Tse-Ling Fong

Hepatitis C Virus Infection in Patients with B-Cell Non-Hodgkin Lymphoma

Hepatitis C virus (HCV) is the major etiologic agent of post-transfusion and sporadic non-A, non-B chronic hepatitis [1, 2]. Although HCV is a hepatotrophic virus, the HCV genome and its replicative intermediate have been detected in peripheral blood mononuclear cells in patients with chronic HCV infection [3]. The association between HCV and type II mixed cryoglobulinemia is unequivocal [4-6]. Antibodies to HCV (anti-HCV) and HCV RNA have been found in up to 98% of patients with mixed cryoglobulinemia [4], and approximately 36% of patients with chronic HCV infection have mixed cryoglobulinemia [7]. Of interest, mixed cryoglobulinemia is considered by some investigators [8, 9] to be a variant of low-grade B-cell non-Hodgkin lymphoma. Because HCV RNA can be detected in the peripheral blood mononuclear cells of patients with chronic hepatitis C [10], the persistence of HCV in these cells may chronically stimulate B-lymphocytes. This may cause clonal expansion of these immunoglobulin-secreting cells and eventually results in malignant B-cell lymphoproliferative diseases. Consistent with this hypothesis, chronic infection of B lymphocytes by a DNA parvovirus was shown to induce polyclonal and, later, monoclonal immunoglobulin production in minks [11]. On the basis of these observations, it has been hypothesized that chronic HCV infection, alone or in combination with other factors, may lead to the development of B-cell lymphoma. Several Italian studies [12-15] have reported a high prevalence (9% to 32%) of chronic HCV infection in patients with B-cell non Hodgkin lymphoma. However, data from the United Kingdom have not confirmed these observations [16, 17]. To determine the prevalence of HCV infection among patients with B-cell non-Hodgkin lymphoma in the United States, we did a controlled study of a large cohort of patients. Methods Patients Between October 1994 and May 1996, 120 consecutive patients with B-cell non-Hodgkin lymphoma were evaluated at the outpatient hematology clinic of the Los Angeles County-University of Southern California (LAC-USC) Medical Center. During the same period, we enrolled 268 additional patients as controls: 154 unselected patients with malignant hematologic conditions other than B-cell non-Hodgkin lymphoma who were seen at the same clinic (control group 1, which comprised 44 patients with acute leukemia, 45 with Hodgkin disease, 11 with T-cell lymphoma, 23 with chronic myelogenous leukemia, 20 with multiple myeloma, 10 with chronic lymphocytic leukemia, and 1 with hairy-cell leukemia) and 114 unselected patients without malignant hematologic conditions who were attending the general medicine clinic at LAC-USC (control group 2, which comprised 69 patients with systemic hypertension or ischemic heart disease, 35 with diabetes mellitus, and 10 with primary hypothyroidism). All potential study participants were tested for antibodies to HIV. Markers for HCV infection (anti-HCV and HCV RNA) and hepatitis B virus infection (hepatitis B surface antigen, antibodies to hepatitis B core antigen, and antibodies to hepatitis B surface antigen) were also determined. Patients who tested positive for antibodies to HIV (2 patients) or hepatitis B surface antigen (6 patients) were excluded. We did not exclude patients with known HCV infection or liver disease. Identical inclusion and exclusion criteria were used to enroll patients and controls. All patients were given a questionnaire that asked about demographic characteristics and potential risk factors for viral hepatitis and chronic liver disease. A patients ethnicity was determined on the basis of self-report. A liver panel, which included prothrombin activity and levels of alkaline phosphatase, albumin, globulin, total and direct bilirubin, lactic dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, was obtained for all patients at the time of evaluation. All patients gave written informed consent, and the study was approved by the institutional review board at LAC-USC Medical Center. Pathologic Evaluation of Lymphoma Lymphoma was diagnosed on the basis of morphologic evaluation of lymph node tissue or extranodal tissues, including bone marrow specimens. Immunophenotypic analysis for surface B- and T-lymphocytic markers was performed by using monoclonal antibodies, as described elsewhere [18, 19]. Non-Hodgkin lymphoma was graded by using the Modified Working Formulation classification [20, 21]. All slides were independently rereviewed by two expert hematopathologists who were not aware of the HCV infection status of the patients. Assessment of Hepatitis C Virus Infection We detected HCV antibodies by using a second-generation enzyme-linked immunosorbent assay (Anti-HCV EIA 2, Ortho Diagnostic Systems, Raritan, New Jersey). Blood samples for HCV RNA determination and HCV genotyping were processed and stored under the optimal conditions described by Davis and colleagues [22]. Serum HCV RNA was