Hepatitis: Rustgi VK

Shiffman ML, Rustgi VK. · No affiliation provided · Gastroenterology. · Pubmed #17030201 No free full text.

This publication has no abstract.

Kotlyar DS, Blonski W, Rustgi VK. · University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Clin Liver Dis. · Pubmed #18625428 No free full text.

Abstract: Noninvasive approaches in the diagnosis and monitoring of fibrosis are still evolving. Transient elastography is an inexpensive, rapid, and relatively accurate form of noninvasive monitoring, especially in severe fibrosis It is a nascent technology, however, and there is no clear indication that elastography is better than biopsy for less severe fibrosis. With improved resolution and longer term data, it may become a vital supplement. The combined use of transient elastography and biochemical markers seems to be the most promising noninvasive technique.

Rustgi VK. · Transplant Institute, Georgetown University Medical Center, 8316 Arlington Blvd., Ste 515, Fairfax, VA 22031, USA. · J Gastroenterol. · Pubmed #17653645 No free full text.

Abstract: BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in the United States has remained constant from 1988 through 2002, although the peak age of infection has increased. While the number of new HCV cases is declining, the rates of HCV-associated morbidity and mortality are increasing. We reviewed the risk factors for HCV infection, the laboratory methods used to diagnose it, the dynamics of disease progression, and the natural history of HCV infection. METHODS: Medline searches were performed using the key word HCV, together with incidence, risk factors, demographics, diagnostic methods, disease progression, natural history, normal alanine aminotransferase (ALT), fibrosis, and hepatocellular carcinoma (HCC). RESULTS: Three characteristics-abnormal serum ALT, history of injection drug use, and blood transfusion before 1992-identified 85% of HCV-positive individuals 20-59 years old. About 75%-85% of acutely infected individuals progress to chronic infection, with up to 20% developing liver cirrhosis over 20-25 years, putting them at increased risk for end-stage liver disease and/or HCC. HCV-associated cirrhosis is the leading cause of liver transplantation in the United States. Rates of infection are higher in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans and higher in men than in women. In the United States, over 70% of HCV-infected individuals are infected with genotype 1. CONCLUSIONS: HCV infection is more prevalent than human immunodeficiency virus or hepatitis B virus infection and is particularly common among certain demographic groups. Individual rates of fibrosis progression vary, but identification of host and viral characteristics associated with disease progression may reveal the mechanisms of HCV-associated hepatic fibrosis/cirrhosis.

Rustgi VK. · Transplant Institute, Georgetown University Medical Center, Fairfax, VA 22031, USA. · Expert Rev Anti Infect Ther. · Pubmed #16307501 No free full text.

Abstract: Approximately 50% of treatment-naive hepatitis C patients fail to achieve a sustained virologic response with standard peginterferon and ribavirin therapy. Patients who are infected with genotype 1 have high viral loads and are nonresponders to previous therapy, and are even more difficult to treat, underscoring the need for new therapeutic options. Thymalfasin (thymosin-alpha1), in combination with peginterferon-alpha2a, has demonstrated efficacy among difficult-to-treat patients with hepatitis C. The addition of ribavirin to thymalfasin and peginterferon-alpha2a has also exhibited promising results among patients who have genotype 1 hepatitis C, high viral loads and are nonresponders to previous therapy.

Ash SR, Caldwell CA, Singer GG, Lowell JA, Howard TK, Rustgi VK. · Greater Lafayette Health Services, West Lafayette, IN 47906, USA. · Adv Ren Replace Ther. · Pubmed #11927906 No free full text.

Abstract: When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.

Rustgi VK, Esposito S, Hamzeh FM, Shiffman ML. · Liver Transplantation Unit, Georgetown University Medical Center, Washington, DC, USA. · Aliment Pharmacol Ther. · Pubmed #18081737 No free full text.

