Mortality while awaiting liver retransplantation: predictability of MELD scores.

INTRODUCTION: Model for End-stage Liver Disease (MELD) scores at the time of listing on the transplant waiting list have been shown to accurately predict 3-month mortality in adults. There is no data assessing the accuracy of the MELD scores in predicting mortality of patients awaiting liver retransplantation. We sought to determine the outcome of patients listed for retransplantation at a single center and the accuracy of MELD scores in predicting mortality on the transplant waiting list. METHODS: A retrospective review of adult patients at a single center listed for a second liver transplantation during the years 1993 to 2000. MELD scores and a concordance statistic were calculated at the time of initial listing and initial transplant as well as the time of relisting for a second transplant and at 2, 4, 6, 8, 12, and 24 weeks after relisting. RESULTS: Of the 63 patients in the study, 43 (68%) received a second transplant, and 20 (32%) died while awaiting retransplantation. Of the patients receiving a second transplant, 13 (30%) died within 1 year of receiving the transplant. The most common cause of death on the waiting list was sepsis (50%), hepatorenal syndrome (20%), and multiorgan failure (10%), whereas the majority of deaths posttransplantation were sepsis-related (69%). At the time of relisting the c-statistic for MELD scores predicting death after 1 week on the waiting list was 0.78 (P = .007). After 3 months on the waiting list, the c-stat was largely unchanged (0.76, P = .04). CONCLUSIONS: We have shown that MELD scores may predict mortality on the transplant waiting list for patients listed for a second transplant.

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

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.

Posttransplantation care: role of the primary care physician versus transplant center.

1. Forty percent of transplant centers expect the primary care physician to be the primary physician; 40% have both a primary care physician and a hepatologist manage the patient. 2. Transplant centers expect primary care physicians to provide general preventive medicine, physical examinations, vaccinations, and, rarely, management of hypertension, renal dysfunction, and diabetes. 3. A high percentage of primary care physicians feel comfortable caring and managing the overall health care of a long-term liver transplant patient. 4. Primary care physicians feel at most ease managing preventive care, annual physical examinations, hypertension, diabetes mellitus, hyperlipidemia, bone disease, and vaccinations. 5. Primary care physicians should be aware of the common medical conditions of the liver transplant patient of hypertension, diabetes, obesity, hyperlipidemia, and recurrent disease. 6. Common medical conditions for both the transplant centers and primary care physicians are hypertension, dyslipidemia, diabetes mellitus, malignancy, bone disease, pregnancy, vaccination, infectious prophylaxis, and headaches.

Gender differences in colorectal polyps and tumors.

OBJECTIVES: To use a national endoscopy database (CORI) to determine 1) whether gender differences are noted in the prevalence and location of polyps and tumors; 2) whether women have a higher rate of right-sided polyps or tumors; and 3) whether age influences these results. METHODS: CORI database from April 1, 1997 to February 19, 1999, captured in a computer-generated report, was analyzed. Polyps for this study were defined as sessile or pedunculated and as >9 mm. Tumors were defined as lesions characteristic of adenocarcinoma (mass, apple-core). Pure right-sided colon (PRS) was defined as cecum, ascending, hepatic flexure; right-sided as PRS plus the transverse colon; and left-sided as the splenic flexure, descending, sigmoid and rectum. RESULTS: Men have a greater risk of polyps [odds ratio (OR), 1.5] and tumors (OR, 1.4) than women. The risk of finding polyps and tumors at colonoscopy increases with age, with the highest risk noted in those >69 yr of age relative to patients <50 yr of age (polyps, OR = 2.7; tumors, OR = 4.0). Right-side polyps and pure right-sided polyps as defined by the study design were noted to be more frequent than left-sided polyps in patients >60 yr of age. Women have a greater risk of developing pure right-sided polyps (OR, 1.2), tumors (OR, 1.6) and right-sided tumors (OR, 1.5) than men. CONCLUSIONS: Men have a higher prevalence of colon polyps and tumors than women. A progressive risk of polyp or tumor formation is noted with aging. Women had a greater number of pure right-sided polyps and tumor development. Colonoscopy is needed to correctly diagnose an increasing prevalence of right-sided pathology in the elderly.

Isolated intestinal transplantation for intestinal failure.

OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal failure. However, some experience life-threatening complications from parenteral nutrition, and in these individuals intestinal transplantation may be lifesaving. METHODS: This is a retrospective review of 28 consecutive isolated small bowel transplants performed in eight adults and 20 children between December 1993 and June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient and graft survivals were 93% and 71%, respectively. The causes of graft loss were hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n = 1), and patient death (n = 1). The median length of time required until full enteral nutrition was 27 days. All 28 patients have experienced acute rejection of their small bowel grafts and rejection led to graft failure in five. Jaundice and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and hyperbilirubinemia was completely reversed in all patients with functional grafts within 4 months of transplantation. Three patients developed post-transplant lymphoproliferative disease (11%). Three recipients developed cytomegalovirus enteritis and all were successfully treated. CONCLUSIONS: Patient survival after intestinal transplantation is comparable to parenteral nutrition for patients with intestinal failure. Better immunosuppressive regimens are needed to decrease the risk of graft loss from acute rejection. The incidence of posttransplant lymphoproliferative disorder is higher after intestinal transplantation than after other solid organ transplants and the risk of cytomegalovirus enteritis is low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the absence of established cirrhosis can be reversed.

