Hepatitis: Rossi S

Hashemi N, Rossi S, Navarro VJ, Herrine SK. · Thomas Jefferson University, Division of Gastroenterology and Hepatology, Philadelphia, PA, USA. · Expert Opin Drug Saf. · Pubmed #18983223 No free full text.

Abstract: BACKGROUND: Combination of 'pegylated' interferons (IFNs) plus ribavirin, the standard treatment of chronic hepatitis C (CHC), is frequently associated with side effects. Anticipation, recognition and proper management of these side effects are important to ensure compliance with therapy and achievement of sustained virologic response. OBJECTIVE: To illustrate the side effect profile of pegIFN-alpha in the treatment of CHC. METHODS: Studies and abstracts were identified through a computerized, English language literature search. Key search terms included peginterferon and CHC. Information available only in abstract form was retrieved from national and international hepatology associations. RESULTS: Most adverse events occurring with combination therapy can be anticipated and managed appropriately; therefore, premature discontinuation of therapy owing to side effects is not required in most patients.

Herrine SK, Rossi S, Navarro VJ. · Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, USA. · Clin Exp Med. · Pubmed #16550340 No free full text.

Abstract: Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality throughout the world. Although reliable figures regarding the global prevalence of HCV infection are wanting, it is likely that HCV prevalence will continue to increase. Injection drug use is the most important source of HCV transmission in the developed world, while unsafe therapeutic injection is an important source of transmission in developing nations. The majority of exposed individuals become chronically infected, of whom 50% develop chronic liver injury. Cirrhosis and hepatocellular carcinoma can arise in those chronically infected over a mean of 20-30 years. Despite this high prevalence and morbidity, recommendations regarding who to screen by antibody testing remain disparate. Quantitative measurement of HCV RNA and HCV genotyping is useful in predicting response to antiviral therapy. Noninvasive methods of detecting liver injury, such as serologic batteries, have not been as informative or predictable as liver biopsy. The current pharmacologic standard of care for chronic HCV infection is the combination of subcutaneous peginterferon and oral ribavirin, which yields sustained virologic response in 54%-56%. Higher rates of SVR are seen in those patients who are infected with HCV genotypes 2 and 3. As intravenous drug use remains the most important source of HCV transmission in the US and Europe, education within this group is an important preventive tool.

Puoti M, Zanini B, Bruno R, Airoldi M, Rossi S, Quiros Roldan E, El Hamad I, Moretti F, Castelli F, Sacchi P, Filice G, Carosi G. · Clinica di Malattie Infettive e Tropicali Università degli Studi di Brescia - AO Spedali Civili, Brescia, Italy. · HIV Clin Trials. · Pubmed #12187507 links to  free full text

Abstract: Human immunodeficiency virus (HIV) co-infection accelerates progression of hepatitis C virus (HCV) toward cirrhosis. Thus, with the increase of life expectancy observed after introduction of combination antiretroviral treatment, liver disease is becoming an increasing cause of morbidity and mortality in HIV-infected patients. In addition, HCV co-infection blunts CD4 restoration induced by HAART and increases HAART hepatotoxicity. For all these reasons, anti-HCV treatment is mandatory in HIV seropositives. The perfect treatment of hepatitis C should not only be safe and effective, but it should not have any adverse impact on HIV diseases and concurrent anti-HIV therapy. Two drugs are currently licensed for treatment of HCV: interferon alfa (IFNalpha) and ribavirin. Three hundred and thirty-eight patients have been included in pilot studies on the efficacy and tolerability of IFNalpha monotherapy: 16% showed sustained response and 10% dropped out. No significant adverse impact of IFNalpha monotherapy on HIV diseases or antiretroviral treatment has been observed. IFNalpha and ribavirin in combination have been introduced more recently: only 88 patients were included in pilot studies published as full papers with a 25% sustained response and an 11% rate of drop outs. Anemia and cumulative toxicity with didanosine were the most important side effects of combination treatment, but it did not affect HIV disease progression. Higher rates of sustained response (33%) without increase of side effects have been observed in preliminary experiences with the new long-acting pegylated interferons in combination with ribavirin. The search for the perfect treatment continues.

