Hepatitis: Herrine SK

Herrine SK, Friedman LS. · No affiliation provided · J Hepatol. · Pubmed #16046025 No free full text.

This publication has no abstract.

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.

Baig NA, Herrine SK, Rubin R. · Division of Gastroenterology and Hepatology, Jefferson Medical College, Philadelphia, Pennsylvania, USA. · Clin Lab Med. · Pubmed #11321935 No free full text.

Abstract: The liver plays an important role in the pathogenesis of NIDDM. More importantly to the clinician is the myriad of situations in which the care of the patient with diabetes is affected by or causes an effect to the liver. Patients with underlying diabetes can present with abnormal liver chemistries, which can represent findings as benign as hepatic steatosis or as severe as cirrhosis of the liver. The medications used to treat diabetes can be potent hepatotoxins. Several primary liver diseases are associated with increased risk of the development of diabetes. Epidemiologically, there seems to be a correlation between diabetes mellitus, the most common endocrinologic disease, and hepatitis C, the leading cause of chronic liver disease in the United States. In the management of end-stage liver disease, both cirrhosis and orthotopic liver transplantation promote glucose intolerance and diabetes in a number of patients through various mechanisms including insulin resistance and impaired insulin secretion. These relationships highlight both the importance of the liver as an endocrine organ and the multisystem aspects of the patient with diabetes mellitus.

Armenti VT, Herrine SK, Radomski JS, Moritz MJ. · Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA. · Liver Transpl. · Pubmed #11084052 links to  free full text

Abstract: The first known posttransplantation pregnancy was in 1958 in a renal transplant recipient who had received a kidney from her identical twin sister. The first known posttransplantation pregnancy in a liver transplant recipient was in 1978. Information available from female kidney transplant recipients helped in the decision making involved in the management of this case, as well as those that followed. Over the last 20 years, issues specific to liver transplantation and pregnancy have been identified. Similar to the kidney transplant recipient population, when prepregnancy recipient graft function is stable and adequate, pregnancy appears to be well tolerated. Also similar to kidney transplant recipients, there has been no evidence of a specific malformation pattern among the children, and although prematurity and low birth weight occur, overall newborn outcomes have been favorable. Pregnancy in the setting of recurrent liver disease, such as recurrent hepatitis C, poses a potential problem among liver transplant recipients, as well as the possible adverse effects of immunosuppression on maternal kidney function. Also of significance, peripartum graft deterioration has more severe consequences in this transplant recipient population. Therefore, pregnancy must be considered carefully in this transplant recipient group. Since 1991, the National Transplantation Pregnancy Registry (NTPR) has studied the safety of pregnancy outcomes in solid-organ transplant recipients. The purpose of this review is to catalog studies in the literature, as well as to present current data from the registry with management guidelines.

Herrine SK, Brown RS, Bernstein DE, Ondovik MS, Lentz E, Te H. · Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5244, USA. · Dig Dis Sci. · Pubmed #15844708 No free full text.

Abstract: There are no established therapeutic regimens for hepatitis C virus (HCV) patients who relapse following treatment with interferon alpha-2b and ribavirin or those who break through while on interferon alpha-2b and ribavirin. We therefore evaluated various combination therapies in HCV patients who relapsed or experienced a viral breakthrough. Patients (n = 124) were randomized to 48 weeks of treatment with once-weekly subcutaneous injections of 180 microg pegylated (peg-) interferon alpha-2a plus oral ribavirin (800-1000 mg/day), mycophenolate mofetil (2 g/day), amantadine (200 mg/day), or ribavirin and amantadine and followed for an additional 24 weeks. The sustained virologic response was higher in patients administered peginterferon alpha-2a plus ribavirin (38%) or ribavirin and amantadine (45%) than in those administered peginterferon alpha-2a plus mycophenolate mofetil (17%) or amantadine (10%). As in previous studies, patients with genotype non-1 and those with lower viral loads had better responses than those with genotype 1 and high viral loads, though the differences did not reach significance. The four treatment regimens had similar safety profiles, except that patients receiving ribavirin had greater maximal hemoglobin decreases. These findings suggest that the combination of peginterferon alpha-2a plus ribavirin or with ribavirin and amantadine is effective in some HCV patients who relapse after treatment with interferon alpha-2b plus ribavirin.

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.

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.

