45 patients with recurrent HCV screened, 9 were eligible, including 8 men and 1 woman of average age 55 years. Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months. Two patients developed a sustained response to HCV eradication. One patient who completed treatment has normal liver tests but is still viremic. Conclusion Pegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure. Larger, prospective studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life.

Mild donor liver steatosis has no impact on hepatitis C virus fibrosis progression following liver transplantation

Background: This study examines the impact of donor liver macrovesicular steatosis on recurrence of hepatitis C virus (HCV) disease after liver transplantation.

Outcomes of a patient-to-patient outbreak of genotype 3a hepatitis C†

Between March 2000 and July 2001, at least 99 persons acquired a hepatitis C virus genotype 3a (HCV‐3a) infection in an oncology clinic. This nosocomial HCV outbreak provided an opportunity to examine the subsequent clinical course in a well‐defined cohort. This was a retrospective/prospective observational study of the short‐term significant health outcomes of a large, single‐source, patient‐to‐patient HCV‐3a outbreak. Outbreak patients or their legal representatives consenting to study were enrolled between September 2002 and December 2007. We measured history and physical examinations, medical records, HCV serology, HCV RNA and genotype, liver enzymes, histology, response to antiviral therapy, and liver‐related morbidity and mortality. Sixty‐four of the 99 known HCV‐3a outbreak patients participated. During a 6‐year period, six patients developed life‐threatening complications from liver disease, three died, one received a liver transplant, and two were stable after esophageal variceal banding or diuretic therapy of ascites. Thirty‐three patients underwent antiviral therapy, with 28 achieving a sustained viral remission. One patient acquired HCV‐3a infection sexually from an outbreak patient and was successfully treated. Eleven study patients died of malignancy, including two that had achieved a sustained viral remission after antiviral therapy. Conclusion: Our patient cohort had a nosocomial source and an oncologic or hematologic comorbidity. Compared with previous HCV outcome studies, a patient‐to‐patient HCV outbreak in an oncology clinic exhibited significant morbidity and mortality. Attention is needed to the public health risk of nosocomial HCV transmission, emphasizing infection control, early diagnosis, and therapy. (HEPATOLOGY 2009.)

Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

Share 35 has us too wary of strangers bearing gifts.

In transplantation, physician behavior often changes in response to policy, and these shifts are often not considered when policies are developed. Some important examples include the number of recipients transplanted for hepatocellular carcinoma following initial implementation of Model for End-Stage Liver Disease (MELD) exceptions, the rise in the number of exception scores following the introduction of Share 15, and the decline in living donor pediatric kidney transplants following the prioritizing of deceased donors to younger recipients. Washburn et al., in this edition of Liver Transplantation, identify intended and unintended consequences of Share 35, a policy developed to enhance allocation of deceased donor organs to the sickest on the waiting list. Some unintended consequences following the implementation of Share 35 are quite evident but unexplained, like the decline in acceptance of organ offers to the sickest patients, ie, seeing that an organ offer made to the sickest patient is refused and how this offer goes to someone else lower on the list. The study only analyzes organ offers that were transplanted and does not provide data on the ultimate consequences of refused offers (MELD score and recipient age) and also important outcome details on the offer (survival, cost, or length of stay). Importantly, 50% of the refused offers to recipients with MELD >35 which were subsequently transplanted were initially declined for poorer donor quality. The frequency of declined offers increased following the implementation of Share 35. The authors suggest that the changes in acceptance patterns might reflect “better matching” of donors to recipients. The authors, however, provide no data to support this supposition. Indeed the donor risk index of 1.3 to the MELD >35 group remained unchanged during this period. A follow-up study of earlier work on wait-list mortality and survival benefit for high MELD candidates as suggested by the authors is clearly overdue. Another important and unanticipated change with Share 35 has been the rise in the absolute number of people waiting at a MELD score >35 despite an increase in the absolute number of people transplanted with a MELD score >35 (23.1%-30.1% of all transplants go to MELD >35). Data on declined offers also bring up an unsettling question: would a greater reduction in wait-list mortality, without compromise to utility, have occurred if the acceptance patterns stayed consistent across the eras of this study? Thus, although the goal was to reduce wait-list mortality by transplanting more of the sickest, we have listed and maintained more people with a MELD score of 35 and allowed fewer of the allocated offers to go to them, which is alarming when one notes that the median MELD score for this sickest population was approximately 40. The variability among United Network for Organ Sharing regions in the decision to accept offered organs is not explained in this study. Furthermore, acceptance rates of offered organs by region was not limited to marginal recipients (MELD >35) as variability in refused organs ultimately transplanted occurred in both the very high and lower MELD categories. We also lack data on the outcome of the recipient in whom the offer was

Pegylated-interferon for recurrent hepatitis C in liver transplant recipients with renal failure

BACKGROUND Hepatitis C (HCV) universally recurs following orthotopic liver transplantation (OLT), representing an important cause for retransplantation. Although it is often treated with interferon and ribavirin, ribavirin is contraindicated in the presence of renal failure. In this setting of renal failure, pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients. METHODS Between June 2001 and November 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment, end of treatment (EOT) and 6 months after EOT for those who were HCV-RNA negative at EOT. Patients were followed prospectively after starting weekly pegylated-interferon alpha 2b 1.0 microg/kg (Schering-Plough, Kenilworth, NJ, USA). RESULTS Among the 45 patients with recurrent HCV screened, 9 were eligible, including 8 men and 1 woman of average age 55 years. Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months. Two patients developed a sustained response to HCV eradication. One patient who completed treatment has normal liver tests but is still viremic. CONCLUSIONS Pegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure. Larger, prospective studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life.

An unusual cause of acute hepatitis

Purpose: Hepatitis C is a common cause of chronic liver disease but is rarely associated with acute hepatitis. Sexual transmission of hepatitis C is also uncommon and probably accounts for less than 5% of cases. We describe an unusual case of acute hepatitis C in a previously healthy patient who acquired the infection from her husband who had undergone a liver transplant for hepatitis C.