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K Rajender Reddy

Publications and source records attributed to K Rajender Reddy.

At least 19 recordsLinked to original sources
PubMed2007

Incidence and risk factors for weight loss during dual HIV/hepatitis C virus therapy.

BACKGROUND: Clinical observations suggest that patients with HIV/hepatitis C virus (HCV) may lose body weight during dual therapy, but this has not been confirmed analytically. OBJECTIVES: To determine if the incidence and degree of weight loss among patients with HIV/HCV receiving highly active antiretroviral therapy (HAART) and pegylated (PEG)-interferon plus ribavirin were greater than in (1) HCV-monoinfected patients receiving PEG-interferon plus ribavirin and (2) HIV-monoinfected patients receiving HAART. Risk factors for weight loss among patients with HIV/HCV were also examined. METHODS: A retrospective cohort study was performed among HIV/HCV-coinfected, HCV-monoinfected, and HIV-monoinfected patients. Body weights were assessed up to 6 months before and up to 12 months after initiation of HCV therapy (HIV/HCV-coinfected and HCV-monoinfected subjects) and over 18 months on HAART (HIV-monoinfected subjects). The primary outcome was clinically significant weight loss (> or =5% of baseline weight). RESULTS: Of 192 subjects, 63 had HIV/HCV, 64 had HCV alone, and 65 had HIV alone. Clinically significant weight loss occurred in 48 (76%) subjects with HIV/HCV versus 25 (39%) subjects with HCV (P < 0.001) and 2 (3%) subjects with HIV (P < 0.001), yielding adjusted hazard ratios (HRs) of 2.76 (95% confidence interval [CI]: 1.67 to 4.55) and 38.5 (95% CI: 8.5 to 174.7), respectively. Receipt of more than 2 nucleoside reverse transcriptase inhibitors increased the risk of clinically significant weight loss (adjusted HR = 8.17, 95% CI: 2.37 to 28.20). CONCLUSIONS: The incidence of weight loss is greater in dually treated patients with HIV/HCV than in treated HCV- or HIV-monoinfected patients. Prospective studies should evaluate additional risk factors for weight loss and changes in body composition to elucidate the mechanism for this weight loss.

Adult↗
PubMed2007

Comparison of clinical outcomes in chronic hepatitis B liver transplant candidates with and without hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) receive a higher MELD score and may undergo liver transplantation (OLT) earlier compared to patients with cirrhosis, potentially decreasing waiting list mortality. However, post-OLT survival may be reduced by recurrence of HCC. We compared clinical outcomes between patients with HBV-cirrhosis and no HCC and patients with HBV-HCC. A total of 279 patients (HBV-cirrhosis = 183; HBV-HCC = 96) in the US HBV-OLT study were followed for a median of 30.2 months from listing. Patients with HCC were older, more likely to be Asian, and had less severe liver impairment than patients with HBV-cirrhosis. Despite a higher rate of OLT in patients with HCC (78.1% vs. 51.4%; P < 0.001), intention-to-treat (ITT) survival (73% vs. 78%) and survival without OLT (82% vs. 79%) at 5 years were similar for patients with and without HCC. Cox regression analysis identified higher albumin, lower MELD, no HCC at listing, and being transplanted to be associated with better ITT survival. Ninety-four patients with HCC (including 19 new HCC) and 75 with HBV-cirrhosis underwent OLT. Post-OLT survival (83% vs. 90%) and HBV recurrence (11% vs. 10%) at 3 years were similar, while disease (HBV and/or HCC) recurrence (19% vs. 10%; P = 0.043) was higher in patients with HBV-HCC vs. HBV-cirrhosis. Disease recurrence was the only independent predictor of post-OLT survival. In conclusion, despite more advanced liver disease and a lower rate of transplantation, ITT survival of patients listed for HBV-cirrhosis was comparable to those with HBV-HCC, possibly related to beneficial effects of antiviral therapy.

Adult↗
PubMed2007

Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation.