Abstract: BACKGROUND: Peginterferon alfa-2a/ribavirin treatment resulted in fewer incidences of depression and flu-like symptoms than that of standard interferon/ribavirin, whereas peginterferon alfa-2b/ribavirin and standard interferon/ribavirin treatment resulted in similar incidences of these adverse events (AEs). AIM: To assess the efficacy and safety of peginterferon alfa-2a/ribavirin in genotype 1-infected patients treated for up to 12 weeks with peginterferon alfa-2b/ribavirin but not achieving early virologic response (EVR) (non-EVR) or nontolerant (NT) because of depression, fatigue, flu-like symptoms, or injection-site reactions. METHODS: Nontolerants were treated for an additional 36 weeks and non-EVRs for an additional 60 weeks with peginterferon alfa-2a (180 microg/week)/ribavirin (1000/1200 mg/day). Patients with detectable HCV RNA after 12 weeks were discontinued. RESULTS: Of 25 NTs, 23 (92%) were HCV-RNA negative after 12 weeks on peginterferon alfa-2a/ribavirin and 14 (56%) achieved sustained virologic response. Of 32 non-EVRs to peginterferon alfa-2b/ribavirin, four (13%) achieved EVR with peginterferon alfa-2a/ribavirin and one (3%) achieved sustained virologic response. Four non-EVRs and 0 NTs were withdrawn for AEs; 26 (81%) and 24 (96%), respectively, completed peginterferon alfa-2a/ribavirin treatment or were withdrawn for insufficient response at week 12. In NTs, depression, fatigue, flu-like symptoms, and injection-site reactions declined during treatment. CONCLUSION: Most patients who did not tolerate peginterferon alfa-2b/ribavirin because of AEs, and who completed the full 36-week course of peginterferon alfa-2a/ribavirin treatment, achieved sustained virologic response.

Di Bisceglie AM, Ghalib RH, Hamzeh FM, Rustgi VK. · Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St Louis, MO 63110, USA. · J Viral Hepat. · Pubmed #17875007 No free full text.

Abstract: Patients infected with hepatitis C virus (HCV) genotype 1 and with serum HCV RNA concentrations over 800 000 IU/mL have relatively low rates of virologic response to pegylated interferons. The 2 forms of pegylated interferon have different pharmacokinetic profiles, and pilot studies comparing them have yielded varying results. We compared the virologic response to 12 weeks of treatment with peginterferon alpha-2a plus ribavirin vs peginterferon alpha-2b plus ribavirin in 380 patients who were infected with HCV genotype 1 and had high viral loads. We observed no between-group differences in viral load reduction over time and no differences in the percentage of patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin who achieved early virologic response (EVR), defined as >/=2-log reduction in HCV RNA concentration or undetectable HCV RNA at 12 weeks (66%vs 63%). Serum levels of interferon were more frequently below the level of quantitation in patients treated with peginterferon alpha-2b plus ribavirin (58-68%) than in those treated with peginterferon alpha-2a plus ribavirin (1-2%). Patients treated with peginterferon alpha-2b plus ribavirin had higher rates of discontinuation for safety reasons (6%vs 1%). In conclusion, a substantial percentage of patients infected with HCV genotype 1 and high viral load can achieve EVR when treated with peginterferon and ribavirin. The 2 pegylated interferons showed comparable anti-HCV activity during the first 12 weeks of treatment when combined with the same doses of ribavirin (1000-1200 mg/day), but discontinuations for safety reasons were higher in the patients treated with peginterferon alpha-2b plus ribavirin.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. · Division of Gastroenterology and Hepatology, Medical School of Hannover, Hannover, Germany. · Lancet. · Pubmed #11583749 No free full text.

Abstract: BACKGROUND: A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin. METHODS: 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. FINDINGS: The SVR rate was significantly higher (p=0.01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. INTERPRETATION: In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

Rustgi VK. · Georgetown University Medical Center, 8316 Arlington Blvd., Fairfax, VA 22031, USA. · Curr Med Res Opin. · Pubmed #19275518 No free full text.