Pneumococcal vaccine response in cirrhosis and liver transplantation.

Cirrhosis is a major risk factor for severe pneumococcal infection, and patients evaluated for liver transplantation routinely receive pneumococcal vaccine. This study followed serologic antibody levels of 45 adults evaluated for transplantation and 13 age-matched control subjects. All received 23-valent pneumococcal polysaccharide vaccine (PPS). Serum anti-PPS levels and antibodies specific for capsular types 3 and 23 were measured by ELISA before and 1 and 6 months after vaccination. Antibody levels for the 25 patients who received transplants also were measured immediately before and 3 months after transplantation. Control subjects had higher IgG responses to the whole vaccine, whereas patients appeared to produce more IgM and IgA. IgA, and possibly IgM levels, also declined faster in patients than in control subjects. All anti-PPS levels were at or below prevaccination baselines by 3 months after transplantation. These data suggest that vaccination with PPS may not be effective for patients during and after liver transplantation.

Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case-control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7-year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child-Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04-8.3). Serum carbohydrate antigen 19-9 (CA 19-9) was significantly higher in patients with CCA than those without (177 +/- 89 and 61 +/- 58 U/mL, respectively; P =.002). A serum CA 19-9 level > 100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19-9 appeared to have good ability to discriminate PSC patients with and without CCA.

Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. The Acute Liver Failure Study Group.

Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

Long-term follow-up after liver transplantation in patients with hepatic iron overload.

Patients with hepatic iron overload who undergo orthotopic liver transplantation (OLT) have a worse 1-year survival than those who undergo transplantation for other indications; the long-term outcome in this population is unknown. The purpose of this study is to report long-term follow-up after OLT in a cohort of patients with hepatic iron overload. Five liver transplant centers in the United States reported follow-up data on 37 patients receiving a first liver transplant who had severe hepatic iron overload in their native livers. Kaplan-Meier 5-year survival among these patients was compared with survival data from all age-matched liver transplantations reported to the United Network for Organ Sharing (UNOS) over the same time period (1987 to 1993). The 5-year survival rate after OLT was 40% in the hepatic iron overload group compared with an overall survival rate of 62% for all patient groups from the UNOS registry (P =.0009). Although sepsis was the cause of 53% of all deaths occurring within the first year after OLT, cardiac complications accounted for 50% of the late mortality in patients with hepatic iron overload. In conclusion, long-term survival after OLT is significantly decreased in patients with hepatic iron overload. Infectious and cardiac complications are the most common causes of death in these patients. Further studies are needed to define the relationship between hepatic iron overload and mortality and to examine the effect of iron depletion on outcome after OLT in this patient population.

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Heterozygous alpha 1-antitrypsin phenotypes in patients with end stage liver disease.

OBJECTIVE: The objective of the study was to determine the prevalence and associations of abnormal alpha1-antitrypsin phenotypes in Caucasian adults with end stage liver disease with particular emphasis on heterozygous phenotypes and disease from hepatitis C virus. METHODS: All patients (788) with end stage liver disease considered for liver transplantation from July 1990 to June 1996 in a referral-based university hospital transplant center (University of Nebraska Medical Center, Omaha, NE) comprised the study population. Data for the study population was determined by retrospective review of the transplantation database at the transplant center. Hepatitis C virus infection was determined by a second generation ELISA method, and alpha1-antitrypsin phenotyping was performed on agarose gel with serum quantitation using a Behring Nephelometer. RESULTS: Among 683 Caucasian patients with severe liver disease, the prevalences of Pi ZZ, Pi MZ, and Pi MS were 0.4, 7.3, and 8.2%, respectively, compared with 0, 2.8, and 4.2% in the control population. The odds of having a heterozygous Z phenotype were significantly increased in Caucasian patients with hepatitis C virus (odds ratio (OR) = 4.3, 95% confidence interval (CI) = 2.1-9.0), alcoholic liver disease (OR = 5.0, 95% CI = 2.6-9.6), primary hepatic malignancy (OR = 7.4, 95% CI = 2.9-19.0), and cryptogenic cirrhosis (OR = 2.6, 95% CI = 1.1-6.3) compared with the control population. Caucasian patients with hepatitis C or B virus were 3.6 times more likely to have a heterozygous Z phenotype than a normal phenotype compared with patients with diseases of autoimmune etiology. CONCLUSION: This study provides evidence of an association of heterozygous Z alpha1-antitrypsin phenotype with end stage liver disease of several etiologies, not hepatitis C virus alone.

The American experience with transplantation for acute liver failure.

Liver transplantation has become the major therapy for acute liver failure (ALF) in the United States. Survival rates range from 46% to 89%. Appropriate patient selection, timely referral, and management of common complications have improved survival. Donor organ shortage may prompt further use of extracorporeal support systems and auxillary transplantation in the future. This article reviews the American experience of liver transplantation in patients with ALF.

