Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.

Garcinia cambogia, Either Alone or in Combination With Green Tea, Causes Moderate to Severe Liver Injury.

BACKGROUND & AIMS: Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial. METHODS: Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS. RESULTS: Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6). CONCLUSIONS: The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury. CLINICAL TRIALS: gov number: NCT00345930.

HLA-B*35:01 and Green Tea-Induced Liver Injury.

BACKGROUND AND AIMS: Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury. APPROACH AND RESULTS: Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5). CONCLUSIONS: Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.

Duodenal Microbiome and Serum Metabolites Predict Hepatocellular Carcinoma in a Multicenter Cohort of Patients with Cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is rapidly increasing in the U.S. and is a leading cause of mortality for patients with cirrhosis. Discovering novel biomarkers for risk stratification of HCC is paramount. We examined biomarkers of the gut-liver axis in a prospective multicenter cohort. METHODS: Patients with cirrhosis without a history of HCC were recruited between May 2015 and March 2020 and prospectively followed at 3 tertiary care hospitals in Los Angeles. Microbiome analysis was performed on duodenal biopsies and metabolomic analysis was performed on serum samples, collected at the time of enrollment. Optimal microbiome-based survival analysis and Cox proportional hazards regression analysis were used to determine microbiota and metabolite associations with HCC development, respectively. RESULTS: A total of 227 participants with liver cirrhosis contributed a total of 459.58 person-years of follow-up, with 14 incident HCC diagnoses. Male sex (HR = 7.06, 95% CI = 1.02-54.86) and baseline hepatic encephalopathy (HE, HR = 4.65, 95% CI = 1.60-13.52) were associated with developing HCC over follow-up. Adjusting for age, sex, baseline HE, and alkaline phosphatase, an increased risk of HCC were observed for participants with the highest versus lowest three quartiles for duodenal Alloprevotella (HR = 3.22, 95% CI = 1.06-9.73) and serum taurocholic acid (HR = 6.87, 95% CI = 2.32-20.27), methionine (HR = 9.97, 95% CI = 3.02-32.94), and methioninesulfoxide (HR = 5.60, 95% CI = 1.84-17.10). Being in the highest quartile for Alloprevotella or methionine had a sensitivity and specificity for developing HCC of 85.71% and 60.56%, respectively, with an odds ratio of 10.92 (95% CI = 2.23-53.48). CONCLUSION: Alloprevotella and methionine, methioninesulfoxide, and taurocholic acid predicted future HCC development in a high-risk population of participants with liver cirrhosis.

Long-term outcomes with oral therapy in liver transplant recipients with hepatitis B.

BACKGROUND: The long-term impact of oral hepatitis B antiviral therapy in liver transplant (LT) recipients is currently underexplored. The objective of this study was to evaluate how oral antiviral agents impact long-term renal function in this population. METHODS: We studied 79 patients who received a LT for hepatitis B and were placed on all-oral antiviral therapy after withdrawing from hepatitis B immune globulin therapy at the University of California, Los Angeles. Laboratory data were obtained through a retrospective chart review. Univariate analysis and two-sided t tests were performed. RESULTS: The mean (±SD [standard deviation]) age at the time of LT was 65.4 (± 8.2) years. The overall mean (±SD) follow-up from LT was 6.5 (±3.3) years. 22.8% (18/79) of recipients on all-oral therapy had worsening of their chronic kidney disease stage, and 17.7% (14/79) had an increase in creatinine of at least 0.3 mg/dL. There were no significant changes in creatinine and GFR in patients while on tenofovir alafenamide. Patient survival was decreased for recipients who developed detectable HBsAg. CONCLUSION: Tenofovir alafenamide appears to have less of an impact on renal function in LT recipients than other antiviral agents. HBV recurrence after transplant is associated with decreased patient survival and remains an important issue to address for LT recipients on oral antiviral therapy.