In this retrospective study of hepatitis C virus (HCV)-infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.

Adult↗
PubMed2006

Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment.

BACKGROUND & AIMS: To maximize sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, treatment with pegylated interferon and ribavirin has been genotype-specific (1 vs non-1). We evaluated the effects of ribavirin and peginterferon alfa-2a dose reductions on SVR in patients infected with HCV genotype 1. METHODS: Data were pooled from 569 patients enrolled in 2 phase III trials of 48 weeks of treatment with peginterferon alfa-2a and ribavirin. All patients were evaluated for the effect of cumulative drug exposure on 4- and 12-week responses, and the 427 patients who completed treatment were evaluated for effect of drug exposure on SVR. RESULTS: Of patients who completed treatment, more had reductions (< or =97% cumulative dose) of ribavirin than of peginterferon alfa-2a (43% vs 27%). Neither early virologic response nor SVR was affected adversely by ribavirin reductions when the cumulative ribavirin exposure was greater than 60%. The SVR was reduced significantly (P = .0006) in patients with less than the 60% cumulative ribavirin dose and was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had minimal impact on SVR in patients who achieved rapid virologic response, defined as undetectable HCV RNA levels after 4 weeks, even when they received less than the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virologic response. CONCLUSIONS: Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR.

Adult↗
PubMed2006

Racial difference in mortality among U.S. veterans with HCV/HIV coinfection.

OBJECTIVES: This study was performed to examine the impact of viral coinfections and race on clinical and virological outcome of hepatitis C virus (HCV) infection. METHODS: Three groups of patients (265 HCV/HIV coinfected, 251 HCV monoinfected, 227 HIV monoinfected) were identified between 2000 and 2002 from the computerized patient record system at the Philadelphia VA Medical Center and analyzed for clinical and virological parameters. RESULTS: HCV/HIV coinfection was associated with higher frequency of liver function abnormalities (37% vs 21% vs 20%; p < 0.0003) and greater mortality (17% vs 6% vs 9% over 3 yr period, p = 0.0003, p = 0.027) compared to HCV or HIV monoinfection, respectively. However, HCV/HIV coinfection was not associated with worsened HIV-related parameters (CD4 count, HIV titer, and use of antiretroviral therapy) or increased HCV titers compared to HIV or HCV monoinfection in our population, respectively. Interestingly, mortality among HCV/HIV coinfected patients was significantly greater in white than in black patients (31% vs 15%, p = 0.011). This racial disparity in mortality was not apparent in the monoinfected groups and not explained by HBV coinfection or history of alcohol use disorder. CONCLUSIONS: We conclude that HCV/HIV coinfection is associated with worsened liver disease and higher mortality than HCV- or HIV-monoinfection without directly influencing CD4 count and HCV or HIV titers. Furthermore, we demonstrated a racial disparity in survival of HCV/HIV-coinfected patients that needs further investigation.

Alcoholism↗
PubMed2006

Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C.

BACKGROUND/AIMS: In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels. METHODS: Patients with chronic hepatitis C enrolled in three phase III clinical trials of peginterferon alfa-2a (40KD) plus ribavirin (two studies analysing 'elevated' and one persistently 'normal' alanine aminotransferase) were included. RESULTS: Multivariate analyses of 2,881 patients before treatment and of 1,403 patients with a sustained virological response indicated that gender, viral factors (genotype, HCV RNA titer) and indicators of metabolic syndrome (body mass index, blood pressure, blood glucose, cholesterol and triglyceride concentration) were associated with alanine aminotransferase levels. In addition, hepatitis C virus infection influenced serum lipids concentration according to a genotype-specific effect. CONCLUSIONS: Heterogeneity in alanine aminotransferase levels in patients with chronic hepatitis C partially depends on the degree of derangement of fat and carbohydrate metabolism. As this is the result of an interaction of chronic hepatitis C infection with the patient's individual characteristics, treatment decisions should not be based on alanine aminotransferase level alone but rather on global evaluation of the patient.

