Atypical Large Vessel Vasculitis Presenting With Cholestatic Liver Abnormalities: Case-Based Review.

ABSTRACT: Clinicians usually easily recognize cranial manifestations of giant cell arteritis (GCA) such as new-onset headache, jaw claudication, scalp tenderness, and abrupt changes in visual acuity or blindness; however, when presented with an aberrant clinical course, the diagnosis becomes more elusive. In addition to temporal arteries and other extracranial branches of the carotid arteries, large vessel vasculitis (LVV) can also affect other blood vessels including coronary arteries, aorta with its major branches, intracranial blood vessels, and hepatic arteries.Over time, the scope of the symptoms typically associated with LVV has broadened and includes cases of fever of unknown origin accompanied with other constitutional symptoms that can mimic a range of neoplastic and infectious diseases. In up to half of patients with atypical LVV, liver enzyme level elevations with a cholestatic pattern have been observed. Alkaline phosphatase level and γ-glutamyl transferase level elevations tend to be more prevalent in those LVV patients with vigorous inflammatory responses, particularly in those with fever and other nonspecific constitutional symptoms. These patients also have more profound anemia and thrombocytosis. With the exception of rare instances of vasculitides and granulomas affecting the liver tissue, liver biopsy is generally of little help and primarily shows nonspecific changes of fatty liver.In this article, we review 3 patients who were eventually diagnosed with atypical LVV. The diagnosis was confirmed with temporal artery biopsy in 2 patients and with positron emission tomography/computed tomography in 1 patient. The common hepatic abnormality observed in all patients was the elevation of alkaline phosphatase level, which tended to respond rapidly to initiation of immunosuppressive treatment.

Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis.

BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

Predicting Low Risk for Sustained Alcohol Use After Early Liver Transplant for Acute Alcoholic Hepatitis: The Sustained Alcohol Use Post-Liver Transplant Score.

Early liver transplant (LT) for alcohol-associated disease (i.e., without a specific sobriety period) is controversial but increasingly used. Using the multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) cohort, we aimed to develop a predictive tool to identify patients pretransplant with low risk for sustained alcohol use posttransplant to inform selection of candidates for early LT. We included consecutive ACCELERATE-AH LT recipients between 2012 and 2017. All had clinically diagnosed severe alcoholic hepatitis (AH), no prior diagnosis of liver disease or AH, and underwent LT without a specific sobriety period. Logistic and Cox regression, classification and regression trees (CARTs), and least absolute shrinkage and selection operator (LASSO) regression were used to identify variables associated with sustained alcohol use post-LT. Among 134 LT recipients for AH with median period of alcohol abstinence pre-LT of 54 days, 74% were abstinent, 16% had slips only, and 10% had sustained alcohol use after a median 1.6 (interquartile range [IQR]: 0.7-2.8) years follow-up post-LT. Four variables were associated with sustained use of alcohol post-LT, forming the Sustained Alcohol Use Post-LT (SALT) score (range: 0-11): >10 drinks per day at initial hospitalization (+4 points), multiple prior rehabilitation attempts (+4 points), prior alcohol-related legal issues (+2 points), and prior illicit substance abuse (+1 point). The C statistic was 0.76 (95% confidence interval [CI]: 0.68-0.83). A SALT score ≥5 had a 25% positive predictive value (95% CI: 10%-47%) and a SALT score of <5 had a 95% negative predictive value (95% CI: 89%-98%) for sustained alcohol use post-LT. In internal cross-validation, the average C statistic was 0.74. Conclusion: A prognostic score, the SALT score, using four objective pretransplant variables identifies candidates with AH for early LT who are at low risk for sustained alcohol use posttransplant. This tool may assist in the selection of patients with AH for early LT or in guiding risk-based interventions post-LT.

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. METHODS: We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. RESULTS: Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01). CONCLUSIONS: In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

Idiopathic hyperammonemia after solid organ transplantation: Primarily a lung problem? A single-center experience and systematic review.

