Impact of untreated portal vein thrombosis on pre and post liver transplant outcomes in cirrhosis.

BACKGROUND AND AIMS: Most portal vein thromboses (PVT) in cirrhotics are discovered incidentally. While case series demonstrate improved portal vein patency with anti-coagulation, there is little information on impact of PVT on morbidity and mortality. This study aimed to compare morbidity and mortality in cirrhotics with untreated PVT with those without PVT. MATERIAL AND METHODS: Cirrhotics evaluated for orthotopic liver transplant in a single large transplant center were prospectively followed. Subjects had contrast CT or MRI at initial evaluation and serial imaging every 6 months until transplantation, removal from the list or death. Univariate and multivariate Cox regression analysis were used to assess associations between new PVT and factors of interest. RESULTS: Of the 290 prospectively followed cirrhotics who met inclusion criteria, PVT was detected in 70 (24.1%)-47 had PVT at the time of initial evaluation and 23 developed one during the pre-transplant study period. A third of the patients with PVT had re-canalization or spontaneous resolution of thrombus while awaiting transplantation. There was no difference in the pre or posttransplant mortality between cirrhotics with and without PVT. CONCLUSION: Cirrhotics with untreated PVT fared equally well as those without PVT before and after transplantation. Further studies with larger numbers of patients are needed to determine if anticoagulation therapy truly improves outcomes in cirrhotics with portal vein thrombosis.

Metabolic syndrome and liver transplantation.

Non-alcoholic fatty liver disease (NAFLD), an important consequence of the global epidemic of obesity, is a common indication of orthotopic liver transplantation in the western world. Currently, NAFLD is the fourth most common indication of liver transplantation in the United Stated with prediction for increase demand of liver transplantation for NAFLD cirrhosis in the next two decades to exceed that of liver transplantation for chronic hepatitis C virus infection. Given the advances in the efficacy and tolerability of immunosuppressive agents which have reduced the incidence of chronic rejection, long-term survival rates after liver transplantation have remarkably improved. Today, long-term graft loss and death after liver transplantation are commonly related to age-related complications, such as cardiovascular disease. Features of metabolic syndrome including obesity, hypertension, hyperglycemia and dyslipidemia are very prevalent and almost universal after liver transplantation. These metabolic derangements are intricately associated with cardiovascular events and have emerged as the leading cause of morbidity and mortality after liver transplantation. In addition, the international epidemic of obesity has negatively impacted the liver transplant candidacy. Because obesity is associated with poor postoperative outcome, many transplant centers decline liver transplantation for morbidly obese individuals above certain level of body mass index.

De Novo Autoimmune Hepatitis Following Liver Transplantation.

INTRODUCTION: De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. METHODS: Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies. RESULTS: A total of 30 patients with plasma cell hepatitis were identified. Underling liver disease were hepatitis C virus (n = 11) and non-hepatitis C virus-related disease (n = 19). The interval period from liver transplantation to development of plasma cell hepatitis was 20 (2-246) months during 6 (1.5-25.8) years after liver transplantation. The mean international autoimmune hepatitis score and frequency of acute cellular rejection episode prior to the diagnosis of plasma cell hepatitis were lower in the patients with hepatitis C virus than those underlying non-hepatitis C virus-related disease. Twenty-seven patients (90.0%) showed complete biochemical response to plasma cell hepatitis treatment, but 10 (37.0%) patients relapsed. During the median 72 months' follow-up after liver transplantation, 9 (30.0%) patients progressed to cirrhosis (median 37 months) and 10 (33.3%) patients died or were retransplanted. CONCLUSIONS: This long-term clinical observation shows that de novo autoimmune hepatitis represents one cause of graft loss in patients with or without hepatitis C virus. Although most patients exhibit a good response to medical therapy, de novo autoimmune hepatitis is likely to recur and progress to liver cirrhosis.

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and binary (approximately 50 kD) complexes was also determined to assess IGF bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the approximately 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis.

Liver Transplantation for Hepatitis B in Early Adulthood: Analysis of the United Network for Organ Sharing Database.

