David C. Wolf

Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response.

Loco‐regional therapies for cirrhotic patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent tumor progression. However, there is limited data regarding the efficacy of stereotactic body radiation therapy (SBRT) as loco‐regional treatment.

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria

BACKGROUND The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution. OBJECTIVE The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis. METHODS During 1997-2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child-Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT). RESULTS The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis. CONCLUSIONS Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.

Liver transplantation for hepatocellular carcinoma: defining the impact of using extended criteria liver allografts.

Background. This series compares outcomes of patients with hepatocellular carcinoma (HCC) listed for orthotopic liver transplantation (OLT) within and outside Milan criteria, and determines the impact of extended criteria liver allografts (ECD). Methods. Records of patients listed for liver transplantation at a single center from 1998 to 2007 were reviewed retrospectively. Results. Ninety-seven HCC patients were listed for OLT, 77 underwent transplantation; 47 received ECDs and 30 standard organs. ECDs were more frequently allocated to outside Milan recipients. Wait time for OLT was shorter for outside Milan patients (4 vs. 7 months P=0.04) but hazard rate of dropout was higher (26%, 46%, and 73% at 6,12, and 24 months compared with 2%, 14%, and 60% P<0.01). Tumor size more than 3 cm (P=0.02) and model for end-stage liver disease score at listing more than 11 (P=0.04) were independent predictors of dropout. Hazard rate of OLT was similar within and outside Milan (61%, 80%, and 90% at 6, 12, and 24 months vs. 60%, 70%, and 86% P=0.38). Post-OLT survival at 1 year and 4 years were 88% and 63% within Milan compared with 79% and 62% among Milan out recipients (P=0.95). No significant post-OLT survival predictor was found. Conclusion. The use of ECD organs provided patients with HCCs outside Milan criteria access to liver transplant at a rate comparable to patients within Milan and model for end-stage liver disease HCC priority. Similar patient survival post-OLT can be achieved using standard or ECD organs. The higher risk of drop out in patients outside Milan, and even within Milan, with tumors more than 3 cm justifies the use of ECD organs for timely transplantation.

Potentiation of Acetaminophen Hepatotoxicity by Phenytoin, Leading to Liver Transplantation

We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the “nontoxic” range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.

Impact of Cardiovascular Risk Factors on Long-Term Mortality After Liver Transplantation.

Immunosuppression with calcineurin inhibitors has contributed to an increased prevalence of hypertension, diabetes, and hypercholesterolemia in patients receiving liver transplantation. This study evaluated the prevalence of cardiovascular risk factors, their management, and long-term mortality after liver transplantation. Medical records were reviewed in 333 adult patients who underwent orthotopic liver transplantation. Data were collected on medical diagnoses before and after transplantation, medication use, and on long-term mortality. The 333 patients in the study included 223 men and 110 women, mean age 59 ± 10 years. The mean follow-up was 50 ± 28 months. After transplantation, there was a high prevalence of hypertension (67%), hypercholesterolemia (46%), diabetes mellitus (42%), and chronic kidney disease (45%). Out of 333 patients in the study, 96 patients (29%) died during follow-up. Stepwise logistic regression was performed to identify the risk factors that might influence long-term mortality outcomes. Based on pretransplant characteristics, positive independent risk factors that increased mortality were age at transplant and hepatitis C. After transplantation, positive predictive factors were diabetes mellitus and cancer. A negative predictive risk factor for mortality was hypercholesterolemia. Analysis of medication after transplantation showed that positive predictive factors were the use of insulin, steroids, and antibiotics. Negative predictors for mortality were tacrolimus and mycophenolate. Our data suggest that diabetes mellitus and hepatitis C play an important role in worsening posttransplant mortality.

Original ContributionsOutcome of hepatitis C patients with and without hepatocellular carcinoma undergoing liver transplant

Objective: Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant. Methods: We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19–70 yr) in the HCC group. Results: There was no significant difference between the HCC and nonHCC groups regarding Child’s class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC. Conclusion: Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.

Timing of Hepatic Artery Reperfusion and Biliary Strictures in Liver Transplantation

During orthotopic liver transplantation (OLT), biliary tract perfusion occurs with hepatic artery reperfusion (HARP), commonly performed after the portal vein reperfusion (PVRP). We examined whether the average time interval between PVRP and HARP impacted on postoperative biliary strictures occurrence. Patients undergoing OLT from 2007 to 2009 were included if they were ≥18 years old, had survived 3 months postoperatively, and had data for PVRP and HARP. Patients receiving allografts from DCD donors were excluded. Patients were followed for 6 months post-OLT. Seventy-five patients met the study inclusion criteria. Of these, 10 patients had a biliary stricture. There was no statistical difference between those with and without biliary stricture in age, gender, etiology, MELD score, graft survival, and time interval between PVRP and HARP. Ninety percent of patients with biliary stricture had a PVRP-HARP time interval >30 minutes, as opposed to 77% of patients without biliary stricture. However, this was not statistically significant. The cold ischemia time was significantly different between the two groups. Time interval for HARP after PVRP did not appear to affect the development of biliary strictures. However, 30 minutes may be suggested as a critical time after which there is an increase in biliary stricture occurrence.

The management of eosinophilic gastroenteritis

Abstract Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal tract. No medication at present is approved by the Food and drug administration of United States for the treatment of EG. The rarity of the disease limits our experience with the different management options. It also limits the ability to conduct randomized controlled trials that could clearly delineate the efficacy of new therapeutic agents. This review assesses the various management options that have been tried on patients with EG.

Emergent stent occlusion for TIPS-induced liver failure.

Placement of a transjugular intrahepatic portosystemic shunt (TIPS) has been a well-accepted strategy in the management of cirrhosis-associated variceal bleeding and ascites since the early 1990s. Hepatic encephalopathy is a frequently reported consequence of portosystemic shunting, occurring in 20–25% of TIPS patients (1). TIPSinduced liver failure is infrequently reported. When it is seen, patient death is often the outcome. In the series of Rouillard et al., 19 of 354 patients developed severe hyperbilirubinemia within 1 month of TIPS creation (defined as a rise in the bilirubin from <85.5 to >171.0 μmol/L, i.e. from <5 to >10 mg/dl) (2). Ninety-five percent of these patients either died or required liver transplantation within 90 days of TIPS creation, in contrast to 17% of a control group of 213 patients who had undergone TIPS (P = 0.001). Angiographic techniques to reduce TIPS flow have been described in patients suffering from both TIPS-induced hepatic encephalopathy (3–5) and TIPS-induced liver failure (3, 6, 7). At our center, therapeutic shunt occlusion was performed in seven cases on account of the development of acute liver failure in the early post-TIPS period. Shunt occlusion reversed liver failure and saved the lives of three of these patients.

Ritalin improves chronic fatigue symptoms in patients with cirrhosis

Purpose: Ritalin|[reg]| (methylphenidate hydrochloride) is a central nervous system stimulant that is used to treat attention deficit hyperactivity disorder. We used a self-administered questionnaire to assess 15 patients with chronic liver disease and moderate-to-severe symptoms of chronic fatigue who received long-term treatment with Ritalin.