Alanine Transaminase↗
PubMed2006

Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy.

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon alpha-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA <50 IU/mL) and a SVR (HCV RNA <50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients with than without [corrected] a RVR (89% vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5; P < .0001) or 200,000-600,000 IU/mL (OR 5.6, 95% CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. > 600,000 IU/mL, 95% CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon alpha-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment.

Adult↗
PubMed2006

Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management.

Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time--INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation.

Blood Coagulation Disorders↗
PubMed2006

Protective antibody levels and dose requirements for IV 5% Nabi Hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B-induced end stage liver disease.

Lamivudine combined with Hepatitis B immune globulin (HBIg) prevents post liver transplant (LT) HBV recurrence. The study was designed to assess the impact of lamivudine on hepatitis B antibody (anti-HBs) and dosage requirements of intravenous 5% HBIg (Nabi-HB) in the first 36 weeks post LT. Adults undergoing LT for chronic HBV received lamivudine prior to or at LT, and IV HBIg 20,000 IU on day of LT, 10,000 on days 1-7, weeks 4 and 8, and 5,000 every 4 weeks thereafter. Replicative status based on serum HBV DNA (> 5 pg/mL = replicator (R) or < or = 5 pg/mL = nonreplicator (N) was determined at initiation of lamivudine (R or N) and within 2 weeks of LT (r or n), resulting in 3 groups: Nn, Rn, and Rr. Between December 1999 and May 2001, 30 patients (10 Nn, 13 Rn, 6 Rr, and 1 unknown), mean age of 52 years underwent LT. HBsAg neutralization was achieved with anti-HBs > 300 IU/L during week 1 and > 200 IU/L during weeks 2-12. All but one patient were HBsAg-negative on last follow-up. Pre-LT suppression of HBV replication resulted in similar dose requirements and pK in the Rn and Nn groups within 1 week after LT. Comparatively, the Rr group had greater HBIg requirements during weeks 1-12 due to greater anti-HBs clearance and shortened t(1/2) during the entire 36-week follow-up. In conclusion, this study provides a rationale for the use of lower HBIg doses in HBV patients with suppressed replication undergoing LT.

Adult↗
PubMed2006

Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era.

The potential for disease progression in patients awaiting liver transplantation for hepatocellular carcinoma (HCC) has encouraged many centers to employ pre-transplant radiofrequency ablation or chemoembolization in an attempt to control tumor burden while patients are on the wait list. Despite general acceptance by the transplant community, few objective data demonstrate pre-transplant treatment efficacy or improved post-transplant outcomes in HCC patients listed with Model for End-Stage Liver Disease (MELD) exception points. To evaluate the utility of pre-transplant therapy in the current MELD era, we retrospectively compared 31 treated patients (T) with 33 untreated (U) controls. Study endpoints included patient and disease-free survival, tumor recurrence, explant tumor viability, and the ability of MRI to detect viable tumor after therapy. Both cohorts had similar demographic, radiographic, and pathologic characteristics, although untreated patients waited longer for transplantation [119 (U) vs. 54 (T) days after MELD assignment, (P = .05); range: 1 day to 21 months]. Only 20% of treated tumors demonstrated complete ablation (necrosis) as defined by histologic examination of the entire lesion. Only 55% of lesions with histologic viable tumor were detected by MRI after pre-transplant therapy. After 36 months of follow-up, there was no difference between the treated and untreated groups in overall survival (84 vs. 91%), disease free survival (74% vs. 85%), cancer recurrence (23% vs. 12%), or mortality from cancer recurrence (57% vs. 25%) (P > 0.1). In conclusion, viable tumor frequently persists after pre-transplant locoregional therapy, and neoadjuvant treatment does not appear to improve post-transplant outcomes in the current MELD era.

Adult↗
PubMed2006

Evaluation of nonmalignant liver masses.