BACKGROUND: Chronic hepatitis B virus (HBV) infection has a mild course in most children that may delay initiation of treatment even when indicated. Unfortunately, a small number of cases can progress rapidly to cirrhosis, which may require liver transplantation (LT) in early adulthood. The aim of this study was to assess the characteristics of HBV-positive young adults who received LT and to evaluate post-transplant outcomes including patient and graft survival and differences between pre- and post-implementation of Model for End-stage Liver Disease (MELD) prioritization. METHODS: The United Network for Organ Sharing (UNOS) database review was conducted from 1987 to 2012, and a retrospective analysis was performed on all young adult patients (ages 18-35 years) who underwent LT in the United States with a primary diagnosis of HBV or were seropositive for HBV surface antigen at time of LT. Kaplan-Meier analysis was used to assess patient and graft survival in the pre-MELD and post-MELD eras. Factors associated with survival were identified through the use of Cox regression analysis. RESULTS: A total of 522 HBV-infected subjects were included. Average age at time of transplant was 28.4 ± 5.2 years; 60.9% were male, 48.6% were white, the mean body mass index was 25 ± 5.5 kg/m2, diabetes was present in 3.9%, hepatocellular carcinoma (HCC) was present in 4.4%, and 10.4% were on dialysis prior to LT. Median follow-up after first LT was 48.2 months [12.5, 109]. During this time, 174 (33.3%) patients died with a mean age at the time of death of 31.6 ± 7.8 years, including 144 of 522 (28%) after the first LT, 26 of 74 (35%) after the second LT, and 4 of 12 (33%) after the third LT. The most common cause of death was graft failure (27.6%), followed by infection (16.6%). Overall, only 58% of patients were alive with their first LT at last follow-up. Kaplan-Meier analysis revealed worse patient and graft survival after re-transplantation in comparison to initial LT. Three hundred thirty subjects were transplanted in the pre-MELD era and 192 were transplanted in post-MELD era. Obesity, HCC, shorter ventilation use, shorter cold ischemia time, and non-white donor race were significantly more common in the post-MELD era (all with P < .05). Importantly, 5-year patient and graft survival rates were higher in the post-MELD era compared with the pre-MELD era. CONCLUSIONS: LT in young adults for HBV has poor outcomes and can be associated with premature death. These findings should prompt more aggressive evaluation and treatment for HBV in young patients. Superior outcomes in the post-MELD era compared with the pre-MELD era may be attributed to pre-transplant factors, improved surgical technique, and better treatment options for HBV infection.

Sofosbuvir and Simeprevir for the Treatment of Recurrent Hepatitis C with Fibrosing Cholestatic Hepatitis after Liver Transplantation.

Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT), which frequently results in graft failure and death. Treatment of FCH remains challenging, and the optimal antiviral therapy is yet to be determined. Between November 2013 and early 2015, 62 patients with HCV cirrhosis underwent OLT at our transplant center, of whom, 5 patients developed recurrence HCV in the form of severe FCH and were treated with sofosbuvir and simeprevir (SOF-SMV) for 24 weeks. All patients achieved significant improvement of HCV viral load and had undetectable viral PCR at 6-8 week of treatment. The HCV RNA remained undetectable throughout treatment course. The first two patients achieved SVR at week 12 after completion of the treatment. There were significant histologic and biomarkers improvements after initiation of the treatment. One patient developed refractory pruritus and acute pancreatitis. The second, fourth and fifth patients had very benign treatment courses with no side effects recorded. The third patient was starting the treatment with multiple comorbid conditions. His course was complicated with hepatic artery thrombosis, and later developed sepsis and renal failure. Therefore, it seems that the combination of SOF-SMV is an efficacious oral regimen in OLT recipient with recurrent hepatitis C and FCH. However, safety profile needs to be carefully evaluated.

Monitoring serial CD4⁺ T-cell function after liver transplantation can be used to predict hepatocellular carcinoma recurrence.