Bruno S, Maisonneuve P, Castellana P, Rotmensz N, Rossi S, Maggioni M, Persico M, Colombo A, Monasterolo F, Casadei-Giunchi D, Desiderio F, Stroffolini T, Sacchini V, Decensi A, Veronesi U. · Liver Unit, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Corso di Porta Nuova 23, 20121 Milan, Italy. · BMJ. · Pubmed #15746106 links to  free full text

Abstract: OBJECTIVE: To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SETTING AND PARTICIPANTS: 5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy. INTERVENTION: Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years. MAIN OUTCOME MEASURE: Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (> or = 1.5 times upper limit of normal) over a six month period. RESULTS: During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)--hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (1 tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years. CONCLUSIONS: Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow up seems to be indolent.

Sulkowski M, Wright T, Rossi S, Arora S, Lamb M, Wang K, Gries JM, Yalamanchili S. · Viral Hepatitis Center, Johns Hopkins Medical Institutions, 1830 E Monument St, Room 448, Baltimore, MD 21205, USA. · Clin Pharmacol Ther. · Pubmed #15735615 No free full text.

Abstract: OBJECTIVE: Our objective was to quantify the pharmacokinetics of methadone and the pharmacokinetics and pharmacodynamics of peginterferon alfa-2a (40 kd) in patients with chronic hepatitis C undergoing methadone maintenance therapy. METHODS: Adults with chronic hepatitis C who had been receiving a consistent methadone maintenance regimen for at least 3 months were eligible for this open-label, multicenter, nonrandomized drug interaction study. All patients received 180 microg subcutaneous peginterferon alfa-2a once weekly for 4 weeks and continued their methadone regimen. Serial blood samples were collected at baseline and immediately before and for up to 168 hours after study drug administration for the purposes of quantifying methadone and peginterferon alfa-2a serum concentrations, measuring serum 2',5'-oligoadenylate synthetase activity, and determining hepatitis C virus ribonucleic acid levels. RESULTS: Twenty-four patients were enrolled. Methadone exposure, as measured by maximum serum concentration (C(max)) and area under the concentration-time curve (AUC) normalized to a 100-mg/d dose, after 4 doses of peginterferon alfa-2a increased by 10% to 15% when compared with baseline. The week 4/baseline ratio of the mean C(max) was 1.11 (90% confidence interval [CI], 1.02-1.22), and for AUC from time 0 to 24 hours, the week 4/baseline ratio was 1.15 (90% CI, 1.08-1.23). The mean accumulation ratios (week 4/first dose) for C(max) and AUC from time 0 to 168 hours of peginterferon alfa-2a were 2.1 and 2.3, respectively. CONCLUSIONS: Peginterferon alfa-2a does not appreciably alter the pharmacokinetics of methadone.

Aora S, Xu C, Teng A, Peterson J, Yeh LT, Gish R, Lau D, Rossi S, Lin CC. · Valeant Pharmaceuticals International, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. · J Clin Pharmacol. · Pubmed #15703363 No free full text.

Abstract: The current study was carried out to evaluate pharmacokinetic profiles of viramidine and ribavirin in patients (n = 8 per dose group) with compensated hepatitis C infection following oral dosing of viramidine (400, 600, or 800 mg bid for 4 weeks). Pharmacokinetic parameters were determined on days 1 and 29 based on plasma, red blood cell, and urine concentrations of viramidine and ribavirin. The results indicate rapid absorption and conversion of viramidine to ribavirin after oral administration of viramidine. Viramidine and ribavirin exposure in plasma and RBCs generally increased from the 400- to 600-mg dose level of viramidine. However, no further increase in exposure was noted at the 800-mg dose. Long half-lives for viramidine (66-76 hours in plasma and 200-420 hours in red blood cells) and ribavirin (340-410 hours in plasma and 360-430 hours in red blood cells) were noted. A negligible amount of viramidine (1%-4% of dose) and a small amount of ribavirin (9%-14% of dose) were excreted in the urine. The renal clearance was low for both viramidine (5-8 L/h) and ribavirin (4-7 L/h). Significant accumulation of viramidine was noted in red blood cells (accumulation factor [R] = 5-8) but not in plasma (R = 2). Extensive accumulation of ribavirin was noted in both plasma (R = 9-17) and red blood cells (R = 77-129). Steady-state levels of ribavirin and viramidine in plasma and red blood cells were achieved by day 22. At steady state, there was extensive conversion of viramidine to ribavirin in both plasma and red blood cells. Both viramidine and ribavirin were preferentially distributed into red blood cells than plasma.

