Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes.

OBJECTIVES: The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival. METHODS: North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival. RESULTS: 653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality. CONCLUSIONS: Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.

A randomized, placebo-controlled study of the NS5B inhibitor beclabuvir with peginterferon/ribavirin for HCV genotype 1.

Beclabuvir is a potent, non-nucleoside inhibitor of the HCV NS5B RNA polymerase, with nanomolar activity against HCV genotypes 1, 3, 4, 5 and 6 in vitro. This study evaluated the efficacy and safety of beclabuvir, in combination with peginterferon alfa-2a (pegIFN) and ribavirin (RBV), in HCV genotype 1. In this randomized (1:1:1), double-blinded, placebo-controlled, dose-ranging phase 2a study, 39 treatment-naive patients chronically infected with HCV genotype 1 were treated for 48 weeks with beclabuvir (75 mg or 150 mg) plus pegIFN (180 µg) and RBV (1000 mg/day [<75 kg] or 1200 mg/day [≥ 75 kg]) vs pegIFN/RBV alone. The primary efficacy endpoint of extended rapid virologic response (undetectable HCV RNA at treatment weeks 4 and 12) was achieved by 76.9% (10/13) of patients receiving beclabuvir 75 mg and 38.5% (5/13) receiving beclabuvir 150 mg vs 0% receiving pegIFN/RBV alone. Higher response rates were observed among patients receiving beclabuvir 75 mg for all secondary efficacy endpoints, including sustained virologic response at follow-up weeks 12 or 24. Three patients experienced virologic breakthrough on treatment, all in the beclabuvir 150-mg treatment group. Beclabuvir was well tolerated at both doses, with the most commonly observed adverse events (headache, fatigue, nausea, decreased appetite, irritability, depression and insomnia) consistent with those observed with pegIFN/RBV. In conclusion, beclabuvir was both effective and well tolerated when administered in combination with pegIFN/RBV for the treatment of chronic HCV GT 1, supporting the study of beclabuvir as part of an all-oral regimen for HCV GT1.

Liver transplantation in the United States, 1999-2008.

Changes in organ allocation policy in 2002 reduced the number of adult patients on the liver transplant waiting list, changed the characteristics of transplant recipients and increased the number of patients receiving simultaneous liver-kidney transplantation (SLK). The number of liver transplants peaked in 2006 and declined marginally in 2007 and 2008. During this period, there was an increase in donor age, the Donor Risk Index, the number of candidates receiving MELD exception scores and the number of recipients with hepatocellular carcinoma. In contrast, there was a decrease in retransplantation rates, and the number of patients receiving grafts from either a living donor or from donation after cardiac death. The proportion of patients with severe obesity, diabetes and renal insufficiency increased during this period. Despite increases in donor and recipient risk factors, there was a trend towards better 1-year graft and patient survival between 1998 and 2007. Of major concern, however, were considerable regional variations in waiting time and posttransplant survival. The current status of liver transplantation in the United States between 1999 and 2008 was analyzed using SRTR data. In addition to a general summary, we have included a more detailed analysis of liver transplantation for hepatitis C, retransplantation and SLK transplantation.

Endoscopic retrograde cholangiopancreatography, but not esophagogastroduodenoscopy or colonoscopy, significantly increases portal venous pressure: direct portal pressure measurements through endoscopic ultrasound-guided cannulation.

BACKGROUND AND STUDY AIMS: Changes in portal pressure during endoscopy have not been previously evaluated. The aims of this study were to assess the effect of esophagogastroduodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) on portal vein, inferior vena cava (IVC), and systemic pressures. PATIENTS AND METHODS: Five acute experiments were performed on 50-kg pigs utilizing endoscopic ultrasound (EUS)-guided catheterization of the portal vein and IVC. Systemic, intra-abdominal, IVC, and portal vein pressures were monitored during colonoscopy, EGD, and ERCP with endoscopic sphincterotomy. After endoscopy the animals were sacrificed for necropsy. The main outcome measure was pressure change during each type of endoscopic procedure. RESULTS: There were no significant changes in heart rate or systemic pressure during all endoscopic procedures. Intra-abdominal pressure increased during colonoscopy ( P = 0.02) and ERCP ( P = 0.007). However, mean portal venous pressure was significantly elevated only after the injection of contrast into the common bile duct, reaching its peak value at the time of biliary sphincterotomy (39.0 +/- 15.2 mm Hg vs. 13.4 +/- 3.6 mm Hg at baseline, P = 0.006). Mean peak IVC pressure was also elevated during ERCP, but it did not reach statistical significance (24.0 +/- 10.7 mm Hg vs. 12.6 +/- 4.1 mm Hg at baseline, P = 0.06). CONCLUSION: EGD and colonoscopy did not cause significant changes in portal vein, IVC, or systemic pressures. ERCP with biliary sphincterotomy increased portal pressure with only limited effect on IVC and systemic pressures. These new data indicate a possible connection between ERCP with sphincterotomy and portal pressure, and may be clinically important for patients with liver disease and other causes of portal hypertension who undergo this procedure.

