Malignant infiltration of the liver presenting as acute liver failure.

There have been few reports of acute liver failure (ALF), with encephalopathy and coagulopathy, caused by infiltration of the liver by malignant cells. We describe a case series of 27 patients with ALF caused by malignancy. We examined a large, multicenter ALF registry (1910 patients; mean age, 47.1 ± 13.9 y) and found only 27 cases (1.4%) of ALF attributed to malignancy. Twenty cases (74%) presented with abdominal pain and 11 presented with ascites. The most common malignancies included lymphoma or leukemia (33%), breast cancer, (30%), and colon cancer (7%); 90% of the patients with lymphoma or leukemia had no history of cancer, compared with 25% of patients with breast cancer. Overall, 44% of the patients had evidence of liver masses on imaging. Diagnosis was confirmed by biopsy in 15 cases (55%) and by autopsy for 6 cases. Twenty-four patients (89%) died within 3 weeks of ALF.

Capsule endoscopy is not as accurate as esophagogastroduodenoscopy in screening cirrhotic patients for varices.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is the standard technique for screening cirrhotic patients for high-risk varices and other significant upper gastrointestinal lesions (HRVLs). We investigated whether esophageal capsule endoscopy (ECE) is as convenient and accurate as EGD for the detection of HRVLs. METHODS: We analyzed data from 65 cirrhotic patients without prior upper gastrointestinal bleeding who were examined for varices and HRVLs by ECE and EGD (both procedures were performed on the same day). EGD was performed by 2 physicians (75% of patients were unsedated) who used standard grading for esophageal and gastric varices, portal hypertensive gastropathy, and HRVLs. Coded capsule tracings were read by 2 investigators, blinded to the EGD findings, using standard grading. RESULTS: The median procedure time for EGD (with or without biopsy collection) was 3 minutes, compared with 20 minutes for ECE. The overall accuracy for diagnosis of esophageal varices was 63.2% ± 5.9%; for detection of esophageal varices red marks was 68.8% ± 5.4%; and for diagnosis of other HRVLs was 51.5% ± 4.2%. The interobserver agreement in the diagnosis of esophageal varices was 90.8%; in the detection of esophageal varices red marks was 86.2%; and in the diagnosis of other HRVLs was 7.3%. CONCLUSIONS: ECE is not as accurate as EGD in the diagnosis of esophageal varices and red markings or in grading esophageal varices. Moreover, ECE had poor accuracy in grading portal hypertensive gastropathy and detecting ulcers, gastric varices, and other significant upper gastrointestinal lesions. It took significantly longer to perform ECE and interpret the results than for EGD. These findings do not support ECE as a preferred tool for screening esophageal varices and HRVLs.

Endoscopic treatment with multiple stents for post-liver-transplantation nonanastomotic biliary strictures.

BACKGROUND: Over the past decade, ERCP has become the preferred method of treatment for biliary strictures in patients after orthotopic liver transplantation (OLT). Although data strongly support ERCP for treating anastomotic strictures, the little information available for the role of ERCP in the treatment of nonanastomotic strictures (NAS) has been unpromising. OBJECTIVE: We investigated the efficacy and safety of using balloon dilation and multiple biliary stents to treat NAS. DESIGN: A retrospective study. SETTING: A tertiary-care medical center. PATIENTS: Fifteen patients who were diagnosed with post-OLT NAS between January 2003 and June 2007. INTERVENTIONS: ERCP with balloon dilation and multiple stenting. MAIN OUTCOME MEASUREMENTS: Resolution, complication, and recurrence rates. RESULTS: Eleven of the 15 patients completed endoscopic treatment, of whom 9 had cholangiographic improvement, biochemical normalization, and cholestatic symptom relief (treatment success), and 1 required retransplantation (treatment failure). None of the 9 successfully treated patients experienced NAS recurrence in a mean follow-up of 17 months. Of the remaining 4 patients, 1 died of nonbiliary causes and 3 were still undergoing treatment with stents in place, of whom 2 have near-normalized total serum bilirubin and were cholestatic symptom free. LIMITATIONS: A retrospective study, small sample size, single endoscopist. CONCLUSIONS: Endoscopic treatment of NAS with balloon dilation and multiple stents appears to be safe and effective, and it may reduce the need for retransplantation because of NAS. Larger studies are still required to confirm its utility as a mainstay for treating NAS and to determine what factors are associated with endoscopic treatment success.

Outcomes of patients with hepatitis B who developed antiviral resistance while on the liver transplant waiting list.

BACKGROUND & AIMS: Lamivudine has been shown to improve liver disease and survival of hepatitis B virus patients on the orthotopic liver transplantation (OLT) waiting list, but liver failure might worsen in patients with drug resistance. Use of antiviral salvage therapy might decrease this risk. METHODS: We analyzed data from patients enrolled in the NIH HBV OLT cohort to study the effects of pretransplant antiviral therapy on transplant-free survival and survival without transplant. We also compared the clinical outcomes of those who did or did not develop antiviral failure (virologic breakthrough or genotypic resistance) while awaiting transplant. RESULTS: One hundred twenty-two eligible patients received antiviral therapy before OLT and were followed for a median of 40.5 months (range, 0.4-123.0 months) after initiation of antiviral therapy. Forty-four (36.1%) patients developed antiviral failure; all had lamivudine monotherapy as initial treatment. Forty-two patients started salvage therapy a median of 5 months after lamivudine failure; the median Model for End-Stage Liver Disease (MELD) score was 12. Twenty-one (50%) patients had a full response to salvage therapy. Eleven (26.2%) patients had a suboptimal virologic response but remained clinically compensated. Antiviral failure was not a significant predictor of transplant or death (P = .09) or death without transplant (P = .39). Multivariate predictors of transplant or death were high MELD score, hepatocellular carcinoma, and low albumin. High MELD score and low albumin were predictors of death without transplant. CONCLUSIONS: Antiviral failure in patients with HBV on the OLT waiting list did not impair clinical outcome if recognized early and if salvage therapy is promptly initiated.

Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry.

BACKGROUND: It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies. METHODS: The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using chi(2) tests. RESULTS: Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma (P=0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis (P<0.001) and hepatitis C (P<0.001). CONCLUSIONS: Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.

Fulminant liver failure due to usnic acid for weight loss.

The use of complementary and alternative medicine (CAM) in developed countries has increased significantly over the years. Among the most popular are the weight loss supplements or "fat burners." Liver failure due to these popular remedies has been widely recognized. Usnic acid has been an ingredient of dietary supplements that cause liver failure. Its hepatotoxicity has not been recognized because it is usually mixed with other ingredients that are presumably hepatotoxic. We describe a case of a 28-yr-old woman who presented with fulminant liver failure requiring orthotopic liver transplantation, after taking pure usnic acid for weight loss. This is the first report on fulminant liver failure associated with the ingestion of pure usnic acid. A discussion about hepatotoxicity of the different compounds of dietary supplements is presented. This is a reminder for the clinicians about the potential side effects of CAM.

Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.

BACKGROUND: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition. OBJECTIVE: To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure. DESIGN: Prospective cohort study. SETTING: 17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group. PATIENTS: 308 consecutive patients with acute liver failure, admitted over a 41-month period. MEASUREMENTS: Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission. RESULTS: 73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not. CONCLUSIONS: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.

New era of liver transplantation for hepatitis B: a 17-year single-center experience.

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.