Puoti M, Cadeo GP, Putzolu V, Forleo MA, Barni MC, Cristini G, Rossi S, Spinetti A, Zaltron S, Zanini B, Quiros-Roldan E, Paraninfo G, Gargiulo F, Carosi G. · Clinic for Infectious and Tropical Diseases, Brescia Hospital, Italy. · Dig Liver Dis. · Pubmed #11346146 No free full text.

Abstract: BACKGROUND: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal. AIMS: To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy. PATIENTS: Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)]. RESULTS: A sustained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response. CONCLUSIONS: These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.

Magalini A, Puoti M, Putzolu V, Quiros-Roldan E, Forleo MA, Rossi S, Zaltron S, Spinetti A, Zanini B, Zonaro A, Solfrini R, Carosi G. · Department of Clinical Chemistry, O.P. Richiedei, Brescia, Italy. · J Clin Lab Anal. · Pubmed #10797610 No free full text.

Abstract: Early monitoring of HCVRNA during interferon treatment may allow clinicians to obtain important information that could help them to adopt therapeutic decisions in individual cases. The hepatitis C virus infection is highly dynamic and a daily high dose of IFN may induce a decline of viremia of 95+/-10% of baseline value after 24 to 48 hours of treatment. The importance of this early antiviral efficacy has not been understood. We have measured HCVRNA levels in 47 patients with chronic hepatitis C infection during interferon treatment to study HCVRNA kinetics and evaluate the predictive value of the early decay of viremia on the virological response after one month of treatment. Sixty percent of treated patients showed early virological response (EVR) and it was significantly associated with low HCVRNA levels and a genotype other than 1b. Finally, the absence of an 85% decline in HCVRNA levels after 3 days of treatment observed in 11 out of 45 patients (24%) was an absolute and very early predictor of the absence of EVR in the study population.

Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A, Silini EM, Almasio PL, Maisonneuve P. · Department of Internal Medicine, AO Fatebenefratelli e Oftalmico, Milan, Italy. · Am J Gastroenterol. · Pubmed #19352340 No free full text.

Abstract: OBJECTIVES: The identification of prognostic factors associated with mortality is crucial in any clinical setting. METHODS: We enrolled in a prospective study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis, consecutively observed between 1989 and 1992. At entry, patients underwent upper endoscopy to detect esophageal varices, and were then surveilled by serial clinical and ultrasonographic examination. The model for end-stage liver disease (MELD) score was calculated with information collected at enrollment. Baseline predictors and intercurrent events associated with mortality were assessed using the Cox regression model. RESULTS: During a median follow-up of 14.4 years, 194 subjects received a single course of interferon monotherapy, 131 patients developed decompensation (ascites, bleeding, hepatic encephalopathy), 109 patients had hepatocellular carcinoma (HCC), 9 had liver transplant, and 158 died. Esophageal varices were associated with development of decompensation (hazard ratio (HR), 2.09; 95% confidence interval (CI), 1.33-3.30) and liver-related death (HR, 2.27; 95% CI, 1.41-3.66). A MELD score of > 10 predicted overall mortality (HR, 2.15; 95% CI, 1.50-3.09). Overall survival of patients with MELD < or = 10 was 80% at 10 years. HCC occurrence increased the risk of decompensation fivefold (HR, 5.52; 95% CI, 3.77-8.09). Hepatic and overall mortality hazard ratios were 8.62 (95% CI, 5.57-13.3) and 3.80 (95% CI, 2.67-5.42), respectively, for patients who developed HCC, and 16.9 (95% CI, 9.97-28.6) and 7.08 (95% CI, 4.88-10.2) for those who experienced decompensation. CONCLUSIONS: In patients with compensated HCV-induced cirrhosis, the presence of esophageal varices at baseline predicted decompensation and mortality. The development of HCC during follow-up strongly hastens the occurrence of decompensation, which is the main determinant of death. Patients with a MELD score < or = 10 at study entry had a prolonged life expectancy.

