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Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease −4.8% vs. −2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes., Berberine ursodeoxycholate has been studied for its serum lipid and lipoprotein lowering effects. Here the authors report an 18-week phase 2, randomised, double-blind, placebo-controlled clinical trial that tested the effect of berberine ursodeoxycholate in patients with fatty liver disease and diabetes, and showed that the group taking the higher dose of the drug had reduced liver fat content.

Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401 ). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1:1:1:1 to receive placebo (n = 21) or efruxifermin 28 mg (n = 19), efruxifermin 50 mg (n = 20) or efruxifermin 70 mg (n = 20) via weekly subcutaneous injection for 16 weeks. The primary endpoint—absolute change from baseline in HFF measured as magnetic resonance imaging–proton density fat fraction at week 12—was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were −12.3% (−infinity (−inf), −10.3), −13.4% (−inf, −11.4) and −14.1% (−inf, −12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (−inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P

Background & Aims Aldafermin, an engineered analog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with nonalcoholic steatohepatitis (NASH). Methods We performed a double-blind study of 78 patients with NASH at 9 centers in the United States. Key inclusion criteria were biopsy-proven NASH with Nonalcoholic Fatty Liver Disease Activity Score ≥4, stage 2 or 3 fibrosis by NASH Clinical Research Network classification, and absolute liver fat content ≥8%, measured by magnetic resonance imaging-proton density fat fraction. Patients were randomly assigned (1:2) to groups given subcutaneous placebo (n = 25) or aldafermin 1 mg (n = 53) daily for 24 weeks. The primary outcome was change in absolute liver fat content from baseline at week 24. Secondary outcomes included serum markers and histologic measures of fibrosis improvement and NASH resolution. Results At week 24, the aldafermin group had a significant reduction in absolute liver fat content (reduction of 7.7%) compared with placebo (reduction of 2.7%; difference, reduction of 5.0%; 95% confidence interval, reduction of 8.0%−1.9%; P = .002). Aldafermin produced significantly greater decreases in levels of 7α-hydroxy-4-cholesten-3-one, bile acids, alanine and aspartate aminotransferases, and neoepitope-specific N-terminal pro-peptide of type III collagen (Pro-C3) than placebo. Fibrosis improvement (≥1 stage) with no worsening of NASH was achieved in 38% of patients receiving aldafermin vs 18% of patients receiving placebo (P = .10). NASH resolution with no worsening of fibrosis was observed in 24% of patients given aldafermin vs 9% of patients given placebo (P = .20). Discontinuations due to adverse events occurred in no patients in the aldafermin group and 4% of patients in the placebo group. Conclusions In a phase 2 trial of patients with NASH, aldafermin reduced liver fat and produced a trend toward fibrosis improvement. ClinicalTrials.gov, Number: NCT02443116.

Hepatic encephalopathy (HE), a common neurologic complication in cirrhosis, is associated with substantial disease and economic burden. Rifaximin is a non-systemic antibiotic that reduces the risk of overt HE recurrence and overt HE-related hospitalizations. Our objective was to provide an overview of the direct HE-related costs and cost benefits of rifaximin, lactulose, and rifaximin plus lactulose. A systematic review of PubMed and relevant meeting abstracts was conducted to identify publications since 1 January 2007 reporting economic data related to HE and rifaximin and/or lactulose. Further, a public database and published literature were used to estimate current costs of hospitalization for overt HE, and potential cost savings of HE-related hospitalizations with rifaximin. The methodological quality of included studies was evaluated using the Drummond checklist. A total of 16 reports were identified for inclusion in the systematic review. Globally, HE-related direct costs ranged from $US5370 to $US50,120 annually per patient. Rifaximin was associated with shorter hospital stays and reduced healthcare costs. Rifaximin also has the potential to reduce overt HE-related hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have a favourable pharmacoeconomic profile compared with lactulose (based on the incremental cost-effectiveness ratio). In addition to its clinical benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related hospitalizations, favourable adverse event profile), economic data are favourable for the use of rifaximin in patients with a history of overt HE.