BACKGROUND: Idiopathic hyperammonemia syndrome (IHS) is an uncommon, often deadly complication of solid organ transplantation. IHS cases in solid organ transplantation seem to occur predominantly in lung transplant (LTx) recipients. However, to the best of our knowledge, the occurrence of IHS has not been systematically evaluated. We set out to identify all reported cases of IHS following nonliver solid organ transplantations. METHODS: Retrospective review of our institutional experience and systematic review of the literature. RESULTS: At our institution six cases (of 844 nonliver solid organ transplants) of IHS were identified: five occurred following LTx (incidence 3.9% [lung] vs 0.1% [nonlung], P=.004). In the systematic review, 16 studies met inclusion criteria, reporting on 32 cases of IHS. The majority of IHS cases in the literature (81%) were LTx-recipients. The average peak reported ammonia level was 1039 µmol/L occurring on average 14.7 days post-transplant. Mortality in previously reported IHS cases was 69%. A single-center experience suggested that, in addition to standard treatment for hyperammonemia, early initiation of high intensity hemodialysis to remove ammonia was associated with increased survival. In the systematic review, mortality was 40% (four of 10) with intermittent hemodialysis, 75% (nine of 12) with continuous veno-venous hemodialysis, and 100% in six subjects that did not receive renal replacement to remove ammonia. Three reports identified infection with urease producing organisms as a possible etiology of IHS. CONCLUSION: IHS is a rare but often fatal complication that primarily affects lung transplant recipients within the first 30 days.

National survey of provider opinions on controversial characteristics of liver transplant candidates.

Candidate selection for liver transplantation presents challenging ethical issues that require balancing the principles of justice and utility. The goal of this study was to assess the opinions of U.S. transplant providers regarding the ways in which controversial medical and psychosocial characteristics influence patient eligibility for liver transplantation. An online, anonymous survey about adult patient characteristics was sent to providers (hepatologists, surgeons, psychiatrists, and social workers) at all 102 active adult liver transplant centers in the United States. A majority of the providers (251/444 or 56.5%) completed the survey. The providers were queried about 8 characteristics, and the 3 that were ranked most controversial were incarceration, marijuana use, and psychiatric diagnoses. Most providers identified a patient age ≥ 80 years (62.7%), a body mass index ≥ 45 kg/m2 (56.6%), and current incarceration with a lifetime sentence (54.7%) as absolute contraindications to liver transplantation. In a multivariate analysis, the identification of absolute contraindications varied significantly with the provider type, the center volume, and the geographical region. Less than half of the providers reported that their centers had written policies regarding most of the characteristics examined. In conclusion, providers differ significantly in their opinions on controversial patient characteristics and transplant contraindications. Along with a paucity of literature data on outcomes, these provider differences may play a role in the fact that many centers do not have formal policies for selecting patients with these characteristics. Evidence-based data on the outcomes of such patients are needed to guide the formation of written policies to better standardize eligibility criteria.

Bilateral optic neuritis in acute hepatitis C.

A 34-year-old woman developed bilateral optic neuritis 2 weeks after the onset of acute hepatitis C. The strong temporal relationship between the initial clinical manifestations of hepatitis C and the development of optic neuritis provides a basis for thinking that the hepatitis caused the optic neuritis After corticosteroid treatment, the optic neuropathy markedly improved but left behind retinal nerve fiber thinning, as measured by optical coherence tomography, and optic disc pallor. Optic neuritis has been reported in conjunction with hepatitis A and B but not with hepatitis C.

Acute cellular rejection in hepatitis C recipients following liver transplantation in the era of direct-acting antivirals: chronological analysis of the United Network for Organ Sharing database.

INTRODUCTION: Interferon (IFN) treatment for liver transplant (LT) recipients with hepatitis C virus (HCV) increases acute cellular rejection (ACR) and worsens graft and patient survival. It is unknown if direct-acting antivirals (DAAs) affect rejection rates or post-transplant survival. METHOD: The United Network for Organ Sharing STAR files of December 2017 (n = 25,916) were analyzed. RESULTS: Compared with non-HCV-LT, HCV-LT survival was worse in the IFN-era (2007-2008) and IFN+DAA-era (2011), but not in the DAA-era (2014-2015). ACR6m rate has been less frequent in newer eras and was lower in HCV-LT than in non-HCV-LT in both the DAA-era (6.9% vs. 9.3%, P < 0.001) and in the IFN+DAA-era (8.8% vs. 11.8%, P = 0.001), but not in the IFN-era (10.8% vs. 11.0%, P = 0.39). HCV-LT recipients who had ACR6m had worse 2-year survival than those without ACR6m, in the IFN-era (80.0% vs. 88.4%, P < 0.0001) and in the IFN+DAA-era (81.4% vs. 89.2%, P < 0.01) but not in the DAA-era (90.4% vs. 93.2%, P = 0.085). Cox proportional hazard model identified ACR6m as independent risk factor for mortality in HCV-LT in the IFN-era (HR = 1.88, P ≤ 0.001) and in the IFN+DAA-era (HR = 1.84, P = 0.005), but not in the DAA-era (P = n.s.). CONCLUSIONS: Two-year survival of HCV-LT recipients were significantly better in the DAA-era; these were associated with reduced rate and impact of ACR6m.

Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS: The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C.

BACKGROUND: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. METHODS: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. RESULTS: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. CONCLUSIONS: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.

Locoregional Therapy With Curative Intent Versus Primary Liver Transplant for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

BACKGROUND: Locoregional therapy with curative intent (CLRT) followed by salvage liver transplantation (SLT) in case of hepatocellular carcinoma (HCC) recurrence is an alternative to primary liver transplantation (LT) in selected patients with HCC. METHODS: We performed a systematic review and meta-analysis of studies comparing the survival of patients treated with CLRT versus LT, stratified by the stage of liver disease, extent of cancer, and whether SLT was offered or not. RESULTS: We included 48 studies involving 9835 patients (5736 patients with CLRT and 4119 patients with primary LT). Five-year overall survival (OS) and disease-free survival (DFS) was worse for all categories of CLRT combined, than for primary LT (odds ratio [OR] for OS, 0.59; 95% confidence interval [CI], 0.48-0.71; P < 0.01). However, 5-year OS for CLRT and primary LT was not significantly different among patients with (i) Child-A cirrhosis and (ii) single HCC lesion, although DFS was worse. When SLT was offered after CLRT, intention-to-treat analysis showed no significant difference in 5-year OS (OR, 1.0; 95% CI, 0.6-1.7) between CLRT-SLT and primary LT, though noninferiority could not be shown. Only 32.5% patients with HCC recurrence after CLRT actually received SLT, as the rest were not medically eligible. Thus, the DFS was worse with CLRT-SLT (OR, 0.31; 95% CI, 0.2-0.6) compared with LT. CONCLUSIONS: CLRT-SLT may be offered as first-line therapy to patients with HCC and well-compensated cirrhosis instead of primary LT because it may lead to better utilization of donor liver. However, a large proportion of patients with HCC recurrence after CLRT may not be candidates for SLT.

Transjugular intrahepatic portosystemic shunt does not independently increase risk of death in high model for end stage liver disease patients.

Physicians often exclude patients with a model for end-stage liver disease (MELD) score ≥ 18 from a transjugular intrahepatic portosystemic shunt (TIPS) procedure due to the concern for higher risk of death. We aimed to determine if TIPS increased the risk of death in these patients. We analyzed the interaction between TIPS and MELD in 106 patients with TIPS and 79 with intractable ascites without TIPS. We performed Cox proportional hazard regression, including both TIPS and MELD as time-dependent covariates together with their interaction, to calculate the impact of TIPS on the risk of death associated with a high MELD score. We found a negative interaction between a high MELD score and a history of TIPS, with potentially important effect sizes. Patients with MELD scores ≥18 had a 51% lower incremental risk of death (lower risk than would be expected from the combined independent risks of MELD and needing/receiving TIPS) associated with TIPS than patients with MELD scores <18 (hazard ratio for TIPS, 0.49; 95% confidence interval, 0.10-2.45) in the first 6 months following TIPS. There was an 80% lower incremental risk of death among patients with a MELD score ≥18 (hazard ratio for TIPS, 0.20; 95% confidence interval, 0.03-1.23) 6 months after the TIPS procedure. Conclusion: Risk of death is associated with underlying disease severity as shown by the MELD score and the need for TIPS, and both history of TIPS and high MELD score independently increased the risk of mortality. However, the risk of death after TIPS was progressively lower than expected as the MELD score increased. (Hepatology Communications 2017;1:460-468).

Severe erythema multiforme responding to interferon alfa.