Attitudes and expectations of 1995 gastroenterology graduates about gastroenterology.

OBJECTIVE: To learn more about current attitudes and expectations of recent (June 1995) graduates of gastroenterology fellowship programs, why they chose either a private practice or academic career, and what impact managed care or health care reform had in their decision. METHODS: Between April and June 1995, and 8-page, 35-question survey questionnaire was mailed to graduating fellows and returned for evaluation. RESULTS: Graduates believed managed care had an impact on job availability, but it was not a factor in their job choice. Forty percent of the respondents reported that finding a job was either difficult or very difficult. The majority of respondents (67%) are pursuing a career in private practice. Most private practice physicians (PP) trained in 2-yr programs whereas academic physicians (AC) trained for the most part in 3-yr programs. The principal criteria on which decisions regarding job selection were based were similar between the two groups: co-workers, geographic location, access to patient care, and ability to perform endoscopy. Respondents in PP and AC expected to work 50-70 h/wk, care for patients with similar diseases, and have ample time for family. They would choose GI again as a career and believed that there is a future in GI. Salary expectations varied markedly between the two groups, and AC physicians were more concerned about their future financial needs. Twenty percent of PP physicians and 71% of AC physicians plan to participate in clinical research. CONCLUSIONS: Recent graduates of gastroenterology fellowship programs continue to have high expectations of their future careers. Although some had difficulty finding a job and stated that, although managed care had an impact on the job market, it had not yet become a major factor in their job selection.

Morbidity in patients with posttransplant diabetes mellitus following orthotopic liver transplantation.

It is not well understood whether posttransplant diabetes mellitus (PTDM) following orthotopic liver transplantation (OLTx) alters postoperative morbidity. This study was designed to evaluate this question. All adult patients who received an OLTx between July 1985 and March 1993 (n = 497) were evaluated by retrospective chart review for evidence of PTDM after OLTx. The patients identified with PTDM (n = 26) were case matched with nondiabetic OLTx recipients based on primary liver disease diagnosis, age, gender, date of first OLTx, and survival. Liver synthetic function, number and severity of rejection episodes, graft survival, total number of hospital days within the first year post-OLTx, renal function, and number and type of infection episodes were analyzed to assess differences in morbidity between the PTDM and control patients after OLTx. Of the 497 adult patients who underwent OLTx, 26 (5.2%) were identified as having PTDM within 1 month of discharge. Factors which identified individuals at higher risk for DM after OLTx included higher pre-OLTx fasting blood glucose (P = .04); lower body mass index after OLTx (P = .02); and cyclosporine rather than OKT3 induction (P = .009). Graft survival, synthetic function, and the total number of rejection episodes during the first year were not different between the two groups. The morbidity variables of total number of days in the hospital during the first 12 months, renal function, and type and number of infections were also similar between the two groups. In summary, 5.2% of adult patients developed DM within 1 month of OLTx. Pre-existing insulin resistance, postoperative stress, and immunosuppression medications all likely contribute to the development of overt hyperglycemia after OLTx. Although PTDM can be a consequence of OLTx, it does not have a significant impact on patient outcome in the first year after OLTx.

Low incidence of intraspousal transmission of hepatitis C virus after liver transplantation.

Although the incidence of spousal transmission of hepatitis C virus (HCV) in chronic carriers is extremely low (1.4% to 8%), hepatitis C recurrence after liver transplantation is common with markedly increased serum HCV RNA levels. Thus, partners of these patients may be at higher risk of acquiring infection. This study evaluates the prevalence of spousal transmission of hepatitis C after liver transplantation. Twenty-two of 25 couples who were eligible agreed to the retrospective study. Twenty-two patients (17 males, 5 females) and spouses (5 males, 17 females) were studied with respective mean ages of 50.2 years (35 to 65 years) and 46.9 years (33 to 66 years). Liver enzymes, second-generation enzyme-linked immunosorbent assay (ELISA) for antibody to HCV (anti-HCV) and HCV RNA by polymerase chain reaction (PCR), and branched DNA assay were performed. HCV-associated antibodies were detected in 1 of 22 (5%) spouses and 21 of 22 (95%) patients (P < .0001). Nineteen of 22 (86%) patients tested positive by PCR with a mean value of 16,218,100 Eq/mL (464,700 to 51,980,000). All spouses including the only ELISA anti-HCV positive spouse tested negative by PCR (P < .0001). Eight of 21 spouses tested negative for anti-HCV pretransplantation, (13 of 21 pretransplantation were not tested). Estimated mean duration of hepatitis C infection in patients was 14 years (3 to 40 years). Mean patient follow-up posttransplantation was 654.5 days (141 to 1,959 days). Mean duration of marriage was 22.6 years (2.5 to 46 years). No risk factors other than exposure to index patients were observed in spouses. The incidence of spousal transmission of HCV in liver transplantation remains low (5%) and similar to chronic carriers of HCV.