Background & Aims Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis. Methods This double-blind, placebo-controlled study randomized 217 individuals with decompensated NASH cirrhosis 1:1:1 to emricasan (5 mg or 25 mg) or placebo. Patients were stratified by decompensation status and baseline model for end-stage liver disease-sodium (MELD-Na) score. The primary endpoint comprised all-cause mortality, a new decompensation event (new or recurrent variceal hemorrhage, new ascites requiring diuretics, new unprecipitated hepatic encephalopathy ≥grade 2, hepatorenal syndrome, spontaneous bacterial peritonitis), or an increase in MELD-Na score ≥4 points. Results There was no difference in event rates between either of the emricasan treatment groups and placebo, with hazard ratios of 1.02 (95% CI 0.59–1.77; p = 0.94) and 1.28 (95% CI 0.75–2.21; p = 0.37) for 5 mg and 25 mg of emricasan, respectively. MELD-Na score progression was the most common outcome. There was no significant effect of emricasan treatment on MELD-Na score, international normalized ratio, total serum bilirubin, albumin level or Child-Pugh score. Emricasan was generally safe and well-tolerated. Conclusions Emricasan was safe but ineffective for the treatment of decompensated NASH cirrhosis. However, this study may guide the design and conduct of future clinical trials in decompensated NASH cirrhosis. Lay summary Patients with decompensated cirrhosis related to non-alcoholic steatohepatitis are at high risk of additional decompensation events and death. Post hoc analyses in previous pilot studies suggested that emricasan might improve portal hypertension and liver function. In this larger randomized study, emricasan did not decrease the number of decompensation events or improve liver function in patients with a history of decompensated cirrhosis related to non-alcoholic steatohepatitis. ClinicalTrials.gov Identifier NCT03205345 .

BackgroundObesity has been associated with poor oncologic outcomes following pancreatoduodenectomy for pancreatic cancer. However, there is a paucity of evidence on the impact of obesity on postoperative complications, oncologic outcome and survival in patients with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT).MethodsFrom a database of over 1000 patients who underwent OLT during 1996–2008, 159 patients with a diagnosis of HCC were identified. Demographic data, body mass index (BMI), perioperative parameters, recurrence and survival were obtained. Complications were grouped according to Clavien–Dindo grading (Grades I–V).ResultsThere were increased incidences of life‐threatening complications in overweight (58%) and obese (70%) patients compared with the non‐obese patient group (41%) (P < 0.05). Furthermore, the incidence of recurrence of HCC was doubled in the presence of overweight (15%) and obesity (15%) compared with non‐obesity (7%) (P < 0.05). Time to recurrence also decreased significantly. Differences in mean ± standard deviation survival in the overweight (45 ± 3 months) and obese (41 ± 4 months) groups compared with the non‐obese group (58 ± 6 months) did not reach statistical significance.ConclusionsThese findings indicate that BMI is an important surrogate marker for obesity and portends an increased risk for complications and a poorer oncologic outcome following OLT for HCC.

The treatment of HIV has improved over the last decade due in part to the success of treatment with combination-therapy drug “cocktails,” better referred to as highly active antiretroviral therapy. The safety and efficacy of these regimens is often complicated by the presence of infectious hepatitis and occurrence of drug-induced liver injury. In most patients, these complications manifest as mild laboratory abnormalities and exist without clinical consequence. However, acute and chronic hepatic injury may lead to increased morbidity and mortality. It is essential to identify all potential causes of liver injury to correctly implement steps to alleviate the condition while maintaining optimal control of HIV viremia.