BACKGROUND: After liver transplant (LT), the risk of hepatocellular carcinoma (HCC) recurrence is partially dependent on the degree of immunosuppression. We aimed to determine whether assessing net state of CD4(+) T-cell function after LT could determine those at risk for HCC recurrence. METHODS: One hundred thirty-seven patients with cirrhosis who underwent LT for HCC were followed for recurrence of HCC. All patients had serial CD4(+) assay performed prospectively. Cox regression analysis was used to assess factors associated with HCC recurrence. Kaplan-Meier plots were used to assess the association between CD4(+) ATP values and hazard of HCC recurrence. RESULTS: The mean follow-up time was 3.1 ± 1.5 years, during which 14 patients (10%) had HCC recurrence. Patients with combined post-LT CD4(+) T-cell function area under curve (AUC) <675 had 6.9 (95% CI 2.0-22.0) times greater hazard of HCC recurrence than those with CD4(+) T-cell function AUC ≥675 (P < .001). Less immunosuppression (ATP AUC ≥675) in those beyond Milan conferred a similar risk of recurrence as patients transplanted within Milan (P = .064). CONCLUSION: Lower cumulative CD4(+) T-cell function post-LT predicted a higher risk of HCC recurrence. These findings may have implications toward management of HCC patients after LT.

Treatment of Recurrent Hepatitis C Genotype-4 Post-Liver Transplantation with Sofosbuvir plus Simeprevir.

Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4-the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12-24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.

Safety and efficacy of hepatitis A vaccination in liver transplantation recipients.

OBJECTIVE: Vaccination against hepatitis A (HAV) has been shown to be safe and effective in healthy subjects and in patients with chronic liver disease (CLD). The safety and efficacy of HAV vaccines in liver transplant (OLT) recipients have not been established. The objective of this study is to assess the safety and efficacy of inactivated hepatitis A vaccine in OLT recipients. METHODS: Thirty-seven HAV seronegative OLT recipients were enrolled. Patients received two doses of vaccine 6 months apart. Postvaccination IgG anti-HAV were determined at 1, 6, and 7 months after the first vaccine dose. Side effects were monitored for 3 days after each vaccination shot. An unvaccinated control group (45 patients) was followed for evidence of seroconversion. Seroconversion rate was also compared with those reported in healthy patients and in patients with chronic liver disease. RESULTS: Testing was available for all the cases at 1 month, and for 26 and 23 patients at 6 and 7 months, respectively. Only 3 of 37 patients (8%) had seroconversion at 1 month. At 6- and 7-month time points, 5 of 26 (19%) and 6 of the 23 (26%) patients had seroconversion, respectively. Vaccine responders had higher total white blood cell count and lymphocyte count and were further out from transplant compared with nonresponders. None of the unvaccinated patients had seroconversion over the follow-up time. Seroconversion rates in OLT recipients were significantly lower than that reported in healthy individuals (P=0.001) or in pre-OLT patients with CLD (P=0.001). All patients tolerated the vaccine well. CONCLUSIONS: HAV vaccination is safe in OLT recipient. Efficacy of HAV vaccination in OLT recipients, as measured by a commercially available enzyme immunoassay, is low and alternative strategies should be developed to improve response rate.

Relationship between hepatitis C genotype and severity of recurrent hepatitis C after liver transplantation.

BACKGROUND: Recurrence of hepatitis C virus (HCV) infection after liver transplantation is universal, but the relationship between hepatitis C genotype and posttransplant outcome has been controversial. The aim of this study was to assess the relationship between hepatitis C genotype on posttransplant frequency of recurrent hepatitis, histologic severity of recurrence, and progression to cirrhosis. METHODS: We studied 42 HCV RNA positive patients who received transplants between 1985 and 1994. Sera were tested for HCV RNA and protocol liver biopsies were in obtained the posttransplant period. Biopsies were scored according to the histologic activity index (HAI) and staged in a blinded fashion. RESULTS: The distribution of hepatitis C genotypes distribution was as follows: 1a, 19 (45%); 1b, 17 (40%); 2b, 3 (7%); and 1 each of 2a, 3a, and 4a. There was histologic evidence of hepatitis in 38 of 42 (90.4%) of patients. Hepatitis C was mild, moderate, or severe (HAI>3) in 38% of grafts and minimal (HAI 0-3) in 62%. Overall HAI scores and histologic stage were higher in the genotype 1b group. Six of 17 (35%) genotype 1b patients had cirrhosis compared with 2 of 25 (8%) in the non-1b genotype group. CONCLUSIONS: (1) Histologic evidence of recurrent hepatitis C is seen in 90% of liver allografts; (2) Histologic hepatitis C recurs with similar frequency in genotype 1b and non-1b recipients; (3) Genotype 1b is associated with more severe histologic disease recurrence than non-1b genotypes; (4) Genotype 1b appears to be associated with a higher degree of posttransplant fibrosis and cirrhosis than non-1b genotypes.