Endoscopic ultrasound and fine needle aspiration for the diagnosis of hepatocellular carcinoma.

Liver cancer is one of the most frequent solid cancers. The major risk factor associated with the development of hepatocellular carcinoma (HCC) is cirrhosis caused by hepatitis B, hepatitis C virus or chronic alcohol consumption. The overall prognosis of patients with HCC is very poor and this is mainly due to the advanced stages of cancer at presentation and also because of underlying cirrhosis. When HCC is diagnosed at early stages, prognosis is better with five-year disease free survival of around 50% with resection, or local ablative treatments such as radio-frequency ablation or percutaneous ethanol injection, and 70-80% with liver transplantation. Therefore, systematic screening of all the high-risk patients is the key to an early diagnosis of small HCC and the use of an appropriate treatment modality. The currently available tools for the screening, surveillance and diagnosis of HCC in the presence of cirrhosis remain sub-optimal. The advancements made in the past 10 years, however, have made HCC a potentially curable disease in a highly selected group of patients. This review will briefly discuss the current guidelines for surveillance and diagnosis of HCC in high-risk subjects and then review the potential role of endoscopic ultrasound and fine needle aspiration for the diagnosis of small HCC.

Effect modification in liver allografts with prolonged cold ischemic time.

Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.

Endoscopic frontiers in the field of hepatology.

Hepatology is considered a cognitive specialty, but it will not be surprising if a subgroup of future hepatologists (''invasive hepatologists'') performed a variety of advanced endoscopic, laparoscopic, vascular or ablative procedures just like interventional gastroenterologists, interventional radiologists or minimally invasive surgeons. The increase in the prevalence of liver diseases including hepatocellular carcinoma, and effective treatment of end-stage liver disease with liver transplantation has expanded the subspecialty of hepatology into a major specialty. Therefore, it is only natural that some of the trainees in hepatology, familiar with invasive procedures just like their counterparts in gastroenterology, may become subspecialized in invasive aspects of this specialty, traditionally performed by interventional endoscopists, radiologists and surgeons. Moreover, there will be major developments in the management of the complications of liver disease. Endoscopic screening with esophageal capsule endoscopy and, to a lesser extent, ultrathin upper gastrointestinal endoscopy may replace conventional endoscopy. In addition to standard treatments for esophageal varices, removable esophageal stents with expansile pressure may be utilized in refractory variceal hemorrhage. Transjugular intrahepatic portosystemic shunts may be performed by hepatologists. Advances in argon plasma coagulation, cryotherapy and photodynamic therapy may result in novel treatment options for portal hypertensive gastropathy. Single-fiber cholangioscopy will allow for directed endoscopic screening for cholangiocarcinoma and primary sclerosing cholangitis in high-risk individuals. Minilaparoscopy will allow a macroscopic assessment of the liver surface as well as the ability to target specific regions for histopathology, and treatment including radiofrequency ablation of liver cancer. Endoscopic ultrasound (EUS) may provide the potential to directly measure portal vein pressure and this may have a future role in titration and optimization of pharmacological therapy of portal hypertension. EUS and fine needle aspiration may be used for staging hepatocellular and bile duct cancer. Finally, natural orifice transluminal surgery and endoscopic ultrasound-guided angiography may allow for targeted therapies traditionally outside the realm of the hepatologists.

Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites: a randomized, double-blind, placebo-controlled, single ascending dose study.