To evaluate the durability of the response to rifaximin for treatment of hepatic encephalopathy (HE).The nonsystemic antibiotic rifaximin has been approved for maintenance of HE remission, and several studies have indicated the efficacy of rifaximin for acute HE; however, the duration of therapeutic response for6 months remains unknown.Medical records of patients with cirrhosis who received rifaximin maintenance therapy for HE between January 2004 and May 2009 were reviewed. Model for end-stage liver disease (MELD) scores were obtained every 3 months during therapy.Of 203 patients with HE (Conn score ≥2), 149 received rifaximin monotherapy (400 to 1600 mg/d) and 54 received rifaximin (600 to 1200 mg/d) and lactulose (90 mL/d) dual therapy. Maintenance of HE remission for 1 year occurred in 81% and 67% of patients who received rifaximin monotherapy and rifaximin and lactulose dual therapy, respectively. Patient populations with a baseline mean MELD score ≤20 had few overt HE events, suggesting increased response to rifaximin in these patients.Rifaximin is effective for the management of HE in patients with cirrhosis, particularly in populations with MELD scores ≤20. Additional studies are needed to investigate the potential association between MELD scores and the efficacy of HE treatments.

Context—Tacrolimus is an immunosuppressant that undergoes therapeutic drug monitoring. The laboratory at our institution changed its immunoassay techniques from the fluorescence polarization immunoassay to the cloned enzyme donation immunoassay.Objective—To evaluate the relationship between the 2 assays and to determine the impact of the change on clinical decision making.Design—A retrospective study of patients admitted to the hospital during the assay transition period. Tacrolimus values for the 2 assays were collected for 4 weeks and compared.Setting—An academic health center.Patients—Liver transplant patients hospitalized from February 18, 2008, to March 18, 2008.Main Outcome Measure—The primary outcome was the agreement between the results of the 2 immunoassays. Secondary outcome was agreement of clinical decision making with established patient-specific therapeutic ranges or with a 30% difference in absolute values between the assays.Results—Seventy-nine pairs of tacrolimus concentrations were colle...

We report the case of a 46-year-old white male with confirmed Clostridium difficile infection for >4 weeks after fluoroquinolone therapy. The patient received two courses of metronidazole 500 mg three times daily (t.i.d.) during which time diarrhea resolved; however, symptoms recurred 14–15 days after treatment termination. He received a 2-week course of vancomycin 125 mg four times daily, with symptoms recurring 10 days after treatment conclusion. The patient then received a pulsed tapering schedule of vancomycin with adjunctive Saccharomyces boulardii. Diarrhea recurred 12 days after treatment completion. He received rifaximin 400 mg t.i.d. while hospitalized for diarrhea-associated complications. Symptoms resolved within 24 h. The patient received a 4-week regimen of rifaximin 400 mg orally t.i.d. after discharge. No further episodes of diarrhea were reported within 6 months after treatment termination. The present case supports the potential benefit of rifaximin for the treatment of recurrent Clostridium difficile infection.

Background Hepatic encephalopathy (HE), a common neurologic complication in cirrhosis, is associated with substantial disease and economic burden. Rifaximin is a non-systemic antibiotic that reduces the risk of overt HE recurrence and overt HE-related hospitalizations. Objective Our objective was to provide an overview of the direct HE-related costs and cost benefits of rifaximin, lactulose, and rifaximin plus lactulose. Methods A systematic review of PubMed and relevant meeting abstracts was conducted to identify publications since 1 January 2007 reporting economic data related to HE and rifaximin and/or lactulose. Further, a public database and published literature were used to estimate current costs of hospitalization for overt HE, and potential cost savings of HE-related hospitalizations with rifaximin. The methodological quality of included studies was evaluated using the Drummond checklist. Results A total of 16 reports were identified for inclusion in the systematic review. Globally, HE-related direct costs ranged from $US5370 to $US50,120 annually per patient. Rifaximin was associated with shorter hospital stays and reduced healthcare costs. Rifaximin also has the potential to reduce overt HE-related hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have a favourable pharmacoeconomic profile compared with lactulose (based on the incremental cost-effectiveness ratio). Conclusions In addition to its clinical benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related hospitalizations, favourable adverse event profile), economic data are favourable for the use of rifaximin in patients with a history of overt HE.