Erythema multiforme (EM) is a targetoid eruption with interface pathology often triggered by a hypersensitivity response to a variety of infections, most commonly herpes simplex virus. Hepatitis C virus is rarely associated with EM. We present a 37-year-old man with an 8-year history of severe EM unresponsive to valacyclovir, acitretin, and cyclosporin, and marginally responsive to high-dose prednisone. The eruption had cleared 6 years previously during treatment with interferon for his concurrent hepatitis C virus. Although his viral titer was undetectable, we initiated therapy with interferon and ribavirin. The patient responded dramatically within 2 months and remained clear of EM after 1 year of continued interferon therapy. This is the third case reported in the world literature documenting a response of EM to interferon, and the first case in which hepatitis C virus was undetectable in serum prior to interferon therapy.

Positive serum cryoglobulin is associated with worse outcome after liver transplantation for chronic hepatitis C.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection in patients after liver transplantation is an important clinical problem. Because serum cryoglobulins (CG) are known to be associated with an increased incidence of cirrhosis in nontransplant patients, the authors tested the hypothesis that CG would also predict aggressive recurrent HCV in patients after liver transplantation. METHODS: Using a longitudinal database, the outcomes of 105 allografts transplanted into 97 HCV-positive patients from 1991 through 2002 were analyzed on the basis of CG status using a retrospective cohort design. Fifty-nine CG-negative and 38 CG-positive patients were identified. Histologic outcomes and graft survival were analyzed using Kaplan-Meier estimates and Cox univariate and multivariate analyses. Both overall survival and HCV-specific survival (non-HVC-related deaths and graft losses censored) were analyzed. RESULTS: By Kaplan-Meier estimates, CG-positive patients showed earlier graft failure with decreased time to severe histologic activity and fibrosis as compared with CG-negative patients (P<0.05 for all outcomes). By univariate analysis, CG-positive patients had significantly higher risk ratios for shortened HCV-specific graft survival, severe activity-free survival, and severe fibrosis-free survival as compared with CG-negative patients (P<0.05 for all outcomes). In the multivariate model, CG was an independent predictor for severe activity-free, severe fibrosis-free, and HCV-specific graft survival (P<0.05 for all outcomes). CONCLUSIONS: CG-positivity is associated with severe recurrent HCV disease in liver transplant recipients.

Alcohol in hepatocellular cancer.

Hepatocellular cancer accounts for almost half a million cancer deaths a year, with an escalating incidence in the Western world. Alcohol has long been recognized as a major risk factor for cancer of the liver and of other organs including oropharynx, larynx, esophagus, and possibly the breast and colon. There is compelling epidemiologic data confirming the increased risk of cancer associated with alcohol consumption, which is supported by animal experiments. Cancer of the liver associated with alcohol usually occurs in the setting of cirrhosis. Alcohol may act as a cocarcinogen, and has strong synergistic effects with other carcinogens including hepatitis B and C, aflatoxin, vinyl chloride, obesity, and diabetes mellitus. Acetaldehyde, the main metabolite of alcohol, causes hepatocellular injury, and is an important factor in causing increased oxidant stress, which damages DNA. Alcohol affects nutrition and vitamin metabolism, causing abnormalities of DNA methylation. Abnormalities of DNA methylation, a key pathway of epigenetic gene control, lead to cancer. Other nutritional and metabolic effects, for example on vitamin A metabolism, also play a key role in hepatocarcinogenesis. Alcohol enhances the effects of environmental carcinogens directly and by contributing to nutritional deficiency and impairing immunological tumor surveillance. This review summarizes the epidemiologic evidence for the role of alcohol in hepatocellular cancer, and discusses the mechanisms involved in the promotion of cancer.

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.

Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States.