Gentile C, Alberini I, Manini I, Rossi S, Montomoli E, Pozzi T, Rizzo C, Alfonsi V. · University of Siena, Department of Physiopathology, Experimental Medicine and Public Health, Tuscany, Italy. · Euro Surveill. · Pubmed #19317984 links to  free full text

Abstract: Information regarding the current seroprevalence of hepatitis A virus (HAV) is useful for the control of HAV infections. The objective of our study was to evaluate the prevalence of anti-HAV antibodies among children (1-5 years old) and young adults (15-20 years old) in Tuscany, in central Italy. A total of 565 sera were collected in three years 1992, 1998 and 2004, equally distributed between the two age groups. The overal proportion of those that tested positive for anti-HAV antibodies was 8.3%. The proportion of immune children (1-5 years old) statistically significantly increased over the years. The percentage of immune subjects among 15-20-year-old young adults varied over the years, not showing a significant statistical trend, nevertheless our findings indicate that in a low endemicity area, adolescents and young adults are becoming increasingly susceptible to HAV infection. On-going monitoring of immunity to HAV is necessary for detecting trends over time.

Dhillon R, Rossi S, Herrine SK. · Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA. · Ther Clin Risk Manag. · Pubmed #19209261 links to  free full text

Abstract: Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA level, and presence of rapid virologic response (RVR) and early virologic response (EVR). Use of weight-based ribavirin dosing appears to be safe and enhances the likelihood of sustained virologic response (SVR). Adverse effects most commonly encountered are anemia and weight loss. Mitochondrial toxicity can occur in the setting of concomitant nucleoside reverse transcriptase inhibitor use, especially didanosine, abacavir, and zidovudine, and these should be discontinued before initiation of ribavirin therapy. Discontinuation of therapy should be considered in patients failing to demonstrate EVR, though ongoing trials are investigating a potential role for maintenance therapy in these patients. Peginterferon combined with weight-based ribavirin is appropriate and safe for treatment of HCV in HIV - HCV coinfected patients. This review summarizes the data supporting these recommendations.

Mehendiratta V, Mitroo P, Bombonati A, Navarro VJ, Rossi S, Rubin R, Herrine SK. · Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, USA. · Clin Gastroenterol Hepatol. · Pubmed #18955163 No free full text.

Abstract: BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is characterized by the presence of circulating autoantibodies, hypergammaglobulinemia, necroinflammatory histology, and a response to immunosuppressive drugs. The goal of this retrospective study was to determine whether the presence of antinuclear antibodies (ANAs) or anti-smooth muscle antibodies (ASMAs) in patients with AIH correlated with clinical presentation, histologic findings, or response to immunosuppressive therapy. METHODS: Fifty-two patients diagnosed with AIH, on the basis of the revised scoring system of International Autoimmune Hepatitis group, were reviewed. Data on age, gender, aminotransferase levels, autoantibody titers, treatment regimens, and response to treatment were recorded. Seropositivity was defined as ANA >1:40 or ASMA >1:40. Percutaneous liver biopsies obtained at the initial presentation were reviewed. RESULTS: Forty-two patients with AIH (81%) were seropositive, and 10 (19%) were seronegative. Both groups were similar with respect to demographics, treatment regimens, and response to therapy. Histologic parameters were similar among the 2 groups, including portal and lobular inflammation, piecemeal necrosis, and centrilobular necrosis. There were no significant differences in aminotransferase levels at diagnosis or after treatment. CONCLUSIONS: The prevalence of ANAs or ASMAs did not correlate with the clinical or histologic severity of AIH at diagnosis. Furthermore, there was no correlation between antibody status and response to immunosuppressive therapy. Therefore, patients who meet the diagnosis of AIH on the basis of the revised scoring system of International Autoimmune Hepatitis Group should be given immunosuppressive therapy, regardless of antibody status.

Rossi S, Assis DN, Awsare M, Brunner M, Skole K, Rai J, Andrel J, Herrine SK, Reddy RK, Navarro VJ. · Thomas Jefferson University Hospital and Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Drug Saf. · Pubmed #18302450 No free full text.