About 5,500 liver transplants are performed annually in the United States. The most common indication for liver failure resulting in liver transplantation is chronic hepatitis C virus (HCV). The management issues are complex, including universal HCV recurrence following transplantation, proper immunosuppression management, and morbidity and mortality issues. Treatment options with antiviral therapies have been minimally effective and are fraught with various drug-related side effects. Various outcomes exist for liver transplantation recipients with HCV recurrence. The side effects are numerous, particularly neutropenia, anemia, and depression, but are similar to the complications seen in the nontransplant community. This report discusses the current treatment options for liver transplant recipients with hepatitis C.

Previous data have suggested that the nonsystemic antibiotic rifaximin may be effective for the treatment of Clostridium difficile infection (CDI). This single-center retrospective study evaluated the efficacy of rifaximin for the treatment of CDI refractory to standard treatments in patients who had received liver transplants. Among 205 patients who had received liver transplants between July 2001 and December 2007, 3 patients with a confirmed diagnosis of C. difficile experienced recurrent diarrhea even though they received standard therapy. Patient 1, a 56-year-old male, patient 2, a 62-year-old male, and patient 3, a 73-year-old female, developed CDIs 190, 318, and 2310 days after transplantation, respectively. All patients experienced symptom recurrences after oral metronidazole therapy (250 mg 3 times daily for either 14 or 28 days) and after oral vancomycin therapy (125 mg 4 times daily for 14 days). Long-term vancomycin treatment (ie, 28 days) was required for patients 1 and 2. Vancomycin was discontinued in patient 3 because of increased creatinine levels. Oral rifaximin (400 mg 3 times daily) was initiated immediately after discontinuation of vancomycin therapy. Within 36 to 48 hours of the initiation of rifaximin treatment, diarrheal symptoms were resolved in all patients. After completing a 28-day course of rifaximin, patient 1 remained symptom-free during 185 days of follow-up, and patient 2 remained symptom-free during 250 days of follow-up. Patient 3 reported no symptoms within 155 days after the completion of rifaximin treatment. These findings suggest that rifaximin may be effective for the treatment of recurrent CDI and may provide a therapeutic option for CDI in immunocompromised patients.

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P

Therapy related chronic myelomonocytic leukemia (t-CMML) is rare. We report a 23-year-old female who developed acute fulminant hepatic failure after drug overdose. She underwent ABO incompatible orthotopic liver transplant. She received cyclophosphamide along with other immunosuppressants. Seven years later, she was diagnosed with t-CMML-2 with 45XX,-7 karyotype. She received 4 cycles of azacitidine and proceeded with allogeneic bone marrow transplant. This is the first a case of t-CMML reported in a liver transplant recipient. In this article, we also summarize all reported cases of t-CMML, and we review therapy related MDS in recipients of solid organ transplant.

Liver transplantation (LT) provides long-term survival for adults with end-stage liver disease. As a result of improved survival and an aging United States population the demand for LT in older patients is expected to increase. The aim of this study was to describe the transplantation trends in the older recipient (older than 65 years).Using the United Network for Organ Sharing database, we identified LT recipients between 1990 and 2006. We used Kaplan-Meier method to calculate overall survival (1, 3, 5 and 10 years) and Cox regression for predictors of survival.During the study period 5630 (7.6%) LT recipients were older than 65 years. There were 4256 (79.4%) whites, Hispanic (10.3%), African Americans (AA) (3.6%), and rest (6.7%). There was an increase in LT for older than 65 years from 4.1% in 1990 to 10.2% in 2006 (P=0.002) and a regional variation (P0.001). The 10-year patient and graft survival was 60% and 57% for less than 65 years versus 42% and 40% for more than 65 years (P0.0001). With age stratification (65-75 years vs.75 years), there was no difference in survival but when adjusted for race there was a significant difference in graft survival with a 10 year (white 40%, Hispanic 44%, and AA 19%) (P=0.04).The demand for LT in recipients older than 65 years is increasing. Although their survival is lower in comparison with recipients less than 65 years, there seems to be no difference in unadjusted survival with age stratification above 65 years. Among ethnic minorities, there was a disproportionately lower percentage of African Americans LT and a decreased survival.