measured by a reverse-transcription polymerase chain reaction (RT-PCR) assay (Amplicor HCV test, Roche Molecular Systems, Somerville, New Jersey), as described elsewhere [23]. Briefly, total RNA was extracted from 100 L of serum with guanidinium thiocyanate and precipitated in isopropanol with poly(A) carrier RNA. An equivalent of 5 L of serum was reverse transcribed and amplified in a master mixture containing rTth DNA polymerase, biotinylated primers KY80 and KY78, buffer salts, unguentum, deoxyadenosine triphosphate, deoxycytidine triphosphate, 2-deoxyguanosine-5-triphosphate, and deoxyuridine triphosphate. Deoxyuridine triphosphate was incorporated into each amplification product to serve as a substrate for unguentum (AmpErase, Roche Molecular Systems); this prevented carryover contamination of previously amplified DNA. The reaction was optimized for the use of rTth that, in the presence of manganese, performs both reverse-transcription and DNA-polymerase functions. After RT-PCR was performed, biotin-labeled PCR products were chemically denatured; captured by a solid-phase, HCV-specific probe that was bound to microwell plates; and detected by using an avidin-horseradish peroxidase system with a conventional microtiter plate reader (450 nm). Optical density readings of more than 0.500 were considered positive for HCV, readings of less than 0.300 were considered negative, and readings of 0.300 to 0.500 were considered equivocal. We did HCV genotyping on all HCV RNA-positive specimens by using genotype-specific primers from the HCV core region under conditions described elsewhere [24]. Two rounds of amplification were done: We used genotype-nonspecific primers during the first round and genotype-specific primers during the second round. The amplification products were resolved on 2% agarose gels stained with ethidium bromide. Hepatitis C virus genotype was determined by genotype-specific bands of complementary DNA. Control samples of each detectable genotype (1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a) were evaluated in parallel. Radioimmunoassay (Ausria II, Abbott Laboratories, North Chicago, Illinois) was used to detect hepatitis B surface antigen and antibodies to hepatitis B surface antigen, and enzyme-linked immuno-assay (Corab, Abbott Laboratories) was used to detect antibodies to hepatitis B core antigen. Statistical Analysis The primary comparisons among groups for categorical variables were performed by using the Fisher exact test. We calculated the relative risk and 95% CIs that patients with HCV infection compared with patients without HCV infection would have extranodal lymphoma. We also computed 95% CIs for the prevalence of HCV infection in the B-cell lymphoma group and the two control groups. All CIs were calculated by using StatXact3 for Windows (Cytel Software Corp., Cambridge, Massachusetts). All other analyses were performed by using SAS 6.08 for Windows (SAS Institute, Inc., Cary, North Carolina). Results Patients in the B-cell lymphoma group and the two control groups were similar with respect to age, sex, ethnicity, and risk factors for viral hepatitis (Table 1). The prevalence of anti-HCV and HCV RNA in the three groups are shown in Table 2. Infection with HCV was detected in 26 of 120 patients with B-cell lymphoma (22% [95% CI, 15% to 30%]) compared with 7 of 154 patients (4.5%) in control group 1 and 6 of 114 patients (5%) in control group 2 (P < 0.001). Table 1. Demographic Characteristics of Patients with B-Cell Non-Hodgkin Lymphoma and Controls Table 2. Serologic and Virologic Markers in Hepatitis C Virus-Positive Patients* In the B-cell non-Hodgkin lymphoma group, both HCV RNA and anti-HCV were detected in 21 patients; HCV RNA was the only detectable marker in 4 patients, and HCV RNA was not detected in 1 anti-HCV-reactive patient. All control patients who were considered to be infected with HCV had detectable HCV RNA, although 3 of these patients were anti-HCV negative (Table 2). The most common HCV genotypes in patients with B-cell non-Hodgkin lymphoma were genotype 1a (12 of 26 patients [46%]), genotype 1b (8 of 26 patients [31%]), mixed genotype 1a and 1b (2 of 26 patients [8%]), and genotype 2b (2 of 26 patients [8%]) This incidence is similar to those reported elsewhere [25, 26] for patients with chronic HCV infection in the United States. Chronic liver disease had been diagnosed in 4 HCV-positive patients with B-cell lymphoma (15%) 2 to 6 years before lymphoma was diagnosed. Although 17 of 26 HCV-positive patients with lymphoma had increased aminotransferase activity, only 4 had levels of alanine aminotransferase or aspartate aminotransferase that exceeded 100 U/L. Similarly, most HCV-positive patients in the control groups had only mildly elevated aminotransferase levels. At least one percutaneous risk factor for HCV exposure was identified in 15 of 26 HCV-positive patients (58%) with B-cell non-Hodgkin lymphoma. The period during which patients were at risk for percutaneous exposure to HCV preceded th

Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C

BACKGROUND/AIMS The effects of corticosteroids on chronic hepatitis B have provided insight into the mechanism of liver cell injury caused by hepatitis B. In this study, this model was applied to investigate the effects of prednisone on alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels in chronic hepatitis C. METHODS Ten patients with chronic hepatitis C who had increased levels of ALT and HCV RNA detectable in serum were given a 7-week course of a tapering dose of prednisone. Quantitation of serum HCV RNA was determined by polymerase chain reaction (PCR) and by branched-chain DNA amplification. RESULTS ALT levels decreased in 8 of 10 patients during therapy. Mean ALT levels of all 10 patients decreased from 184 to 84 U/L (P = 0.002) and then rebounded in 7 of the 8 patients after discontinuation of prednisone. HCV RNA was detectable by the branched DNA technique in 9 of 10 patients. These values increased in all 9 patients during prednisone therapy. The mean serum HCV RNA levels increased from 40.9 before treatment to 414.3 Eq/mL x 10(5) during treatment (P = 0.043). Using PCR, HCV RNA titers increased one log-fold in 8 of 10 patients (geometric mean of 1:4420 to 1:23410). HCV RNA levels decreased to pretreatment values within a mean of 2.8 weeks (range, 1-5) after discontinuation of prednisone. CONCLUSIONS These responses in ALT and HCV RNA suggest the participation of an immune-mediated mechanism in the liver cell injury in chronic hepatitis C.

Severe Hepatotoxicity Associated with the Dietary Supplement LipoKinetix

Context Dietary supplements, unlike drugs, are not tightly controlled by the U.S. Food and Drug Administration (FDA) before marketing. Contribution LipoKinetix, a dietary supplement sold as an aid to promote weight loss, was associated with severe hepatotoxicity in seven previously healthy patients. None had evidence of viral infection or autoimmune disease or had ingested other hepatotoxic drugs. All patients recovered spontaneously after discontinuing use of LipoKinetix. Implications Although the FDA has issued warning letters to the manufacturer, physicians, and the public regarding LipoKinetix, federal oversight of dietary supplements remains problematic. Physicians should inquire about the use of dietary supplements when patients present with evidence of hepatotoxicity. The Editors Unlike licensed drugs, dietary supplements are not subject to review by the U.S. Food and Drug Administration (FDA) before marketing. Issues pertaining to the use of certain herbal products range from contamination with heavy metals (including lead, arsenic, and mercury) (1-3) to substitution of a product ingredient or misidentification of raw herbs that can result in toxicity (4). Hepatotoxicity has been associated with various herbal products (5, 6). LipoKinetix (Syntrax, Cape Girardeau, Missouri) capsules are sold as a dietary supplement for weight loss. In the United States,