Experimental and emerging therapies for chronic hepatitis C virus infection.

Hepatitis C virus infection is prevalent throughout the world and is associated with substantial morbidity, mortality and health economic burden. No effective preventative measure, including vaccination, is currently available. Incremental and substantial progress in the rate of viral eradication using interferon-based therapies has been made over the past decade. The most recent advance has been related to the development of a pegylated form of IFN-alpha by two independent pharmaceutical companies. Pegylation of IFN-alpha appears to prolong its half-life, allowing for less frequent dosing. Reports have suggested that pegylated interferons are also associated with better efficacy for viral eradication in patients with hepatitis C virus. Slower progress also has been made in developing non-interferon-based therapeutic agents against hepatitis C virus, including protease inhibitors, helicase inhibitors, ribozymes, antisense therapies, cytokine-based therapies and T-cell-based therapeutic vaccines.

Hepatitis C genotypes: current trends and future implications.

OBJECTIVE: To review the geographic distribution and current understanding of hepatitis C virus (HCV) genotypes in regard to liver disease activity and response to treatment. MATERIAL AND METHODS: We review the relevant medical literature and discuss our recent findings relative to chronic HCV infection and the importance of HCV genotypes. RESULTS: HCV genotypes 1a and 1b are the most commonly found genotypes in patients with chronic HCV in the United States. Infection with HCV genotype 1b may be associated with more severe liver disease and may have a higher risk for the development of hepatocellular carcinoma. HCV genotype 2b seemed to be the most sensitive and HCV genotype 1b was the least sensitive to interferon therapy. CONCLUSION: The identification of the infectious HCV genotype may be beneficial in clinical settings and may assist in the selection of patients who would benefit from interferon treatment.

Advances in the molecular diagnosis of hepatitis C and their clinical implications.

Serologic assays for diagnosis of hepatitis C infection may yield indeterminate results despite improvements in sensitivity and specificity through second- and third-generation assays. Direct detection of hepatitis C virus (HCV) RNA based on qualitative reverse transcription-polymerase chain reaction or transcription-mediated amplification allows diagnosis in the early stages of acute infection and in patients unable to mount an antibody response. Quantitative HCV RNA assays are useful for selecting appropriate antiviral therapies, but until recently they have lacked comparability between tests. More sensitive qualitative assays should be used for determining duration of treatment or recognizing a sustained virologic response to therapy. Hepatitis C virus genotyping can be performed from a limited sequence analysis of the viral genome by using various techniques. Although newer genotyping methods are relatively practicable and are satisfactory for the discrimination of the majority of genotypes, discrimination between subtypes can be challenging. Serologic typing of HCV lacks sensitivity and specificity compared with molecular-based techniques. Recent advances in serologic assays and nucleic acid detection techniques allow physicians to make accurate diagnoses, and these assays serve as important tools in treatment planning.

Gastroesophageal reflux in infants and children.

Gastroesophageal reflux is a common pediatric complaint and a frequent reason for pediatric patients to be referred to a gastroenterologist. The pathophysiology and clinical manifestations of this disorder differ according to patient age. The diagnosis is suggested by the history and can be confirmed by a pH probe. In the appropriate clinical setting, anatomic obstruction may need to be ruled out by contrast study. Endoscopy is used to assess associated complications, including esophagitis, esophageal strictures, Barrett's transformation, and failure to thrive. Other complications are controversial, including pulmonary disease, apnea, and sudden infant death syndrome. Treatment depends on the severity of disease. Conservative therapy includes behavorial modifications, prokinetic agents, and H2 antagonists. Proton pump inhibitors are generally reserved for refractory esophagitis. Surgical treatment may be necessary for gastroesophageal reflux resistant to medical management or for severe complications. Gastroesophageal reflux beyond infancy tends to be chronic; therefore, lifelong behavioral modifications or repeated courses of medical therapy may be necessary. An algorithm for the suggested diagnostic approach to gastroesophageal reflux is presented herein.