OBJECTIVES: Southeast Asian immigrants, with a high prevalence of both hepatitis B and latent tuberculosis, constitute a large proportion of immigrants to the United States. Isoniazid hepatotoxicity may be associated with hepatitis B. This study was conducted to document the prevalence and interaction of hepatitis B, latent tuberculosis, and isoniazid toxicity. METHODS: Hepatitis B surface antigen (HBsAg) and tuberculin skin testing was done on 743 Vietnamese immigrants to the Midwest between January, 1991 and December, 1999. HBsAg positive cases were tested for hepatitis B e antigen (HBeAg). All tuberculin skin test-positive patients were treated with isoniazid, unless contraindicated. Complications of isoniazid treatment and compliance with hepatitis B virus immunization recommendations were evaluated. RESULTS: One hundred three subjects (13.86%) had HBsAg, and 43 (5.7%) HBeAg. Prevalences of latent tuberculosis were similar in HBsAg positive (53%) and HBsAg negative (45%) subjects. Sixty-two percent of HBeAg positive versus 19% of HBeAg negative subjects had hepatotoxic side effects requiring discontinuation of treatment (relative risk [RR] = 11.38, CI = 5.49 < RR < 23.59, p < 0.001). Three cases of severe isoniazid hepatitis occurred in 21 HBeAg positive subjects, versus no cases in 121 HBeAg negative cases treated with isoniazid (RR = 7.72, CI = 5.02 < RR < 11.88, p < 0.001). Only 58% of subjects at risk of developing hepatitis B virus infection were appropriately immunized. CONCLUSIONS: Vietnamese immigrants have a high prevalence of hepatitis B and latent tuberculosis. HBeAg positive cases have a 7.7-fold increased risk of serious isoniazid toxicity and an 11.3-fold increased risk of isoniazid side effects requiring discontinuation of treatment. HBeAg represents an important risk factor for severe isoniazid hepatitis.

Lichenoid graft vs. host disease following liver transplantation.

BACKGROUND: Graft vs. host disease (GVHD) is a common complication of bone marrow transplantation (BMT) but is rarely seen after solid organ transplantation. METHODS: We report a case of lichenoid GVDH arising in a 60-year-old man 10 weeks after orthotopic liver transplantation. RESULTS: Skin biopsies revealed changes suggestive of lichenoid GVHD, but histological features differed from those described in post bone marrow (stem cell) transplant GVHD, in that a dense lymphoid infiltrate was present. The brisk infiltrate contained eosinophils that initially led to concern for a lichenoid drug eruption. The patient developed multiorgan GVHD after reduction in immunosuppression. The diagnosis of chronic GVHD was confirmed by the demonstration of chimerism in the patient's peripheral blood. The generalized cutaneous eruption and systemic manifestations responded to salvage therapy including intravenous immunoglobulin infusion, increased immunosuppression with high-dose steroids, mycophenolate mofetil, and systemic and topical tacrolimus. CONCLUSIONS: In interpreting skin biopsies, it is important to recognize that brisk inflammation may be seen in GVHD in the setting of solid organ transplantation, in contrast to the more sparse inflammation typical of GVHD following BMT. The clinical and histologic differential diagnosis included the eruption of lymphocyte recovery, drug reaction, and viral exanthem. We provide a conceptual framework for evaluating generalized cutaneous changes that may occur post transplantation.

New national liver transplant allocation policy: is the regional review board process fair?

Experienced transplant professionals may predict mortality better, in highly selected cirrhotic patients referred for accelerated listing to regional review boards, than the (Pediatric) Model for End-Stage Liver Disease score. However, these requests are often denied. We wished to establish if (1) such denials increase mortality and (2) referring physicians predict mortality better than the score. We analyzed 1,965 non-status 1 requests made between February and November 2002 from the United Network for Organ Sharing (UNOS) national scientific registry. Kaplan-Meier survival and time to transplant were compared between denied and approved patients. Cox proportional hazards analysis was used to establish if referring physicians predicted mortality better than the score. More requests were denied for patients with nonsanctioned conditions (45.7%) than for those with sanctioned conditions (13.3%); P less than.0001). Fewer patients denied accelerated listing had a transplant (46.6% vs. 63.8%; P <.0001); time to transplant was similar (P =.2). However, nonsanctioned cirrhotic cases denied accelerated listing had lower mortality than approved cases (P <.04). Referring physicians predict mortality poorly (P =.23), whereas the Model for End-Stage Liver Disease (MELD)-Pediatric Model for End-Stage Liver Disease (PELD) score was highly predictive (P =.0003). In conclusion, regional review boards are fair and can accurately distinguish high- from low-risk patients. Denying requests does not increase mortality. The MELD-PELD score remains the best predictor of mortality, but the review board process adds additional information. Referring physicians predict patient mortality poorly.