Hyperlipidemia and Nonalcoholic Steatohepatitis Predispose to Hepatocellular Carcinoma Development Without Cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease. GOAL: The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC. STUDY: From 2005 to 2015, hepatobiliary cancer patients seen in our liver cancer and liver transplant clinics were evaluated. Patients were included if above18 years old and had histologically confirmed HCC from liver biopsy, resection specimen, or explanted livers. Patients with CHB, non-HCC tumors, or missing paired tumor and nontumor liver histology were excluded. Demographic information, pertinent laboratory values, and comorbid conditions were recorded. Potential predictors were evaluated using both backward stepwise logistic regression model and classification tree model. RESULTS: Of the 1927 patients screened, 545 HCC patients (411 transplanted, 43 resected, 74 transarterial chemoembolization/radiofrequency ablation, 17 untreated) included, 29 (5.3%) patients had no cirrhosis histologically. Eleven patients had HCV, 3 had alcoholic liver disease, 3 had nonalcoholic fatty liver, and 12 had cryptogenic liver disease. Logistic regression models show that patients with hyperlipidemia and elevated serum alanine aminotransferase are more likely to develop HCC without cirrhosis (odds ratio, 1.73 and 0.40; P<0.05). CONCLUSIONS: This large cohort, histology-confirmed case-controlled study shows that patients with nonalcoholic fatty liver disease and hyperlipidemia with elevated serum alanine aminotransferase (most likely nonalcoholic steatohepatitis) are significantly associated with the development of HCC in the absence of cirrhosis.

Coil-Assisted Retrograde Transvenous Obliteration (CARTO): An Alternative Treatment Option for Refractory Hepatic Encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (OHE) is a serious complication of liver dysfunction, which is associated with severe morbidity/mortality and healthcare resource utilization. OHE can be medically refractory due to spontaneous portosystemic shunts (SPSSs) and therefore a new treatment option for these SPSSs is critical. METHODS: This is a retrospective study of 43 patients with medically refractory OHE, who underwent CARTO (Coil-Assisted Retrograde Transvenous Obliteration) procedures between June 2012 and October 2016. The patient demographic characteristics, technical and clinical outcomes with an emphasis on HE improvement, and complications are reviewed and analyzed. RESULTS: The overall clinical success rate was 91% with a significant HE improvement. Eighty-one percent of patients had clinically significant improvement from OHE and 67% of patients had complete resolution of their HE symptoms during our follow-up period of 893 ± 585 days (range 36-1881 days, median 755.0 days). The median WH score improved from 3 (range 2-4) pre-CARTO to 1 (range 0-4) post-CARTO (p < 0.001). The median ammonia level significantly decreased from 134.5 pre-CARTO to 70.0 post-CARTO (p < 0.001) in 3 days. The overall mean survival was 1465.5 days (95% CI of 1243.0 and 1688.0 days). Only three patients had recurrent HE symptoms. There were 39.6% minor complication rate including new or worsened ascites and esophageal varices, and only 2.3% major complication rate requiring additional treatment (one patient with bleeding esophageal varices requiring treatment). No procedure-related death is noted. CONCLUSIONS: CARTO appears to be a safe and effective treatment option for refractory overt hepatic encephalopathy (OHE) due to spontaneous portosystemic shunts. CARTO could be an excellent addition to currently available treatment options for these patients.

Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: The Microbiome, Microbial Markers and Liver Disease Study.

AIM: Cirrhosis is a leading cause of death worldwide, yet there are no well-established risk stratifying tools for lethal complications, including hepatocellular carcinoma (HCC). Patients with liver cirrhosis undergo routine endoscopic surveillance, providing ready access to duodenal aspirate samples that could be a source for identifying novel biomarkers. The aim of this study was to characterize the microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis to assess the feasibility of developing biomarkers for HCC risk stratification. METHODS: Thirty patients with liver cirrhosis were enrolled in the Microbiome, Microbial Markers, and Liver Disease study between May 2015 and March 2017. Detailed clinical and epidemiological data were collected at baseline and at 6-monthly follow-up visits. Duodenal aspirate fluid was collected at baseline for microbial characterization using 16S ribosomal RNA sequencing and bile acid quantification using mass spectroscopy. RESULTS: Alcohol-related cirrhosis was associated with reductions in the Bacteroidetes phylum, particularly Prevotella (13-fold reduction), and expansion of Staphylococcus (13-fold increase), compared to hepatitis C virus-related cirrhosis. Participants with hepatic encephalopathy (HE) had less microbial diversity compared to patients without HE (P < 0.05), and were characterized by expansion of Mycobacterium (45-fold increase) and Gram-positive cocci including Granulicatella (3.1-fold increase), unclassified Planococcaceae (3.3-fold increase), and unclassified Streptococcaceae (4.5-fold increase). Non-Hispanic White patients had reduced microbial richness (P < 0.01) and diversity (P < 0.05), and increased levels of conjugated ursodeoxycholic acid (glycoursodeoxycholic acid and tauroursodeoxycholic acid, P < 0.05) compared to Hispanic patients. CONCLUSION: Microbial profiles of duodenal aspirates differed by cirrhosis etiology, HE, and Hispanic ethnicity.