Genotype-dependent serologic reactivities in patients infected with hepatitis C virus in the United States.

OBJECTIVE: To evaluate the serologic reactivities in patients infected with different hepatitis C virus (HCV) genotypes to four HCV proteins that are components of the second-generation recombinant immunoblot assay. MATERIAL AND METHODS: Serum samples from 36 patients with chronic HCV infection were obtained. RNA was extracted by using chaotropic lysis and isopropanol precipitation. Reverse-transcriptase polymerase chain reaction of the NS-5 region was performed, followed by automated single-pass dideoxy sequencing of desalted amplification products. Classification of isolated HCV subtypes was based on Simmonds' system. All samples were tested for antibodies to proteins 5-1-1, C100-3, C33c, and C22-3 with the second-generation recombinant immunoblot assay. RESULTS: Reactivity to protein 5-1-1 was significantly lower for patients with genotypes 2b and 3a than for those infected with HCV types 1a or 1b (P < 0.05). Antibody reactivity to the C100-3 protein was also reduced in patients infected with HCV types 2b and 3a. CONCLUSION: These data indicate that the genotype-dependent differences in serologic reactivities are substantial among patients with chronic HCV infection.

Viral genotypes as determinants of autoimmune expression in chronic hepatitis C.

OBJECTIVE: To correlate viral genotypes with the immune manifestations of chronic hepatitis C and evaluate the effect of immune features on disease expression and response to antiviral treatment. DESIGN: We undertook a retrospective analysis of 67 patients with chronic hepatitis C. MATERIAL AND METHODS: Patients were selected for study if they had been screened for autoantibodies and concurrent immune diseases and if viral genotyping had been performed or was possible. Concurrent immune manifestations and responses to interferon therapy were determined. RESULTS: Of the 67 patients, 18 (27%) had one or more immune features. Immune manifestations occurred as commonly in patients with genotype 1 as in those with other genotypes (30% versus 14%; P = 0.3). Concurrent immune features did not distinguish patients, and responses to interferon therapy were similar between patients with and those without immune manifestations. None of the 14 patients with concurrent immune diseases or high-titer autoantibodies (serum titers, 1:320 or more) entered remission during interferon treatment. In contrast, 6 of 53 patients without concurrent immune diseases and no or low-titer autoantibodies had treatment-related remission. These differences, however, were not statistically significant (0% versus 11%; P = 0.3). CONCLUSION: Autoantibodies and concurrent immune diseases are not associated with a particular viral genotype, clinical profile, or treatment outcome. Larger studies are necessary for complete assessment of the influence of prominent immune manifestations on treatment response.

Clostridium difficile-associated diarrhea and colitis.

Clostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea and colitis, typically after the use of broad-spectrum antibiotics. The clinical presentation ranges from self-limited diarrhea to fulminant colitis and toxic megacolon. The incidence of this disease is increasing, resulting in major medical and economic consequences. Although most cases respond quickly to medical treatment, C difficile colitis may be serious, especially if diagnosis and treatment are delayed. Recurrent disease represents a particularly challenging problem. Prevention is best accomplished by limiting the use of broad-spectrum antibiotics and following good hygienic techniques and universal precautions to limit the transmission of bacteria. A high index of suspicion results in early diagnosis and treatment and potentially reduces the incidence of complications.

GB virus-C infection in type 1 autoimmune hepatitis.