Abstract: BACKGROUND: Over-the-counter analgesics (OTCAs), principally paracetamol (acetaminophen)-containing compounds and NSAIDs, are commonly used medications. Guidelines for the use of these agents in patients with chronic liver disease (CLD) are not available, despite the possibility that such patients may be more susceptible to the effects of an adverse reaction. Notwithstanding the lack of guidelines for healthcare providers, patients are often counselled to modify their use of these drugs. Therefore, the primary aim of this study was to assess healthcare providers' recommendations on how OTCAs should be used by patients with CLD. METHODS: An 11-question web-based survey was distributed via email to healthcare providers participating in four healthcare networks in the US, to determine what recommendations they make to patients with cirrhosis (compensated and decompensated) and chronic hepatitis regarding the use of paracetamol and NSAIDs. Healthcare providers were also queried about the recommendations they make to patients with cirrhosis regarding pain control, and on the use of paracetamol for patients who consume alcohol daily. RESULTS: Overall, a 12% response rate was obtained. Internal medicine, family practice, paediatrics, and gastroenterology were the most represented practice types. Recommendations against the use of NSAIDs were significantly less common than recommendations against paracetamol use, in cases of both compensated and decompensated cirrhosis (p = 0.001). Non-gastroenterologists and non-primary care physicians were the least likely to recommend against NSAID use (p = 0.001), while gastroenterologists were the least likely to recommend against paracetamol in these patients (p = 0.001). It was the recommendation of most respondents that OTCAs should be avoided in patients with cirrhosis, and that paracetamol should be avoided or its dose reduced in the setting of daily alcohol use. CONCLUSIONS: Significant variability exists among healthcare providers on their recommendations for OTCA use in the setting of chronic liver disease. Non-gastroenterologists are more likely to recommend against the use of paracetamol than NSAIDs, and patients with chronic liver disease may be under-treated for pain.

Jakab SS, Navarro VJ, Colombe BW, Daskalakis C, Herrine SK, Rossi S. · Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University, and Department of Tissue Typing, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. · Liver Transpl. · Pubmed #17902126 links to  free full text

Abstract: Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. · Liver Unit, Department of Medicine, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Milan, Italy. · Hepatology. · Pubmed #17680653 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the most frequent cause of death in patients with hepatitis C virus (HCV)-induced cirrhosis. Despite a number of studies in different populations worldwide suggesting an association between HCV genotype 1 and the risk of HCC, no consensus has emerged yet on this matter, which is still controversial. In an attempt to clarify this issue, a prospective study of 163 consecutive HCV-positive patients with cirrhosis, who were enrolled between January 1989 and December 1990, was carried out. HCC occurrence was detected by ultrasound surveillance every 6 months. Independent predictors of HCC were assessed with a Cox regression analysis. After a median follow-up of 10.7 years, 44 [4.26/100/year, confidence interval (CI) = 3.11-5.68/100/year] of 104 patients infected with genotype 1b developed HCC versus 10 (1.69/100/year, CI = 0.82-3.09/100/year) of 52 patients infected with genotype 2a/c (P = 0.0001). Multivariate analysis showed that HCV genotype 1b was independently associated with HCC development [hazard ratio (HR) = 3.02, 95% CI = 1.40-6.53]. Other predictors of HCC were esophageal varices (HR = 2.15, 95% CI = 1.03-4.47), male gender (HR = 2.12, 95% CI = 1.10-4.11), and age over 60 years (HR = 5.96, 95% CI = 1.23-28.8). Conclusion: HCV genotype 1b is associated with a statistically significant higher risk of developing HCC. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia.

Trooskin SB, Navarro VJ, Winn RJ, Axelrod DJ, McNeal AS, Velez M, Herrine SK, Rossi S. · Division of Gastroenterology and Hepatology, Thomas Jefferson University, Suite 480 Main Building, Philadelphia, PA 19107, USA. · World J Gastroenterol. · Pubmed #17373742 links to  free full text

Abstract: AIM: To determine rates of hepatitis C (HCV) risk factor ascertainment, testing, and referral in urban primary care practices, with particular attention to the effect of race and ethnicity. METHODS: Retrospective chart review from four primary care sites in Philadelphia; two academic primary care practices and two community clinics was performed. Demographics, HCV risk factors, and other risk exposure information were collected. RESULTS: Four thousand four hundred and seven charts were reviewed. Providers documented histories of injection drug use (IDU) and transfusion for less than 20% and 5% of patients, respectively. Only 55% of patients who admitted IDU were tested for HCV. Overall, minorities were more likely to have information regarding a risk factor documented than their white counterparts (79% vs 68%, P < 0.0001). Hispanics were less likely to have a risk factor history documented, compared to blacks and whites (P < 0.0001). Overall, minorities were less likely to be tested for HCV than whites in the presence of a known risk factor (23% vs 35%, P = 0.004). Among patients without documentation of risk factors, blacks and Hispanics were more likely to be tested than whites (20% and 24%, vs 13%, P < 0.005, respectively). CONCLUSION: (1) Documentation of an HCV risk factor history in urban primary care is uncommon, (2) Racial differences exist with respect to HCV risk factor ascertainment and testing, (3) Minority patients, positive for HCV, are less likely to be referred for subspecialty care and treatment. Overall, minorities are less likely to be tested for HCV than whites in the presence of a known risk factor.