Nonmalignant liver masses are increasingly being recognized with the widespread use of imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging. The majority of these lesions are detected incidentally in asymptomatic patients. Based on the radiologic appearance, benign lesions can be categorized as solid or cystic, single or multiple, hypervascular or hypovascular. Based on histologic characteristics, they are classified as of hepatocellular, biliary, or mesenchymal origin. In the majority of patients, a proper diagnosis can be made based on these characteristics on imaging modalities alone. An invasive approach is seldom required. This review discusses the various characteristics of the most common benign liver lesions and recommends a practical approach.

Adenoma, Liver Cell↗
PubMed2006

Portal flow and arterioportal shunting after transjugular intrahepatic portosystemic shunt creation.

PURPOSE: It was postulated that a transjugular intrahepatic portosystemic shunt (TIPS) produces arterioportal shunting and accounts for reversed flow in the intrahepatic portal veins (PVs) after creation of the TIPS. This study sought to quantify this shunting in patients undergoing TIPS creation and/or revision with use of a direct catheter-based technique and by measuring changes in blood oxygenation within the TIPS and the PV. MATERIALS AND METHODS: This prospective study consisted of 26 patients. Median Model for End-stage Liver Disease and Child-Pugh scores were 13 and 9, respectively. Primary TIPS creation was attempted in 21 patients and revision of failing TIPS was undertaken in five. In two patients, TIPS creation was unsuccessful. All TIPS creation procedures but one were performed with use of polytetrafluoroethylene-covered stent-grafts. Flow within the main PV (Q(portal)) was measured with use of a retrograde thermodilutional catheter before and after TIPS creation/revision, and TIPS flow (Q(TIPS)) was measured at procedure completion. The amount of arterioportal shunting was assumed to be the increase between final Q(portal) and Q(TIPS), assuming Q(TIPS) was equivalent to the final Q(portal) plus the reversed flow in the right and left PVs. Oxygen saturation within the TIPS and the PV was determined from samples obtained during TIPS creation and revision. RESULTS: Mean Q(portal) before TIPS creation was 691 mL/min; mean Q(portal) after TIPS creation was 1,136 mL/min, representing a 64% increase (P = .049). Mean Q(TIPS) was 1,631 mL/min, a 44% increase from final Q(portal) (P = .0009). Among cases of revision, baseline Q(portal) was 1,010 mL/min and mean Q(portal) after TIPS revision was 1,415 mL/min, a 40% increase. Mean Q(TIPS) was 1,693 mL/min, a 20% increase from final Q(portal) (P = .42). Arterioportal shunting rates were 494 mL/min after TIPS creation and 277 mL/min after TIPS revision, representing 30% of total Q(TIPS) after TIPS creation and 16% of Q(TIPS) after TIPS revision. No increase in oxygen tension or saturation was seen in the PV or TIPS compared with initial PV levels. Q(TIPS) did not correlate with the portosystemic gradient. CONCLUSION: TIPS creation results in significant arterioportal shunting, with less arterioportal shunting seen among patients who undergo TIPS revision. Further work is necessary to correlate Q(TIPS) with the risk of hepatic encephalopathy and liver failure.

Adult↗
PubMed2006

Recurrence of diseases following orthotopic liver transplantation.

Long-term graft survival and mortality after liver transplantation continue to improve. However, disease recurrence remains a major stumbling block, especially among patients with hepatitis C. Chronic hepatitis C recurs to varying degrees in nearly all patients who undergo transplantation. Transplantation for hepatitis C is associated with higher rates of graft failure and death compared with transplantation for other indications, and retransplantation for hepatitis C related liver failure remains controversial. Recurrence of hepatitis B has been markedly reduced with improved prophylactic regimens. Further, rates of hepatocellular carcinoma recurrence have also decreased, as improved patient selection criteria have prioritized transplantation for those with a low risk of recurrence. Primary biliary cirrhosis recurs in some patients, but it is often relatively mild. Autoimmune liver disease has also been shown to have a relatively benign post-transplantation course, but some studies have indicated that it slowly progresses in most recipients. It has been recently reported that alcoholic liver disease liver transplant recipients who return to drinking have worsened mortality. In such patients worse outcomes are not due to graft failure, but instead to other comorbidities. Recurrences of other diseases, including nonalcoholic steatohepatitis and primary sclerosing cholangitis, are now being recognized as having potentially detrimental effects on graft survival and mortality. Expert clinical management may help prevent and treat complications associated with disease recurrence.