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

33 billion is spent yearly on weight-loss products and services (7), despite the absence of scientific evidence in humans to support such use (8). According to the manufacturer, the purported mechanism of action of LipoKinetix is modifying a process in the body called oxidative phosphorylation that thereby mimics exercise. LipoKinetix contains the following ingredients: norephedrine hydrochloride (25 mg), sodium usniate (100 mg), 3,5-diiodothyronine (100 g), yohimbine hydrochloride (3 mg), and caffeine (100 mg). We describe seven patients who between July and December 2000 developed acute hepatitis, including one patient who developed fulminant hepatic failure complicated by cerebral edema, after ingesting LipoKinetix. Case Series Five patients (four women and one man) were treated at Cedars-Sinai Medical Center, Los Angeles, California, and two patients (both men) were identified through the FDA MedWatch program. All seven patients had taken LipoKinetix according to the manufacturers recommendations, and none were taking prescription or over-the-counter medications (including acetaminophen). No patient had a medical history, and none were obese. Results of serologic testing for hepatitis A, B, and C were negative in all patients. Results of autoimmune serologic testing (for antinuclear antibodies and antismooth-muscle antibodies) and results of testing for cytomegalovirus and EpsteinBarr virus were also negative in five patients who were tested. The five patients from Cedars-Sinai Medical Center were Japanese nationals residing in the Los Angeles area. They had purchased different lot numbers of the product at the same health food store. Symptoms appeared within 4 weeks after initial ingestion of LipoKinetix. The other two patients, identified from the MedWatch program, were white bodybuilders who were acquaintances and had purchased the product through the Internet. They sought medical attention at 9 and 12 weeks, respectively, after first taking LipoKinetix. It is unclear whether the lot numbers of the product used by these two patients differed. The clinical summary is presented in Table 1. Three of the seven patients, including the patient who developed fulminant hepatic failure, were taking only LipoKinetix at the time symptoms occurred (Table 2). Two of the four patients taking multiple supplements subsequently resumed taking supplements other than LipoKinetix without incident. Table 1. Patient Characteristics Table 2. Supplements: Use and Duration Case Report A previously healthy, 20-year-old female Japanese exchange student began taking LipoKinetix for weight loss 2 weeks before presenting with a low-grade fever, malaise, and worsening epigastric pain. She had jaundice, was alert and oriented, and did not have hepatosplenomegaly. Laboratory studies revealed an aspartate aminotransferase level of 49.64 kat/L (2978 U/L), alanine aminotransferase level of 47 850 nkat/L (2871 U/L), total bilirubin level of 222 mol/L (13.0 mg/dL), and international normalized ratio of 2.8. Aminotransferase levels continued to increase and peaked 5 days after the patient discontinued taking LipoKinetix. The patient became increasingly coagulopathic and developed stage 2 hepatic encephalopathy. She was evaluated for liver transplantation. With the subsequent development of stage 3 encephalopathy, the patient was intubated. Intracranial pressure was 35 mm Hg, and mannitol was administered. The intracranial pressure decreased with supportive care, and liver function test results improved over the next 6 days. On discharge, she had no neurologic sequelae and the international normalized ratio was normal. Aminotransferase levels returned to normal within 12 weeks. Analysis Three different lot numbers of LipoKinetix capsules were obtained from three patients treated at Cedars-Sinai Medical Center. The FDA analyzed these samples at Pacific Regional Laboratory SW (Los Angeles, California) using liquid chromatographyelectrospray mass spectrometry and Fourier transform infrared spectroscopy. Analyses confirmed that the product samples contained norephedrine, yohimbine, 3,5-diiodothyronine, sodium usniate (analyzed as usnic acid), and caffeine, as listed on the product label. No contaminants (including heavy metals) were