Bini EJ, Bräu N, Currie S, Shen H, Anand BS, Hu KQ, Jeffers L, Ho SB, Johnson D, Schmidt WN, King P, Cheung R, Morgan TR, Awad J, Pedrosa M, Chang KM, Aytaman A, Simon F, Hagedorn C, Moseley R, Ahmad J, Mendenhall C, Waters B, Strader D, Sasaki AW, Rossi S, Wright TL. · VA New York Harbor Healthcare System and NYU School of Medicine, New York, New York 10010, USA. · Am J Gastroenterol. · Pubmed #16086714 No free full text.

Abstract: BACKGROUND: Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment. METHODS: We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician. RESULTS: Overall, 32.2% (95% CI, 30.8-33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2-42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24-25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85-13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70-13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42-16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0-78.3%) agreed to be treated and multivariable analysis showed that persons >/=50 yr of age (OR = 1.37; 95% CI, 1.07-1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08-1.93) were more likely to decline treatment. CONCLUSIONS: The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

Puoti M, Babudieri S, Rezza G, Viale P, Antonini MG, Maida I, Rossi S, Zanini B, Putzolu V, Fenu L, Baiguera C, Sassu S, Carosi G, Mura MS. · Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. · Antivir Ther. · Pubmed #15456094 No free full text.

Abstract: Standard interferon treatment is known to increase the risk of infections; this risk also needs to be evaluated in clinical practice for pegylated interferon. To this end, we studied 255 patients treated with standard (103) or pegylated (152) interferon, in combination with ribavirin, for hepatitis C. Overall, 31 anti-hepatitis C virus treatment-related infections were observed. Neutropenia (neutrophil counts below 1x10(3) cells/ml) was observed in a significantly higher proportion of patients treated with pegylated interferons (48% vs 9%; P=0.0009). Of the 31 infections, eight were respiratory infections and were observed only in patients with neutropenia. None of the non-respiratory infections was observed in patients with neutropenia. Multivariate analysis, using Cox's proportional hazards regression model, found a higher risk of all infections associated with both use of pegylated interferons [hazard ratio (HR) 4.6] and neutropenia (HR 2.46). However, neutropenia was independently associated with acute respiratory infections only and use of pegylated interferons with non-respiratory infections. In summary, use of pegylated interferon appears to increase the risk of non-respiratory infections independently from neutropenia.

Herrine SK, Michael B, Ma WL, Rossi S, Dunn SR, Hyslop T. · Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Am J Gastroenterol. · Pubmed #12385449 No free full text.

Abstract: OBJECTIVE: The prevalence of hepatitis C virus (HCV) in patients on chronic hemodialysis (HD) is near 9%. Transaminases, which are lower in HD patients, are not effective in screening for HCV. Our aim was to design an HCV risk stratification strategy incorporating lowered aminotransferase levels and other clinical parameters. METHODS: Patient serum from 168 consecutive HD patients was analyzed for AST, ALT, ferritin, and hepatitis C antibody. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for lower transaminase values. Multivariate classification and regression tree analysis was used to determine the best combination of variables to predict risk for HCV infection. RESULTS: Median AST and ALT levels were higher in anti-HCV Ab(+) patients (p < 0.05). Applying a lower cutoff value for ALT of 16 IU/L resulted in a sensitivity of 61.1%, a specificity of 66.7%, a positive predictive value of 33.9%, and a negative predictive value of 86.0% for detection of HCV infection. Multivariate classification and regression tree analysis derived an algorithm using patient age, months on HD, and AST, resulting in a 97.2% sensitivity and a 51.9% specificity for the detection of HCV(+) HD patients. CONCLUSIONS: A lower normal cutoff value of 18 IU/L for AST and 16 IU/L for ALT increased sensitivity and specificity for the detection of HCV infection in HD patients. An algorithm combining lower transaminases with clinical parameters improved both sensitivity and specificity in HCV detection. Prospective confirmation of this algorithm would allow more selective HCV enzyme immunoassay and polymerase chain reaction testing in dialysis units.

Rossi S, De Filippi F, Saibeni S, Persico M, Bollani S, Camera A, Rizzolo L, Maria Croce A, Bruno S. · No affiliation provided · Am J Gastroenterol. · Pubmed #17958768 No free full text.

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