Eight-Week Hepatitis C Treatment with New Direct Acting Antivirals Has a Better Safety Profile While Being Effective in the Treatment-Naïve Geriatric Population Without Liver Cirrhosis and Hepatitis C Virus-RNA < 6 Million IU/mL.

AIM: Results of recent studies have confirmed the efficacy of an 8-week course of ledipasvir/sofosbuvir (LDV/SOF) in patients who are non-cirrhotics, native to treatment, are infected with hepatitis C (HCV) genotype 1, and have HCV viral load < 6 million IU/mL. However, there are limited data on a shortened treatment course in patients who are over the age of 65. METHODS: A retrospective study was performed to examine the safety, tolerability, and sustained viral response rates (SVR) of the 8-week LDV/SOF therapy compared to the 12-week LDV/SOF therapy among non-cirrhotic, treatment-naïve, genotype 1 HCV patients with viral load < 6 million IU/mL who are 65 years of age or older. RESULTS: A total of 454 patients were identified of which 182 non-cirrhotic, genotype 1 HCV-RNA < 6 million IU/mL patients received the 8-week LDV/SOF treatment and 272 received the 12-week LDV/SOF treatment. Mean [± standard deviation (SD)] aspartate aminotransferase to platelet ratio index score for the entire cohort was 0.45 ± 0.03. The mean (± SD) age for the 8-week treatment was 69.7 (± 7) years, 54.7% male and 45.3% female. The mean (± SD) age of the 12-week treatment was 71.7 (± 3) years, 56.4% male and 43.6% female. Overall, SVR-12 for the 8-week regimen was 93% and SVR-12 for the 12-week regimen was 95%. For the 182 treated with the 8-week LDV/SOF treatment, there were no serious adverse events requiring hospitalization or signs of liver failure requiring transplantation. Overall, the 8-week treatment patient cohort experienced less fatigue, headache, dry mouth, and diarrhea. This finding was statistically significant with a P value < 0.001. CONCLUSION: Eight-week LDV/SOF therapy in treatment-naive, non-cirrhotic, genotype 1 HCV patients with RNA < 6 million IU/mL was found safe, better tolerated, effective, and required less upfront cost when compared with the 12-week LDV/SOF treatment regimen in properly selected geriatric population.

Longterm follow-up of small pancreatic cystic lesions in liver transplant recipients.

Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative imaging in patients undergoing orthotopic liver transplantation (OLT). Although these are considered benign or of low malignant potential, the influence of immunosuppression after OLT may be of concern. The aim of this study was to observe the longterm outcome of these small PCLs in post-OLT patients. An institutional OLT database of 1778 consecutive OLT patients from January 2000 to December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology, fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients with 182 PCLs, of benign or low malignant potential, were identified with a mean follow-up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7 branch duct-type intraductal papillary mucinous neoplasms (B-IPMNs), 1 serous cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final diagnosis at the end of the follow-up revealed 16 B-IPMNs, 3 SCAs, and a mixed acinar-neuroendocrine carcinoma, in which the latter developed 9 years after initial diagnosis of B-IPMN. During the follow-up time, average increase in size and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The majority of incidental PCLs in OLT patients showed an indolent behavior despite immunosuppression. Risk of malignancy development was very low and comparable with normal population. Liver Transplantation 23 324-329 2017 AASLD.

Use of Sofosbuvir-Based Treatment of Chronic Hepatitis C in Liver Transplant Recipients on Hemodialysis.

BACKGROUND: The use of direct acting agents has changed the management paradigm of hepatitis C (HCV) in liver transplant (LT) recipients. However, the appropriate antiviral regimen in LT recipients on hemodialysis (HD) remains unclear. METHODS: We retrospectively evaluated the safety and efficacy of sofosbuvir-based LT recipients on HD followed at the University of California Los Angeles. RESULTS: Twelve LT recipients on HD were treated for recurrent HCV with sofosbuvir-based therapy. Indications for antiviral therapy included fibrosing cholestatic hepatitis, symptomatic cryoglobulinemia, and recurrent HCV. The causes of renal failure included hepatorenal syndrome, acute tubular necrosis and cryoglobulinemia. Of those who were not on dialysis at the time of transplantation, the mean creatinine (±SD) was 1.7 (±0.8) mg/dL. The mean age (±SD) of the cohort was 62.2 (±6.0) years. Most recipients were male (67%) and infected with genotype 1 (83%). Baseline alanine aminotransferase, total bilirubin, hemoglobin and HCV RNA values (±SD) were 53.2 (±59.4) IU/L, 3.2 (±5.5) mg/dL, 10.5 (±1.8) g/dL, and 30,499,500 (±29,655,754) IU/mL. HCV RNA levels were undetectable in all recipients at the end of therapy. The trough mean (±SD) hemoglobin of patients on treatment and on HD was 8.4 (±2.3). The sustained viral response was 58% (7/12), and the overall patient survival was 42%. All the deaths occurred a mean (±SD) after 5.4 (±3.6) months after treatment was completed. CONCLUSIONS: All patients achieved viral suppression from therapy, and over half the recipients achieved a sustained virological response. A high mortality underscores the necessity of starting antiviral treatment sooner in LT recipients and the need for larger cohort studies.

