Hepatitis: Navarro VJ

Kearney KR, Thornton JJ, Navarro VJ. · Lankenau Hospital, Department of Gastroenterology, 100 Lancaster Avenue, Wynnewood, PA 19096, USA. · Expert Opin Pharmacother. · Pubmed #19040344 No free full text.

Abstract: BACKGROUND: The current standard therapy for chronic hepatitis C virus (HCV), combination therapy with pegylated interferon and ribavirin, is plagued by a number of side effects, most notably anemia. This anemia is typically managed with a reduction of ribavirin dosing, which may lead to reduced efficacy. Taribavirin, an oral prodrug of ribavirin, which has been shown to induce a lesser degree of anemia, is being investigated for the treatment of chronic HCV. OBJECTIVE: To summarize the clinical trials involving taribavirin and its potential role in the treatment of chronic HCV. METHODS: Information was obtained via searches for data related to taribavirin, as well as other current and investigational therapies for chronic HCV. Press releases discussing otherwise unpublished trial outcomes were obtained from the website of Valeant Pharmaceuticals, the producer of Viramidine (taribavirin). CONCLUSION: Taribavirin may increase adherence to therapy for chronic HCV by reducing the need for dose reduction due to anemia. A recent Phase II trial investigating early and sustained virological response showed no statistically significant differences between ribavirin 1000/1200 mg and taribavirin at 800-, 1200-, or 1600-mg dosing, while illustrating a lesser degree of anemia in 800- and 1200-mg dosing of taribavirin. Ongoing studies will continue to examine the efficacy of combination therapy with taribavirin in the place of ribavirin.

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.

Halegoua-De Marzio D, Navarro VJ. · Department of Medicine, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107, USA. · Curr Opin Drug Discov Devel. · Pubmed #18175267 No free full text.

Abstract: A contemporary understanding of the clinical aspects of drug-induced liver injury (DILI) is paramount for timely diagnosis and appropriate management. An accurate diagnosis of DILI is based upon a combination of appropriate history, clinical presentation, biochemical tests and the exclusion of other causes of liver injury. In clinical drug development, elevations in levels of alanine aminotransferase of up to five-fold the upper limit of normal are tolerated; however, the occurrence of hepatocellular jaundice may jeopardize a development program. At the very least, such an occurrence should trigger an extremely careful reassessment of the risk/benefit ratio of a drug. New methods to predict and detect DILI are currently being aggressively investigated.

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.

Navarro VJ, Senior JR. · Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Philadelphia, USA. · N Engl J Med. · Pubmed #16481640 No free full text.

This publication has no abstract.

Addesa JA, Navarro VJ. · Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208019, New Haven, CT 06520-8019, USA. · Compr Ther. · Pubmed #11765685 No free full text.

Abstract: Hepatitis C is the most common blood-borne infection in the US affecting at least 2.7 million Americans today. The majority of infected patients remain asymptomatic until the end-stages of the disease, making the infection difficult to identify, study, and treat.

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.

Durante AJ, Meek JI, St Louis T, Navarro VJ, Sofair AN. · Yale Center for Public Health, New Haven, CT 06510, USA. · Conn Med. · Pubmed #18763666 No free full text.

Abstract: Chronic viral hepatitis can cause cirrhosis. Viral hepatitis-related cirrhosis may be causing an increasing health burden since exposure to hepatitis B virus and hepatitis C virus in the United States increased starting in the 1960s. Using hospital discharge data, we estimated the number of adult New Haven County residents hospitalized for cirrhosis and examined the proportion caused by chronic viral hepatitis. Data on etiology were obtained from hospital discharge records, death certificate information, and New Haven County Liver Study records. From 1 October 1999 to 30 September 2000, 269 adult New Haven County residents were hospitalized for cirrhosis in a New Haven County hospital, for an incidence of 43.2 per 100,000 population. The burden of viral hepatitis-related cirrhosis was 15.9 per 100,000. Hepatitis C virus was the most common viral etiology. Given the long period between initial infection and clinical decompensation, screening and treatment programs aimed at reducing viral hepatitis-related morbidity should reduce hospitalization rates.

Durante AJ, St Louis T, Meek JI, Navarro VJ, Sofair AN. · Yale Center for Public Health, New Haven, CT 06510, USA. · Conn Med. · Pubmed #18763665 No free full text.

Abstract: PURPOSE: The United States National Center for Health Statistics (NCHS) uses death certificate data to estimate the burden of serious disease. This study aimed to determine the accuracy of the NCHS method for estimating the burden of chronic liver disease (CLD). METHOD: The authors identified death certificates of New Haven County residents who died from October 1999-September 2000 that were assigned one of 115 ICD-10 codes that might indicate CLD. They reviewed medical charts, medical examiner records and a certifier questionnaire to determine whether CLD was the cause of death. RESULT: Using the authors' determination of CLD status as the gold standard, the specificity of the NCHS classification was high (86%), but the sensitivity was low (36%). The authors found that adding selected ICD-10 codes to those considered by the NCHS to be CLD (certain CLD malignancies and viral hepatitis) could improve sensitivity. Ensuring that deaths attributed by certifiers to "End Stage Liver Disease" were coded as CLD could also improve completeness. These modifications could increase sensitivity substantially with little effect on specificity. CONCLUSION: The NCHS method may understate the CLD burden substantially which could have a detrimental effect on planning for and evaluating prevention and treatment. Modifications could improve completeness.