BACKGROUND: RWJ-351647 is a selective V2 receptor antagonist that inhibits vasopressin-induced water reabsorption in the kidney. AIM: To investigate the safety and tolerability of RWJ-351647 compared with placebo after single oral dose administration to patients with cirrhosis and ascites, on a stable treatment with furosemide and spironolactone. METHODS: Single oral doses of 1, 2 and 5 mg of RWJ-351647 were administered to 24 patients with ascites on stable concomitant diuretic treatment. RESULTS: RWJ-351647 had a tmax of 1 to 1.1 h and mean half-life of 10.4-17.4 h. There was no affect on the pharmacokinetics of concomitant diuretics. Increases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose-dependent manner reaching the statistical significance at the 5-mg dose. Four patients exhibited a decrease of > 2 kg in weight in the 24 h after dosing. RWJ-351647 was well tolerated, with no evidence of a dose-related increase in adverse events when compared with placebo. No changes in either serum chemistry or plasma AVP (arginine vasopressin) and renin levels were observed despite the observed aquaresis. CONCLUSION: RWJ-351647 is an effective aquaretic causing dose-dependent increases in urine output and free water clearance, when co-administered with conventional diuretics in patients with cirrhosis and ascites.

Biliary complications after liver transplantation: the role of endoscopy.

Biliary complications are important causes of early and late postoperative morbidity and mortality after liver transplantation and are seen in 10-20 % of the patients. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures. Less common complications are hilar strictures, intrahepatic strictures, and papillary stenosis/dysfunction. The complications are similar in living-donor and cadaveric liver transplantations, except for a higher incidence of bile leaks among living-donor transplant recipients. The clinical presentation of post-liver transplant bile duct complications is often subtle, and noninvasive imaging studies may sometimes fail to detect mild but clinically significant stenoses or small leaks. Early recognition and prompt treatment of biliary complications following liver transplantation reduces the morbidity and improves long-term graft and patient survival. In this report, we discuss the role of endoscopy in the diagnosis, treatment options, and the outcome for patients with biliary complications following liver transplantation.

Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C.

BACKGROUND AND AIM: In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment naïve patients with chronic hepatitis C virus (HCV). METHODS: In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment. RESULTS: At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects. CONCLUSION: Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.

Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma.

PURPOSE: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured < or = 7 cm, total tumor volume < or = 200 cm(3)). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. RESULTS: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. CONCLUSION: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Prolonged QTc interval and its relationship to autonomic cardiovascular reflexes in patients with cirrhosis.

BACKGROUND/AIMS: We have previously shown that an abnormality in cardiac autonomic reflexes (AN) is an independent predictor of mortality in patients with chronic liver disease. Aim of this study was to determine whether there was an association between prolonged QTc interval and cardiac AN. METHODS: Cardiac AN and QTc interval were determined in 130 patients (Child A 42, B 53, C 35) with alcoholic and non-alcoholic liver disease. RESULTS: Prolonged QTc (>440ms) was seen in 58 (Child A 30%, B 46%, C 60%, P=0.04) patients. Autonomic tests were normal in 21%, borderline abnormal in 36% and definitely abnormal in 43%. QTc correlated with albumin (P<0.001), prothrombin time (P=0.003) and Child-Pugh score (P<0.001), but not with Valsalva ratio, heart rate variation with 6 breath/min breathing, tilt table or isometric exercise. By logistic regression analysis, QTc correlated only with Child-Pugh score (P<0.001). Mean QTc of 34 who died during the follow up was higher than survivors. Cox regression analysis showed that only Child-Pugh score and AN were independent predictors of mortality. CONCLUSIONS: Prolonged QTc seen in liver disease is independent of their cardiac autonomic function, but is related to the severity of the liver disease.

Outcome of liver transplantation in patients with diabetes mellitus: a case-control study.

The influence of preexisting diabetes mellitus (DM) on outcome after orthotopic liver transplantation (OLT) has not been well defined. The objective of our study was to compare the morbidity and mortality after OLT in 57 patients with preexisting DM (3 type I, 54 type II) with 114 age-, sex-, and race-matched patients without DM (case controls). The demographics were similar in both groups. Pretransplantation serum creatinine was significantly higher in the diabetic group compared with case controls. The incidence of the following complications was significantly higher in the diabetic group after OLT: cardiovascular (61.4% vs. 21.9%, P <.001), major (54.4% vs. 29.8%, P =.002) and minor infections (29.8% vs. 7.9%, P <.0001), renal (59.7% vs. 20.2%, P <.001), ophthalmologic (10.5% vs. 0.9%, P =.01), respiratory (24.6% vs. 7.0%, P =.001), neurologic (31.6% vs. 7.0%, P <.001), hematologic (19.3% vss 2.6%, P =.001), musculoskeletal (24.6% vs. 5.3%, P =.001), and malignancy (22.8% vs. 10.5%, P =.03). The duration of hospital stay, cost of hospitalization, retransplantation, and overall graft survival were similar. Acute rejection was seen in 50.9% of diabetics compared with 25.4% in controls (P =.0009). One-year (87% vs. 77%) and 2-year (81.6% vs. 70.1%) patient survival was similar, but 5-year survival was lower in the DM group (34.4% vs. 67.7%, P =.002). In conclusion, preexisting diabetes is associated with a significant post-OLT morbidity and mortality, and our observations suggest that patients with DM warrant more rigorous pre- and post-OLT evaluation.

Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.

Human monocytic ehrlichiosis: an emerging pathogen in transplantation.

BACKGROUND: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

Spontaneous bacterial peritonitis--in-hospital mortality, predictors of survival, and health care costs from 1988 to 1998.

OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a complication of end-stage liver disease with a reported mortality of 30-50%. In this study, we investigated the outcome of all patients admitted to Maryland hospitals with SBP from 1988 to 1998. Main outcomes considered included trends in survival rates over time, changes in the length of stay, total health care costs, and variables that predicted survival rates. METHODS: We used the Maryland Health Services Cost Review database of all patients admitted to Maryland hospitals with an International Classification of Diseases (Ninth Revision) code for both peritonitis and cirrhosis from 1988 to 1998. RESULTS: A total of 348 patients were admitted with an in-hospital mortality of 32.6%; there was no significant change in mortality rate during this period. The survival rate was similar in the university and community hospitals. In the logistic regression analysis, age (p = 0.001) and intensive care unit stay (p = 0.0001) were found to significantly influence the survival rates; those patients who had an intensive care unit stay were 2.8 times more likely to die than those who did not have an intensive care unit stay, controlling for age. The average length of hospital stay remained unchanged (13.5 +/- 12.7 days) during the study period. Although the median hospital charge (excluding professional fees) remained unchanged, mean inflation-adjusted charges increased from $7,897 in 1988 to $25,902 in CONCLUSIONS: The mortality rate associated with SBP has remained unchanged over an 11-yr period from 1988 to 1998. The mortality showed a strong correlation with age and intensive care unit stay. The median hospital stay and median charges remained unchanged during this period, but mean costs increased significantly because of increased use of resources by a few patients.

Autonomic dysfunction and cholelithiasis in patients with cirrhosis.

Gallstones are seen in 33-46% of patients with cirrhosis, and their prevalence is known to increase with the duration and severity of liver disease. We hypothesized that autonomic neuropathy may contribute to the formation of gallstones or gallbladder disease, as in diabetics with autonomic neuropathy, due to impaired gallbladder emptying. The objective of our study was to determine the prevalence of gallstones or gallbladder disease in cirrhotic patients with and without autonomic neuropathy. We determined autonomic function tests, gallstones, and other gallbladder disease in 123 (male 71) with varying severity of liver disease (Child classes: A, 40; B, 45; C, 35). In all, 54 patients had gallstones and an additional 22 patients had other gallbladder disease (cholecystitis, common bile duct stones, or debris). Autonomic neuropathy was seen in 97 patients (one abnormal test in 48 and two or more in 49). The prevalence of gallstones was similar in Child A (57%), Child B (64%), and Child C (63%) cirrhosis. The gallstones or gallbladder disease was not increased in women, blacks, diabetics, or alcoholic cirrhotics. The prevalence of gallbladder disease was increased in patients with autonomic neuropathy (51% vs 35%, P = 0.08); in patients with Child C cirrhosis, gallstones (P = 0.018) and gallbladder disease (P = 0.03) were seen more commonly in patients with autonomic neuropathy. Our findings suggest that autonomic neuropathy may contribute to the formation of gallstones in patients with advanced cirrhosis, perhaps by impairing gallbladder and sphincter of Oddi dysmotility.

Recurrent, progressive giant cell hepatitis in two consecutive liver allografts in a middle-aged woman.

In this report, we present a 41-year-old woman who developed rapidly progressive "giant cell hepatitis" that lead to end-stage liver disease. She underwent a successful liver transplantation in 1989. However, the giant cell hepatitis recurred in the allograft, resulting in cirrhosis within 4 years. She underwent a second liver transplantation in 1993. After 2 years of a relatively stable course, she again developed cirrhosis and was awaiting liver transplantation at the time of this report. The histopathologic features in the two allografts were identical to her original disease. Despite extensive investigations, no etiology for her liver disease could be found.