Background Recent reports have documented ethnic disparity in access to health care. This disparity appears to exist in organ transplantation and the contributing factors include lack of insurance as well as poor socioeconomic status. The role of geographic location and ethnic composition on accessibility to liver transplantation (LT) is unclear. Therefore, the aim of this study was to determine ethnic transplantation trends based on United Network for Organ Sharing (UNOS) regions. Methods Using the UNOS database, we identified all adults (> or =18 years) that received LT between 2000 and 2005. We excluded multiorgan transplants and living donor transplantation. The data collected included ethnicity, transplantation rate, and UNOS region. Data were analyzed using the chi test. Results A total of 30,311 patients received a LT during the study period. Of these, 22,673 (74.8%) were white, 3621 (12%) were Hispanic, 2490 (8.2%) were African Americans, and the rest of other ethnic groups (5%). Liver transplantation based on ethnicity was region specific, with the lowest for African Americans in region 6 (2.7%), for Hispanics in region 11 (2.2%), and for whites in region 5 (57.6%), respectively. There was no consistent correlation between the ethnicity of the recipients and the ethnic composition of the geographic location (region). Conclusion Significant variations in access to liver transplantation for ethnic minorities exist across geographic lines. Understanding the interaction between ethnic minorities with end-stage liver disease in a geographic location and a transplant center will be invaluable as a first step in identifying the key nonmedical factors that play a role in this disparity.

Patients with chronic hepatitis C virus (HCV) infection and disease-related complications – among them cirrhosis and liver failure – pose a particular management challenge. Some of these patients may fail to respond to current therapy (non-responders), and some are affected so severely that treatment puts them at an unacceptable risk for complications. Treatment with pegylated interferon (peg-IFN) plus ribavirin improves hepatic enzyme levels and eradicates the virus in ≈50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic and patient-related factors influence response to IFN therapy; many of these factors cannot be modified to improve long-term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Retreatment options for patients who have failed therapy are limited. Retreatment with peg-IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment-resistant patients, has demonstrated efficacy in the retreatment of non-responders and relapsers. Although the optimal duration of retreatment and the benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. This article reviews the risk factors for HCV treatment resistance and discusses the assessment and management of difficult-to-treat patients.

Chronic liver disease is a major source of morbidity and mortality in the United States today. There is little information on the interethnic variation in the clinical presentation, therapeutic responses and prognosis of individuals with liver disease. This review will discuss the ethnic variations and implications of the most common liver diseases.

Introduction: Conventional therapy to prevent HBV recurrence in liver transplant (LTx) recipients consists of Hepatitis B Immune Globulin (HBIg). The aim of this review is to investigate the safety and efficacy of converting HBIg and LAM therapy to ADV and LAM therapy. Methods: A retrospective review involving all liver transplant patients with HBV maintained on HBIg and LAM therapy. Results collected included: gender, age, HBV serological and DNA status (COBAS AmpliScreen PCR-based testing). Serologic testing was done every three months. Patients were followed for drug reactions, therapy compliance, and immune suppression compliance. A cost benefit analysis was done for drug comparisons using United States currency values. Results: Patient demographics included: Male (n=6), Female (n=4), mean age 44 years (range 33 to 65). The mean length of follow up since therapy conversion (from HBIg and LMV to ADV and LMV) was 21 months (range 16 to 25 months). Serological status at time of conversion revealed that DNA status remained negative in all patients, HBsAg negative in 10/10, HB eAg (+) (5/10) and HBeAb (+)(5/10). None of the patients experienced an increase in transaminases while on dual ADV and LAM therapy. All patients were maintained on immune suppression monotherapy (tacrolimus) at 7–9 ng/mL. All patients reported compliance with the dual therapy and that they experienced no drug related side effects. Mean yearly costs for ADV and LAM was 7,235.00 United States dollars (range 6,550.00 to 8,225.00); while mean monthly costs for HBIg and LAM; 9225.00 (range 7205.00 to 12005.00). Conclusion: The above results demonstrate beneficial effects of ADV and LAM in place of the current standard of HBIg and LAM therapy. Safety and short term results show nucleoside therapy is adequate at preventing HBV viral recurrence. Lastly, the economic benefit for ADV and LAM vastly outweighed the HBIg and LAM group.