Abstract: OBJECTIVE: New treatment options for chronic hepatitis C (CHC) that offer improved efficacy, tolerability, and convenience compared with weekly interferon alfa (IFNalpha)-based regimens are needed. Longer-acting IFNalpha formulations with reduced dosing requirements and improved tolerability have been a focus of drug development efforts. The objective of this report is to review the characteristics, pharmacokinetics, pharmacodynamics, and clinical and virologic outcomes reported in studies of albinterferon alfa-2b (alb-IFN), a novel fusion protein of human albumin and human IFNalpha-2b. METHODS: This review was based on all published data regarding alb-IFN to date. An unlimited PubMed database search was conducted using the keywords 'albuferon,' 'albinterferon,' and 'albumin AND interferon.' RESULTS: Albinterferon alfa-2b has been developed for the treatment of CHC. This agent exhibits a prolonged half-life and duration of antiviral activity that indicate potential suitability for dosing intervals of 2-4 weeks. Phase 2 trials in prior IFN nonresponders and IFN-naïve patients with genotype 1 or 2/3 CHC have shown antiviral activity and acceptable safety/tolerability of alb-IFN 900-1500 microg every 2 weeks and 1200-1500 microg every 4 weeks. Based on the phase 2 data, alb-IFN 900 microg and 1200 microg every 2 weeks were selected for two ongoing phase 3 trials in IFN-naïve patients with genotype 1 and 2/3 CHC. CONCLUSIONS: Albinterferon alfa-2b exhibits high antiviral activity, and appears to offer safety/tolerability comparable to the current standard of care, and health-related quality-of-life benefits in patients with CHC. Its ability to maintain drug concentrations above the 90% effective concentration over prolonged dosing intervals suggests that it may be an ideal partner for combination therapy with direct antiviral agents in CHC. The results of the phase 3 trials are eagerly anticipated as they should greatly clarify the future role of alb-IFN in the treatment of CHC.

Sherman M, Yurdaydin C, Simsek H, Silva M, Liaw YF, Rustgi VK, Sette H, Tsai N, Tenney DJ, Vaughan J, Kreter B, Hindes R, Anonymous00005. · Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada. · Hepatology. · Pubmed #18537189 No free full text.

Abstract: In hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization. We assessed the efficacy, safety, and resistance profile of entecavir through 96 weeks of treatment. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir-treated patients who had a protocol-defined virologic response (HBV branched DNA [bDNA] < 0.7 MEq/mL but HBeAg-positive) continued blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety, and emerging resistance. Cumulative proportions of all treated patients who achieved confirmed efficacy endpoints were also analyzed. Between week 48 and the end of dosing, the proportions of patients with HBV DNA <300 copies/mL by polymerase chain reaction increased from 21% to 40%, and alanine aminotransferase normalization (< or =1x upper limit of normal) increased from 65% to 81%. In the second year, HBeAg seroconversion was achieved by 10% of patients. Of the 77 patients in the second year treatment cohort, entecavir resistance emerged in six patients, and seven experienced virologic breakthrough (five with genotypic resistance acquired before year 2). The safety profile of entecavir in the second year of therapy was consistent with that reported during year 1. CONCLUSION: Through 96 weeks of treatment, 1 mg entecavir resulted in continued clinical benefit in lamivudine-refractory HBeAg-positive chronic hepatitis B patients with a safety profile comparable to lamivudine.

Rustgi VK. · Department of Medicine and Surgery, Georgetown University Medical Center, 8316 Arlington Blvd., Ste 515, Fairfax, VA 22031, USA. · Ann N Y Acad Sci. · Pubmed #17600289 No free full text.