detected. Discussion Unlike with licensed drugs, the safety of herbal products has relied on their traditional use and formulations for appropriate dosage, administration, and avoidance of harmful interactions. The dietary supplement market is a multibillion-dollar industry; use of herbal products has increased an estimated 380% from 1990 to 1997 (9). Competition has driven dietary supplement manufacturers to seek obscure ingredients and to use them in nontraditional ways and combinations. We report on seven healthy people who were not taking any prescription drugs and developed severe hepatotoxicity while taking LipoKinetix. All patients had used the manufacturers recommended dosages. Five patients had taken the supplement for 1 month or less, and two patients had used the product for 2 to 3 months. All presented with symptoms characteristic of acute hepatitis, including fatigue and abdominal pain. In addition, results of biochemical testing were consistent with acute hepatitis. The peak aminotransferase levels and pattern of liver test results were compatible with drug-induced acute hepatocellular necrosis. There was no evidence of allergy, such as rash or eosinophilia. Three patients developed significant jaundice, and one developed fulminant hepatic failure. All recovered spontaneously after discontinuing use of LipoKinetix, and results of liver tests as well as symptoms normalized within 4 months in five patients (two patients declined to have further testing). No other hepatotoxic agent or other cause for hepatotoxicity could be identified. Of the four patients taking multiple supplements, only one had taken multiple Chinese herbal formulations; however, none of the ingredients were associated with hepatotoxicity according to the Chinese Materia Medica, the standard reference for Chinese herbs (10). LipoKinetix-induced hepatotoxicity appears to be idiosyncratic (5, 11, 12). No published reports have described hepatotoxicity associated with any of the other individual substances contained in LipoKinetix. Ephedra alkaloids have been associated with multiple adverse cardiovascular and central nervous system events (13). Only a single reported case of acute hepatitis has been associated with Ephedra; however, that patient had taken numerous other products (14). The FDA notes relatively few cases of hepatitis or elevated aminotransferase levels associated with dietary supplements containing ephedrine alkaloids (approximately 25 of 1400 cases). These adverse event reports are often complex, with patients concurrently using many other products (dietary supplements and drugs), some of which have known hepatotoxic effects. Although a direct hepatotoxic effect has not been reported for ephedrine or norephedrine (also a metabolite of ephedrine), phenylpropanolamine (racemic norephedrine) has been reported to potentiate the hepatotoxicity of carbon tetrachloride and acetaminophen in mice (6, 15). Sodium usniate, the salt form of usnic acid, is a secondary metabolite found in several genera of lichens, including Usnea, Letharia, and Parmelia. Toxic reactions, including ataxia leading to paralysis and death, have been reported in animals ingesting lichens containing usnic acid; data in humans, however, are limited. Usnic acid uncouples oxidative phosphorylation in murine liver mitochondria, resulting in inhibition of adenosine triphosphate synthesis and enhancement of Mg 2+-adenosine triphosphate activity, which may contribute to hepatic toxicity (16). None of the seven patients, however, exhibited lactic acidosis, a typical feature of drug-induced liver injury due to mitochondrial dysfunction. Yohimbine is an indole alkaloid from the bark of the African Pausinystalia yohimbe tree and is also found in Rauwolfia root (17). The FDA has not evaluated yohimbine for safety or efficacy for any indication. It is widely touted as a remedy for male impotence, but the mode of action is by selective blockade of the presynaptic 2-receptor (17). Yohimbine penetrates the central nervous system and can stimulate mood and motor activity (17). Nausea, vomiting, abdominal pain, dizziness, and headache have been reported when yohimbine is used at therapeutic doses (17). Unintentional thyrotoxicosis factitia, a condition related to ingestion of exogenous thyroid hormone from adulterat

Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis

Background. There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). Methods. Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. Results. Renal half-life of KALT allografts was shorter than CLKT group (6.6±0.9 vs. 11.7±1.3 years, P<0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P<0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P<0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P<0.001). Conclusion. Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.

Hepatotoxicity Due to Hydroxycut: A Case Series

Autoimmune hepatitis is a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated with cyclosporine A. Cyclosporine A was started at 2–3 mg/kg/day and induced biochemical remission in four of five patients within 3 months. One of the four responders relapsed within 1 month of discontinuing cyclosporine on two occasions. Each time, liver tests promptly normalized after reinitiation of cyclosporine. Two responders were managed with cyclosporine alone. The single patient who did not respond to cyclosporine developed progressive liver failure, underwent orthotopic liver transplantation, and subsequently died of disseminated cytomegalovirus infection. Cyclosporine was generally well tolerated and none of the patients developed renal insufficiency. These data and review of 11 cases in the literature show that cyclosporine can induce remission of liver disease in patients with autoimmune hepatitis who are refractory to corticosteroids.

A pilot randomized, controlled trial of the effect of iron depletion on long-term response to α-interferon in patients with chronic hepatitis C

OBJECTIVES:Muscletech Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada) was a popular weight-loss supplement that was recalled by the manufacturer in May 2009 on the basis of reports of hepatotoxicity associated with this supplement. We sought to characterize the clinical presentation of Hydroxycut-associated liver injury and to adjudicate these cases for causal association with Hydroxycut.METHODS:We assessed the causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study.RESULTS:Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized, and three of eight patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed eight cases as definite, five highly likely, two probable, and two were considered to be possible.CONCLUSIONS:Hydroxycut has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight-loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation.

Abstract Background/Aims: Some studies have suggested that hepatic iron may influence the response to interferon therapy in chronic hepatitis C patients. We conducted this randomized, controlled trial to evaluate the effect of iron depletion on: (1) aminotransferase activity and hepatitis C RNA levels; and (2) response to interferon therapy in 38 patients with elevated alanine aminotransferase levels and who were HCV RNA positive. Methods: Seventeen patients underwent a 500-ml phlebotomy every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of α-interferon 2b (3 mu tiw). Controls were 21 patients who were monitored for 6- to 8-week period without phlebotomy prior to interferon therapy. Response to interferon was defined as loss of serum HCV RNA by reverse transcriptase-polymerase chain reaction. Serum HCV RNA was quantitated by bDNA technique. Results: Alanine aminotransferase levels decreased in 1517 patients after phlebotomy. Mean alanine aminotransferase fell from 156.8 to 89.7 U/l ( p =0.008). Changes in iron indices and alanine aminotransferase after phlebotomy were not accompanied by changes in HCV RNA levels. In control patients, neither alanine aminotransferase nor HCV RNA levels changed during the observation period. At the end of 24 weeks of interferon therapy, sol:717 phlebotomized patients had a response, compared to 621 control patients ( p =ns). After 6 months of follow-up, 517 phlebotomized patients remained HCV RNA negative, in contrast to only 121 controls ( p =0.07). Conclusions: Iron depletion led to a reduction in aminotransferase levels; this was not accompanied by changes in levels of hepatitis C RNA. There may be an improvement in the sustained response to interferon therapy, but this requires confirmation.

Hyperthyroidism and hepatic dysfunction : a case series analysis

Background. Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. Methods. From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. Results. Graft and patient survival rates were lower among LKT recipients compared with KAT (P <0.001) and PKT recipients (P <0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P =0.005 vs. KAT, P =0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P <0.0001). Conclusions. Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.

Spontaneous reactivation in chronic hepatitis B: Patterns and natural history

Liver dysfunction in hyperthyroid patients has not been well characterized. We analyzed the clinical records of 43 patients with hyperthyroidism to define the spectrum of clinical and liver test abnormalities. The patients were divided into three categories: (a) 18 patients with uncomplicated hyperthyroidism (HT) (b) 19 with hyperthyroidism and congestive heart failure (HT/CHF), and (c) 6 with hyperthyroidism and concomitant unrelated liver disease (HT/ULD). Hepatomegaly and/or spenomegaly were noted in 15 of 19 (79%) patients with HT/CHF as compared to 6 of 18 (33%) patients with HT and 3 of 6 (50%) patients with HT/ULD. Four patients with HT/CHF had ascites. Serum aminotransferase levels > 250 IU/L were noted in only 1 of 37 (3%) patients without unrelated liver disease. Patients with HT/ULD or HT/CHF had markedly low prothrombin time. Serum bilirubin levels as high as 323