Malignancy is a well defined complication of chronic immunosuppression. Post transplant malignancies appear to be related to cumulative doses of immunosuppression, and in pediatric patients, acute infection of previously naive patients. The most commonly encountered malignancy in this age population is Post Transplant Lymphoproliferative Disorder (PTLD). PTLD is not a single entity but rather represents a continuum of disease. Treatment of PTLD should be initiated with immunosuppression reduction. Standard dose chemotherapy leads to significant morbidity. With the introduction of anti-CD20 antibody treatment with rituximab, chemotherapy has become second line therapy. The occurrence of solid malignancy appears to be associated with chronic immunosuppression. These cancers include those of skin, gynecologic organs, and the rectum, all of which appear to have the strongest association with viral mediators. Several strategies have been postulated to minimize the occurrence of malignancy. These include ganciclovir prophylaxis for the prevention of PTLD and the use of mychophenolic acid and TOR inhibitor maintenance to diminish the incidence of PTLD and solid malignancies. This leaves transplant physicians with several new and novel immunosuppressive agents with uncertain oncologic potentials that will need to be examined over the next decade.

Liver transplant teams are often faced with the challenges of managing viral recurrence after liver transplantation. Hepatitis C virus (HCV) remains the most challenging viral disease in the transplant community. Strategies to prevent and delay viral recurrence have slowly developed over the past 5 years. Hepatitis B virus (HBV), previously a contraindication for liver transplantation due to recurrence and cholestasis with allograft failure, is now one of the more favorable indications for liver transplantation as a result of current therapeutic options. This review investigates the up-to-date information on treatment outcomes for HCV and HBV in the period following liver transplant.

Introduction. Herpes simplex virus (HSV) is seen throughout the world and can be treated with acyclovir. We present a case of fulminant hepatic failure (FHF) as a result of disseminated HSV infection in a pregnant patient during the second trimester. Methods. The medical records of a patient suffering from HSV-related fulminant hepatic failure were collected. A review of the literature was collected and reported. Results. A previously healthy female presented with fulminant hepatic failure at a local emergency room complaining of a 5-day history of fever, nausea, vomiting, and right side abdominal pain that radiated to the back. She was diagnosed with fulminant hepatic failure and progressed into a coma. The patient underwent orthotopic liver transplantation (OLT) prior to the diagnosis of HSV and then treated successfully with acyclovir. Conclusion. Treatment of HSV fulminant hepatitis is dependent up on early suspicion and prompt intervention. In addition, antiviral therapy may need to be lifelong.

Treatment protocols for chronic liver disease caused by hepatitis C virus (HCV) and hepatitis B virus have different outcomes among various ethnic groups. Outcome information has been slowed by the limited number of trials aimed at the various ethnic minorities. The current opinion is that there is a vast difference in treatment success with antiviral therapies, especially with African-American men suffering from chronic HCV. This article investigates the up-to-date information in treatment outcomes for the two diseases, and liver transplant survivals.

In at-risk populations, shared routes of transmission lead to high rates of concordance between infection with human immunodeficiency virus (HIV) type 1 and hepatitis C virus (HCV). In the era of highly active antiretroviral therapy (HAART), end-stage liver disease (ESLD) has emerged as a leading cause of mortality in coinfected patients. HAART-related toxicities have been implicated, especially when given to patients with viral hepatitis. Rates of response to treatment for HCV infection in coinfected patients continue to lag behind those in monoinfected patients, even with the advent of pegylated interferons. Liver transplantation has been approached with caution in this population because of concern about the sequelae of immunosuppression and HAART-related hepatotoxicity, and results have been conflicting. Clinical and serological markers of ESLD in coinfected patients, management of cirrhosis, and the appropriateness of transplantation are discussed.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as the most common chronic liver disease worldwide. The aim of this study is to investigate the transplantation trends of liver transplant (LT) recipients with NASH. Using the United Network for Organ Sharing database, we found a steady increase in LT rate especially in those more than 65 years old. We identified differences across ethnic groups and United Network for Organ Sharing regions. This study highlights the impact of the rising prevalence of NASH on the demand for LT and provides invaluable information to healthcare policymakers and the transplant community about the target groups and geographic location for focused and early intervention.