Bell BP, Manos MM, Zaman A, Terrault N, Thomas A, Navarro VJ, Dhotre KB, Murphy RC, Van Ness GR, Stabach N, Robert ME, Bower WA, Bialek SR, Sofair AN. · Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, Sexually Transmitted Diseases and Tuberculosis Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. · Am J Gastroenterol. · Pubmed #18684170 No free full text.

Abstract: OBJECTIVES: Chronic liver disease (CLD) is an important cause of morbidity and mortality, but the epidemiology is not well described. We conducted prospective population-based surveillance to estimate newly diagnosed CLD incidence, characterize etiology distribution, and determine disease stage. METHODS: We identified cases of CLD newly diagnosed during 1999-2001 among adult county residents seen in any gastroenterology practice in New Haven County, Connecticut; Multnomah County, Oregon; and Northern California Kaiser Permanente Medical Care Program (KPMCP, Oakland, California [total population 1.48 million]). We defined CLD as abnormal liver tests of at least 6 months' duration or pathologic, clinical, or radiologic evidence of CLD. Consenting patients were interviewed, a blood specimen obtained, and the medical record reviewed. RESULTS: We identified 2,353 patients with newly diagnosed CLD (63.9 cases/100,000 population), including 1,225 hepatitis C patients (33.2 cases/100,000). Men aged 45-54 yr had the highest hepatitis C incidence rate (111.3/100,000). Among 1,040 enrolled patients, the median age was 48 yr (range 19-86 yr). Hepatitis C, either alone (442 [42%]) or in combination with alcohol-related liver disease (ALD) (228 [22%]), accounted for two-thirds of the cases. Other etiologies included nonalcoholic fatty liver disease (NAFLD, 95 [9%]), ALD (82 [8%]), and hepatitis B (36 [3%]). Other identified etiologies each accounted for <3% of the cases. A total of 184 patients (18%) presented with cirrhosis, including 44% of patients with ALD. CONCLUSIONS: Extrapolating from this population-based surveillance network to the adult U.S. population, approximately 150,000 patients with CLD were diagnosed in gastroenterology practices each year during 1999-2001. Most patients had hepatitis C; heavy alcohol consumption among these patients was common. Almost 20% of patients, an estimated 30,000 per year, had cirrhosis at presentation. These results provide population-level baseline data to evaluate trends in identification of patients with CLD in gastroenterology practices.

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.

Mitchell DG, Navarro VJ, Herrine SK, Bergin D, Parker L, Frangos A, McCue P, Rubin R. · Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA. · Abdom Imaging. · Pubmed #17387539 No free full text.

Abstract: BACKGROUND: We prospectively examined unenhanced MR imaging findings in relation to pathologic fibrosis, inflammation and steatosis in patients with compensated chronic hepatitis C viral infection (HCV). METHODS: Unenhanced MRI at 1.5 T was obtained within one month of core liver biopsy in 64 consecutive candidates for antiviral therapy for compensated HCV. Two pathologists independently graded inflammatory activity index (HAI) and steatosis, and staged fibrosis (grades 0-6). Morphologic MRI findings of cirrhosis, periportal lymph nodes, and MR fat signal ratio from dual gradient echo images were assessed independently by two radiologists blinded to clinical data. MRI and laboratory liver function results were correlated with pathologic results, using Spearman correlation coefficient and stepwise multiple regression. RESULTS: MR fat signal ratio correlation coefficient with pathologic steatosis was 0.71 (p < 0.0001). Coefficients with fibrosis stage were highest for surface nodularity (r (s) = 47, p < 0.0001) and expanded gallbladder fossa (r (s) = 0.42, p = 0.0006). Coefficients with HAI were highest for lymph node size (r (s) = 0.355, p = 0.0040), surface nodularity (r = 0.47, p < 0.0001), expanded gallbladder fossa (r = 0.332, p = 0.0073), and caudate/right lobe ratio (r = 0.326, p = 0.0110). Combined lab and MRI variables provided the best prediction of fibrosis stage (r (2) = 0.656) and HAI (r (2) = 0.597). CONCLUSIONS: A combination of MRI and laboratory findings was most predictive of fibrosis and inflammation.

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.

Trooskin SB, Hadler J, St Louis T, Navarro VJ. · The Connecticut Emerging Infections Program, The Connecticut Department of Public Health, Yale University School of Medicine, New Haven, CT, USA. · Public Health. · Pubmed #16084545 No free full text.