Abstract: The purpose of this review article is to examine previous and ongoing studies of thymalfasin in combination with peginterferon-alpha2a and peginterferon-alpha2a plus ribavirin in difficult-to-treat hepatitis C virus (HCV) patients. The following studies will be reviewed in detail: (1) Sherman and colleagues conducted a study in 109 HCV RNA positive HVC patients comparing the combination of thymalfasin + IFN versus IFN alone versus placebo. (2) Rustgi et al. evaluated the efficacy and safety of thymalfasin and peg-IFN-alpha2a in 31 genotype 1, high viral load, HCV nonresponders in a 12-week viral kinetic study. (3) Di Bisceglie, Sherman et al. performed a study of previous HCV nonresponders being retreated with either peginterferon-alpha2a plus thymalfasin or peginterferon-alpha2a plus placebo. (4) Poo and colleagues in Mexico evaluated triple combination therapy using thymalfasin, peginterferon-alpha2a, and ribavirin for the treatment of Hispanic HCV nonresponders.

Marroquin CE, Marino G, Kuo PC, Plotkin JS, Rustgi VK, Lu AD, Edwards E, Taranto S, Johnson LB. · Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Georgetown University Medical Center, Washington, DC 20007-2197, USA. · Liver Transpl. · Pubmed #11552208 links to  free full text

Abstract: A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus-positive (HCV(+)) donor livers for HCV(+) recipients. This study reviews the clinical outcome of a large series of HCV(+) recipients of HCV(+) liver allografts and compares their course with that of HCV(+) recipients of HCV-negative (HCV(-)) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV(+) transplant recipients were analyzed. Two groups were identified: a group of HCV(+) recipients of HCV(+) donor livers (n = 96), and a group of HCV(+) recipients of HCV(-) donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV(+) allograft (8.3% v 3.1%; P =.01). Patient survival showed a significant difference for the HCV(+) group compared with the HCV(-) group (90% v 77%; P =.01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV(+) group and only 1.3% in the HCV(-) group (P =.04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV(+) recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV(+) donor livers for transplantation in HCV(+) recipients safely and effectively expands the organ donor pool.

Gaweco AS, Wiesner RH, Porayko M, Rustgi VK, Yong S, Hamdani R, Harig J, Chejfec G, McClatchey KD, Van Thiel DH. · Liver Transplant Program, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA. · Hepatology. · Pubmed #10796896 No free full text.

Abstract: Nuclear factor kappaB (NF-kappaB) is activated during viral infection and is central to the regulation of host immune responses. The NF-kappaB activation status and its morphological sources were assessed by immunohistochemistry in allograft biopsy specimens of orthotopic liver transplantation patients with recurrent hepatitis C virus (HCV). Hepatocellular NF-kappaB immunostaining was detected in HCV cases compared with controls (nontransplant: P <.001; transplant: P =.006), which correlated with the number of NF-kappaB positive hepatocytes (P =.007) and contrasted to the absent to weak staining of controls (nontransplant: P =.001; transplant: P =.009). Enhanced NF-kappaB staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-kappaB immunoreactivity was detected in CD68-positive Kupffer cells and macrophages of all HCV specimens compared with a few controls (nontransplant: P <.001; transplant: P =.001) and contrasted to the weak staining of controls (nontransplant: P <.001; transplant: P =.001). NF-kappaB-positive immunoreactivity correlated with the number of T cell receptor (TCR) alpha/beta-positive lymphocytes (P <.001), which was not observed in controls. In those HCV cases showing evidence of necroinflammatory activity (grade) and individual features of portal inflammation, periportal inflammation/piecemeal necrosis, lobular inflammation, and fibrosis (stage), higher NF-kappaB staining intensity scores within bile ducts, proliferating ductules, hepatocytes (piecemeal necrosis: P =.016; stage: P =.030), and lymphocytes (stage: P =.044) and increased number of NF-kappaB-positive cells within bile ducts, proliferating ductules (grade, lobular inflammation, piecemeal necrosis, stage: P =.022), hepatocytes, and lymphocytes were observed. Increased staining intensity and frequency of NF-kappaB-positive cells were similarly observed in HCV-positive allografts obtained from patients under tacrolimus- compared with cyclosporine-based immunosuppression. These data implicate an immunoregulatory role of intragraft NF-kappaB activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.