The increases in survival of patients infected with human immunodeficiency virus is attributed to the introduction of combination human immunodeficiency virus antiviral therapy, better known as highly active anti-retroviral therapy. In fact, survival statistics have improved such that individuals often succumb to other disease entities, notably liver failure and not from acquired immunodeficiency syndrome complications. Liver transplantation has been introduction in this patient population in several centres around the world. This review will discuss the current clinical status of liver transplantation in individuals suffering from human immunodeficiency virus infection.

BACKGROUND Resistant hepatitis B virus (HBV) strains develop in 30% of liver transplant recipients treated with lamivudine within 2 years from the time of transplantation. OBJECTIVE To assess safety and outcomes of tenofovir salvage therapy for patients with lamivudine resistance in a retrospective cohort of liver-transplanted patients. METHODS Medical records were retrospectively evaluated for patients who received tenofovir. Data collected included demographics, HBV serologic information prior to and during tenofovir therapy, drug-related complications, and creatinine clearance. Criteria for lamivudine resistance included elevation of liver chemistries along with reappearance of hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA. RESULTS Sixteen patients showed resistance to lamivudine at 10–85 months (median 26) following liver transplantation. Tenofovir 300 mg/day orally was added in 8 patients 1–66 months after the development of viral lamivudine resistance and continued for 14–26 months (median 19.3). All 8 patients experienced HBV DNA viral suppression, with 7 currently nondetectable. No adverse events were reported, and creatinine clearance was not impaired. CONCLUSIONS Our results suggest that tenofovir safely and markedly decreases replication of lamivudine-resistant HBV variants after liver transplantation and is another potential option for the treatment of HBV lamivudine resistance.

BACKGROUND Sirolimus is an immunosuppressant that exerts anti-rejection activity by inhibiting T-cell activity and is used to treat chronic rejection and calcineurin-related nephrotoxicity. Unlike tacrolimus and cyclosporine, it has no effect on calcineurin activity in liver transplant recipients. OBJECTIVE To report correlates of survival outcomes in a series of patients with putative sirolimus-related hepatotoxicity after liver transplant. METHODS We retrospectively reviewed the medical records of patients who underwent a liver transplant for chronic hepatitis C virus (HCV) and who received sirolimus immunosuppressive therapy between November 2000 and November 2003. Extracted data included sirolimus serum concentrations, frequency of sirolimus-related adverse effects, drug-related clinical hepatitis, and survival outcomes. RESULTS Ten patients were found to have been treated with sirolimus for either renal insufficiency (n = 6) or chronic rejection (n = 4). Six patients had liver biopsies, while the remaining 4 patients were clinically diagnosed with rejection. Two of the 6 patients demonstrated changes consistent with sinusoidal congestion and one with eosinophilia, consistent with an allergic drug reaction. HCV viral load increased slightly, from 600 000 to 700 000 IU/mL. Mean baseline transaminase levels were 45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase, with peak levels of 210 and 180 IU/L, respectively. The time to transaminase increase was a mean of 21 days when sirolimus was added, with resolution within 27 days (mean) after its discontinuation. No changes were evident in antiviral therapy. Combination sirolimus and tacrolimus concentrations were maintained at >10 ng/mL; average monotherapy with sirolimus was 12 ng/mL, and average time on therapy was 25 weeks. CONCLUSIONS Sirolimus-related hepatotoxicity is an important complication after liver transplant. Immediate recognition is critical to avoid confusion with other causes of abnormal serum aminotransferases after liver transplant, and discontinuation of the drug may be required.