Abstract: OBJECTIVES: This study aimed to use geographic information systems (GIS) that facilitate analysis of associations between location, environment and disease to document the non-random distribution of hepatitis C, identify infection cluster areas, and describe the demographic characteristics of those areas. METHODS: Spatial analysis was conducted of newly reported positive hepatitis C test results using the Connecticut Hepatitis C Reporting Database. A complete database of unduplicated hepatitis C laboratory reports that were sent to the Connecticut Department of Public Health during 1999 was created. Spatial filtering was used to eliminate random noise generated by sparsely populated towns or small number of cases per town. Cluster analysis was used to determine whether cases of hepatitis C virus (HCV) infection tend to occur closer in space to other cases than would be expected by chance alone. The demographic attributes of identified clusters of HCV-positive reports were examined. RESULTS: Areas with the highest concentration of HCV reports roughly correspond to the major metropolitan areas of Connecticut. Six significant clusters of HCV reports were identified in Connecticut. Four of the six clusters identified were located in the most densely populated and most urban areas of the state. All but one identified cluster had been described previously as areas of substantial injection drug use, as indicated by their designation as five of the sites of syringe exchange programmes in Connecticut. This finding suggests that geospatial analysis may assist in the identification of clusters that would not otherwise be suspected based on local demographics or other characteristics. CONCLUSIONS: These findings contribute significantly to the understanding of the state-specific epidemiology of HCV infection. This methodology can be applied wherever a similar database exists to enable the implementation of targeted prevention and educational campaigns to raise awareness of HCV risk factors, the importance of being tested, and treatment options.

Navarro VJ, St Louis TE, Bell BP. · Jefferson Medical College, Philadelphia, Pennsylvania, USA. · J Clin Gastroenterol. · Pubmed #12702988 No free full text.

Abstract: BACKGROUND: Primary care providers (PCPs) must identify persons at risk for hepatitis C virus (HCV) infection, test them correctly, refer to subspecialists, and use published guidelines. The objectives of this study were to describe HCV practices of New Haven County PCPs. STUDY: All 652 PCPs in New Haven County, Connecticut, were surveyed to determine practices related to hepatitis C, including risk factor ascertainment, testing routines, use of published guidelines, and referral practices. RESULTS: Of 181 eligible respondents, 143 (79%) were internal medicine physicians and 38 (21%) were family practitioners. Eighty-four PCPs (46%) routinely asked about a history of blood transfusion, and 112 (62%) routinely asked about a history of injection drug use (IDU). Most PCPs would test current or past IDU (91% versus 83%, respectively), persons transfused prior to 1992 (79%), health care workers with a history of a needle stick accident (88%), and a child born to an HCV-infected mother (76%). PCPs frequently referred patients with hepatitis C to gastroenterologists. Most PCPs (76%) were familiar with available hepatitis C testing guidelines. CONCLUSIONS: Most PCPs test for HCV infection appropriately, but many do not elicit risk factor histories that could identify such persons. More effective training with emphasis on eliciting a history of pertinent risk factors is needed.

Saxena R, Crawford JM, Navarro VJ, Friedman AL, Robert ME. · Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. · Mod Pathol. · Pubmed #12218206 links to  free full text

Abstract: BACKGROUND: The distinction between acute rejection and early recurrent hepatitis C infection (RHCV) in the setting of orthotopic liver transplantation is often difficult. In liver biopsies acidophil bodies and lobular hepatitis are used to suggest a diagnosis of RHCV over rejection, however, the reliability of this practice has not been established. Because portal tract changes in RHCV and rejection often overlap, we sought to determine whether the degree of hepatocyte acidophil body formation seen on liver biopsies could be used to distinguish between these two conditions. METHODS: Quantification of acidophil bodies was performed on liver biopsies in orthotopic liver transplant patients with RHCV (n = 10), non-hepatitis C orthotopic liver transplant patients with uncomplicated rejection episodes (n = 10) and non-transplant patients with chronic hepatitis C infection (n = 10). Hematoxylin and Eosin stained slides from all three groups were randomized and tissue segments 1.0 cm in length and of variable width (0.04-0.13 cm) were examined at 200x magnification in a blinded fashion by two pathologists in order to quantify the number of acidophil bodies/cm(2). Lobular chronic inflammation was also graded on a 0-3+ scale. RESULTS: Liver biopsies taken at the onset of RHCV exhibited 606 +/- 101 acidophil bodies/cm(2) (mean +/- standard error of mean, range 200-1390). These counts were significantly greater (P =.0061, paired 2-tailed t-test) than the 241 +/- 53 acidophil bodies/cm(2) (range 80-514) for acute rejection, and the 194 +/- 21 acidophil bodies/cm(2) (range 100-333) for non-liver transplant chronic hepatitis C infection (P =.0013). No difference in lobular inflammation between index RHCV and rejection biopsies was detected. CONCLUSIONS: Although there is overlap, on average there are twice as many acidophil bodies in the initial stage of RHCV when compared with acute rejection (average of 55 per linear cm in RHCV versus 21 per linear cm for rejection). Lobular inflammation was not a reliable indicator of the initial onset of RHCV.