Inpatient Cost Assessment of Transjugular Intrahepatic Portosystemic Shunt in the USA from 2001 to 2012.

BACKGROUND: Despite widespread use of transjugular intrahepatic portosystemic shunt (TIPS) for treatment of portal hypertension, a paucity of nationwide data exists on predictors of the economic impact related to TIPS. AIMS: Using the National Inpatient Sample (NIS) database from 2001 to 2012, we aimed to evaluate factors contributing to hospital cost of patients admitted to US hospitals for TIPS. METHODS: Using the NIS, we identified a discharge-weighted national estimate of 61,004 TIPS procedures from 2001 to 2012. Through independent sample analysis, we determined profile factors related to increases in hospital costs. RESULTS: Of all TIPS cases, the mean charge adjusted for inflation to the year 2012 is $125,044 ± $160,115. The mean hospital cost adjusted for inflation is $44,901 ± $54,565. Comparing pre- and post-2005, mean charges and cost have increased considerably ($98,154 vs. $142,652, p < 0.001 and $41,656 vs. $46,453, p < 0.001, respectively). Patients transferred from a different hospital, weekend admissions, Asian/Pacific Islander patients, and hospitals in the Northeastern and Western region had higher cost. Number of diagnoses and number of procedures show positive correlations with hospital cost, with number of procedures exhibiting stronger relationships (Pearson 0.613). Comorbidity measures with highest increases in cost were pulmonary circulation disorders ($32,157 increase, p < 0.001). CONCLUSION: The cost of the TIPS procedure is gradually rising for hospitals. Alongside recent healthcare reform through the Affordable Care Act, measures to reduce the economic burden of TIPS are of increasing importance. Data from this study are intended to aid physicians and hospitals in identifying improvements that could reduce hospital costs.

A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

Sofosbuvir and simeprevir is effective for recurrent hepatitis C in liver transplant recipients.

BACKGROUND & AIMS: Hepatitis C is the most common indication for liver transplantation (LT). Recurrent infection is universal and can lead to progressive liver disease. Widespread use of interferon-based therapy has been limited by intolerability and adverse effects. METHODS: We retrospectively evaluated the safety, tolerability, and efficacy of sofosbuvir and simeprevir in the treatment of recurrent hepatitis C in adult (age >18) LT recipients. RESULTS: Seventy-six percent of the recipients were male and the mean age [±standard deviation (SD)] was 61 (±6.0) years. The mean time (±SD) from LT to treatment initiation was 71.8 (±77.1) months. Of the 26 patients with viral levels measured 4 weeks after starting antiviral therapy, 58% were undetectable. At the end of therapy, viral load was undetectable in all transplant recipients. The 12 week sustained viral response (SVR) was 93%. All recipients were able to complete therapy and no patients required growth factors of blood product transfusion during treatment. No patient required drug interruption of their immunosuppressant therapy. CONCLUSION: The use of sofosbuvir and simeprevir is efficacious, safe, and tolerable and should be considered in LT recipients with recurrent HCV who are candidates for antiviral therapy.

Boceprevir in liver transplant recipients.