OBJECTIVE: To assess the frequency and significance of GB virus-C infection in type 1 autoimmune hepatitis. MATERIAL AND METHODS: Serum specimens from 94 patients with type 1 autoimmune hepatitis were tested for GB virus-C RNA by reverse transcription and polymerase chain reaction. Serum samples from 50 normal subjects were also assessed. RESULTS: Three of the 94 specimens from patients with autoimmune hepatitis were positive for GB virus-C RNA in comparison with none of the 50 control samples (3% versus 0%; P = 0.5). Two patients were seropositive after variceal hemorrhage and blood transfusion, including one patient who clearly acquired the infection in this fashion. One patient had no epidemiologic basis for his seropositivity. Viremia was prolonged in all infected patients (mean duration, 69 +/- 23 months; range, 36 to 113); however, no clinical features suggested a concurrent viral infection, and mortality was similar to that among the uninfected counterparts (33% versus 8%; P = 0.2). Liver transplantation was more common in the infected patients (67% versus 9%; P = 0.03), but the duration of disease was also longer in these patients (277 +/- 29 months versus 106 +/- 9 months; P = 0.0008). Clinical features and immediate responses to corticosteroid therapy were similar in both groups. CONCLUSION: GB virus-C RNA is found infrequently in type 1 autoimmune hepatitis, and GB virus-C is unlikely to be an important etiologic agent or prognostic determinant.

Prevalence and outcome of hepatitis C infection among heart transplant recipients.

BACKGROUND: Hepatitis C virus infection is common in organ transplant recipients, and can be associated with significant morbidity and mortality. A unique feature of this infection among immunosuppressed patients is that it can progress without the development of hepatitis C virus antibodies. METHODS: To define the prevalence of hepatitis C virus infection in patients undergoing heart transplantation and identify clinical syndromes associated with hepatitis C virus infection in heart transplant recipients, we collected sera from 59 consecutive heart transplant recipients and their donors. Samples were tested before and after transplantation for hepatitis C virus antibodies with the use of a second-generation recombinant immunoblot assay and for hepatitis C virus RNA by means of reverse transcriptase polymerase chain reaction. RESULTS: Four of 59 patients (7%) had hepatitis C virus-RNA detected in posttransplantation serum samples; but only one of these was anti-hepatitis C virus antibody positive. Two of the four patients with hepatitis C virus RNA detected after transplantation received organs from donors who were positive for hepatitis C virus RNA/anti-hepatitis C virus. One of these two recipients tested positive for hepatitis C virus antibody and hepatitis C virus RNA before transplantation. The other two patients received organs from hepatitis C virus negative donors and possibly acquired infection after transplantation from blood or immunoglobulin preparations. One patient was anti-hepatitis C virus positive before transplantation but had no detectable hepatitis C virus RNA, and hepatitis C virus infection did not develop after transplantation. Progressive hepatitis C virus-induced cholestatic liver disease that led to hepatic failure and death after heart transplantation occurred in one of the four patients. CONCLUSION: Hepatitis C virus infection may occur after heart transplantation in the absence of anti-hepatitis C virus antibodies, and a syndrome of severe cholestatic liver disease may complicate heart transplantation in the presence of hepatitis C virus infection.

Hepatitis C virus genotypes and hepatitis G virus in hemodialysis patients from Syria: identification of two novel hepatitis C virus subtypes.

High prevalence of hepatitis C (HCV) and hepatitis G (HGV) viruses has been reported among hemodialysis patients with substantial heterogeneity of HCV genotypes throughout the world. We studied HCV prevalence, clinical significance, genotype distribution, and HGV coinfection in hemodialysis patients from Syria. Ninety (75%) of 120 screened patients were HCV antibody positive. Forty-nine (87.5%) of 56 HCV antibody-positive patients had HCV RNA detected by the polymerase chain reaction. The HCV genotyping was possible in 37 of 49 patients (76%). The HCV genotype distribution was genotype 1a, seven (19%); genotype 1b, 10 (27%); genotype 4a, 11 (30%); unmatched sequences, nine (24%). Phylogenetic analysis of unmatched sequences indicated that they represent two distinct and novel subtypes of HCV genotype 4. Hepatitis G virus RNA was detected in 29 (59%) of the HCV RNA-positive patients. No differences were identified between patients infected with HCV alone and those coinfected with HGV. These data demonstrate that HCV infection is common in this population with a genotype distribution predominantly made up of types 1 and 4. Coinfection with HGV had no effect on the outcome of HCV infection.