Carcinoma, Hepatocellular↗
PubMed2005

Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature.

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

Humans↗
PubMed2005

Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.

BACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

Adenine↗
PubMed2005

Reconstitution of hepatitis C virus-specific T-cellmediated immunity after liver transplantation.

Hepatitis C virus (HCV)-related liver failure is the leading indication for liver transplantation worldwide. After transplantation, virological recurrence is the rule, but the spectrum of histological injury is wide, ranging from the development of allograft cirrhosis within a few years to minimal hepatitis despite long-term follow-up. The immunological correlates of this variable natural history are poorly understood. Here, we studied the kinetics of the cellular immune responses, viral replication, and allograft histology in 24 patients who had undergone liver transplantation for HCV-related liver failure. Using direct ex vivo methodologies (i.e., interferon-gamma ELISPOT and major histocompatibility complex class I-peptide tetrameric complexes), we found that patients who experienced viral eradication after antiviral therapy showed restoration of HCV-specific T-cell responses, whereas patients with progressive HCV recurrence that failed to respond to therapy showed declining frequencies of these viral-specific effector cells. The cytotoxic T lymphocytes that peripherally reconstituted after transplantation were clonotypically identical to those present within the recipient explant liver, defined at the level of the T-cell receptor beta chain (one epitope/one clone). Moreover, the subset of patients who spontaneously demonstrated minimal histologic recurrence had more vigorous CD4+ T-cell responses in the first 3 months, particularly targeting nonstructural proteins. We provide evidence that T-cell responses emerge after liver transplantation, and their presence correlates with improved histological and clinical outcomes. In conclusion, these results may help identify patients more likely to develop severe HCV recurrence and therefore benefit from current antiviral therapy, as well as provide a rationale for the future use of novel immunotherapeutic approaches. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience. wiley.com/jpages/0270-9139/suppmat/index.html).

Adult↗
PubMed2005

T-cell response relative to genotype and ethnicity during antiviral therapy for chronic hepatitis C.

Viral genotype and host ethnicity are important predictors of viral clearance during antiviral therapy for chronic hepatitis C virus (HCV) infection. Based on the role of T cells in natural HCV clearance, we hypothesized that T cells may contribute to the genotypic and ethnic difference in treatment outcome. To test this hypothesis, T-cell response to HCV antigens (core, nonstructural NS3/4 and NS5) and control phytohemagglutinin (PHA) was monitored prospectively and was correlated with virological outcome in 41 patients chronically infected with HCV (27 genotype 1, 14 genotype 2 or 3; 19 black persons, 22 white persons) undergoing combined interferon alfa and ribavirin therapy. Interestingly, in patients with genotype 2 or 3 infection, enhanced virological response coincided with a greater T-cell response to HCV NS3/4 antigen at baseline (50% vs. 15%; P = .026) that augmented further during therapy (29% vs. 4%; P = .035) compared with genotype 1-infected patients. However, HCV-specific T-cell response remained weak in genotype 1-infected patients regardless of virological outcome or ethnicity. Furthermore, virological outcome was associated with a suppressed baseline proliferative response to phytohemagglutinin (P < .03) that increased during therapy (P < .003) independent of ethnicity or genotype. In conclusion, HCV-specific T-cell response was associated with HCV genotype but not with therapeutic clearance of HCV infection. The association between treatment outcome and phytohemagglutinin response suggests more global and antigen-nonspecific mechanisms for therapeutic HCV clearance.

Antiviral Agents↗