BACKGROUND: There has been increasing interest in using protease inhibitors with pegylated interferon and ribavirin to treat recurrent hepatitis C (HCV) disease in liver transplant recipients. METHODS: We retrospectively evaluated the safety and efficacy in liver transplant recipients treated for recurrent hepatitis C genotype 1 with the combination of peginterferon, ribavirin and boceprevir. RESULTS: Twenty liver transplant recipients were treated for recurrent hepatitis C. Baseline alanine aminotransferase, total bilirubin and HCV RNA values (± SD) were 67.5 (±50.9) mg/dl, 1.78 (±1.99) U/L, and 16 955 510 (±21 620 675) IU/ml. Anaemia was a common adverse event requiring epoetin in 16 of 20 recipients and ribavirin dose reductions in 17 of 20 recipients. One-third of recipients required a blood transfusion. Filgrastim was used in 11 of 20 patients (55%) and eltrombopag in two of 20 recipients (10%) over the course of treatment. Serum creatinine level increased significantly from a baseline value of 1.33 mg/dl to 1.59 mg/dl at week 20 of boceprevir (P < 0.005). The overall sustained viral response (SVR) was 50%. Of the 14 patients who had a viral load less than 1000 IU/ml at week 4 of boceprevir, the SVR was 71%. The SVR was 83% of the 11 patients who had undetectable viral levels at week 4 of boceprevir. CONCLUSIONS: Antiviral therapy utilizing boceprevir in liver transplant recipients requires close monitoring. Anaemia and neutropenia were common requiring growth factors in most recipients. On-treatment viral responses appear promising but long-term data are needed.

Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis.

BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients. METHODS: We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin. RESULTS: Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors. CONCLUSION: Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients.

Intraductal Cooling via a Nasobiliary Tube During Radiofrequency Ablation of Central Liver Tumors Reduces Biliary Injuries.

OBJECTIVE: The objective of our study was to determine the safety and efficacy of intraductal perfusion of chilled 5% dextrose in water (D5W) via an endoscopic nasobiliary tube (NBT) for the prevention of thermal bile duct injury in patients undergoing percutaneous radiofrequency ablation (RFA) of central liver tumors. MATERIALS AND METHODS: We performed a retrospective study comparing outcomes of 32 consecutive patients who underwent percutaneous RFA of central liver tumors without intraductal perfusion of chilled D5W (control cohort) and 14 consecutive patients who underwent temporary intraductal perfusion of chilled D5W at 2 mL/s via endoscopic NBT placement before RFA (endoscopic NBT cohort). The primary and secondary outcomes were the rate of biliary complications and local tumor progression, respectively. RESULTS: All patients tolerated the procedures well. There was a significantly lower rate of biliary complications in the endoscopic NBT cohort (0/14 patients, 0%) than in the control cohort (10/32 patients, 31%) (p < 0.03) with a trend toward improved preservation of liver function in the endoscopic NBT cohort (12/14 patients, 86%) compared with the control cohort (20/32 patients, 62%) (p = 0.05). There was no difference in the rate of local tumor progression between the endoscopic NBT cohort (4/19 tumors, 21%) and the control cohort (9/39 tumors, 23%) (p = 1.0). CONCLUSION: Perfusion of chilled water through an endoscopic NBT helps prevent thermal biliary injury during RFA of central liver tumors without increasing rates of local tumor progression.

Liver transplantation in highest acuity recipients: identifying factors to avoid futility.

OBJECTIVE: To identify medical predictors of futility in recipients with laboratory Model of End-Stage Liver Disease (MELD) scores of 40 or more at the time of orthotopic liver transplantation (OLT). BACKGROUND: Although the survival benefit for transplant patients with the highest MELD scores is indisputable, the medical and economic effort to bring these highest acuity recipients through OLT presents a major challenge for every transplant center. METHODS: This study was undertaken to analyze outcomes in patients with MELD scores of 40 or more undergoing OLT during the period February 2002 to December 2010. The analysis was focused on futile outcome (3-month or in-hospital mortality) and long-term posttransplant outcome. Independent predictors of futility and failure-free survival were identified and a futility risk model was created. RESULTS: During the study period, 1522 adult cadaveric OLTs were performed, and 169 patients (13%) had a MELD score of 40 or more. The overall 1, 3, 5, and 8-year patient survivals were 72%, 64%, 60%, and 56%. Futile outcome occurred in 37 patients (22%). MELD score, pretransplant septic shock, cardiac risk, and comorbidities were independent predictors of futile outcome. Using all 4 factors, the futility risk model had a good discriminatory ability (c-statistic 0.75). Recipient age per year, life-threatening postoperative complications, hepatitis C, and metabolic syndrome were independent predictors for long-term survival in nonfutile patients (Harrels c-statistic 0.72). CONCLUSIONS: Short- and long-term outcomes of recipients with MELD scores of 40 or more are primarily determined by disease-specific factors. Cardiac risk, pretransplant septic shock, and comorbidities are the most important predictors and can be used for risk stratification in these highest acuity recipients.

The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center.

OBJECTIVE: To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure. BACKGROUND: The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity. METHODS: Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified. RESULTS: Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival. CONCLUSIONS: We present the world's largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the "sickest first" allocation approach.

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.