Nguyen MT, Herrine SK, Laine CA, Ruth K, Weinberg DS. · Fox Chase Cancer Center, Philadelphia, PA 19111, USA. · Arch Intern Med. · Pubmed #16186472 links to  free full text

Abstract: BACKGROUND: Because of the low prevalence of hepatitis C virus (HCV) infection in the general population, mass screening would be expensive and of low yield. Some researchers advocate targeted screening of persons at elevated HCV risk. METHODS: This cross-sectional study aimed to develop a patient-administered tool to assess HCV infection risk. Two hundred seven patients with unknown HCV status from a general medicine practice and 222 HCV-positive patients from a hepatology practice completed a 72-item survey about demographic, social, and clinical risk factors for HCV infection. General medicine patients also underwent HCV serologic testing. RESULTS: Three (1.5%) of 207 general medicine patients had positive HCV antibody test results. These patients plus the 222 hepatology patients were significantly more likely than HCV-negative patients to report an array of factors. In a multivariable model, 7 factors remained significantly associated with HCV infection: sex with a prostitute or an injecting drug user, exposure to blood products, refusal as a blood donor or as a life insurance applicant, witnessing illicit drug use, and self-reported HBV infection. A simplified model that assigned 1 point for each factor present predicted HCV infection as well as a weighted model (based on chi(2) testing and receiver operating characteristic curve comparison). In a population with a 2% prevalence of HCV infection, people who identified 2 risk factors had a 10% chance of HCV infection, whereas those with 4 or more risk factors had a 50% chance. CONCLUSIONS: A self-administered 72-item questionnaire can stratify patients into HCV risk groups. If validated in other primary care populations, this instrument could help target HCV screening.

Kaul V, Friedenberg FK, Braitman LE, Anis U, Zaeri N, Fazili J, Herrine SK, Rothstein KD. · Office for Research and Technology Development, Department of Pathology, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA. · Am J Gastroenterol. · Pubmed #12385450 No free full text.

Abstract: OBJECTIVE: Although noninvasive markers predictive of cirrhosis in patients with chronic hepatitis C have been examined, none has proved sufficiently accurate for clinical use. The aim of this study was to develop an accurate model that can be easily used by clinicians to predict the probability of cirrhosis in hepatitis C patients from readily available clinical and laboratory information. METHODS: We identified 264 consecutive patients with established chronic hepatitis C infection and extracted multiple physical examination and biochemical variables (recorded before liver biopsy). Similar data were extracted from charts at another hospital. RESULTS: Logistic regression identified the following independent predictors of cirrhosis: platelet count < or = 140,000/ mm3, spider nevi, AST > 40 IU/L, and male gender. Male and female patients with normal values for platelet count and AST and no spider nevi had low probabilities of cirrhosis: 1.8% (95% CI = 0.4-7) and 0.03% (95% CI = 0.003-0.04), respectively. Male patients with abnormal values on all three other predictors had a probability of cirrhosis of 99.8% (95% CI = 98.7-100). Over 48% of study patients had a low (< or = 1.8%) or a very high (> or = 99.8%) predicted probability of cirrhosis. The model had area under the receiver operating characteristic curve of 0.938 (95% CI = 0.91-0.97) and 93.4% in an internal validation. The model accurately distinguished patients with and without cirrhosis (area under the receiver operating characteristic curve = 93.3%) in 102 hepatitis C patients from another hospital. CONCLUSIONS: In patients with hepatitis C, four readily available variables together predict cirrhosis accurately. Successful validation in hepatitis C patients at another hospital with lower prevalence of cirrhosis suggests this model's potential for broad applicability.

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.

Zhang XM, Mitchell DG, Shi H, Holland GA, Parker L, Herrine SK, Pasqualin D, Rubin R. · Department of Radiology, Thomas Jefferson University, 1096 Main Bldg., 132 S. 10th St., Philadelphia, PA 19107, USA. · AJR Am J Roentgenol. · Pubmed #12130443 links to  free full text

Abstract: OBJECTIVE: To study the MR appearance of lymph nodes in relation to activity of chronic active hepatitis C, we correlated the findings on MR imaging with a histologic grading of the activity level. MATERIALS AND METHODS: Fifty patients with chronic active hepatitis C, who had MR imaging examinations and a related histology report from a liver biopsy obtained within 1 month of the MR imaging were chosen from our radiology database and studied retrospectively. All patients were examined over a 4-year period at a single institution to detect cirrhosis or hepatocellular carcinoma. We divided the 50 patients into the mild, moderate, or severe activity groups, according to their histology reports. Two radiologists, unaware of the histologic classifications, individually reviewed the MR images to observe the perihepatic locations, number, size (defined as the sum of the length-by-width products of the largest three nodes), and intensity of the lymph nodes relative to the spleen. The clinical records of the patients were reviewed to check the results of their liver function tests. The lymph node findings on MR imaging were compared with the histologically confirmed activity level of chronic hepatitis C. RESULTS: Forty-four (88.0%) of 50 patients had perihepatic lymph nodes larger than 5 mm on MR images, including 64.2% (9/14) of the patients with mild activity, 96.3% (26/27) of the patients with moderate activity, and 100% (9/9) of the patients with severe activity (p = 0.0034). The average number +/- the standard deviation (SD) of perihepatic lymph nodes was 2.5 +/- 1.8 in patients with mild activity, 5.6 +/- 2.2 in patients with moderate activity, and 8.3 +/- 3.5 in patients with severe activity (p = 0.0001). The average size (+/- SD) of the lymph nodes was 151.0 +/- 104.9 mm(2) in the mild activity group, 366.8 +/- 143.0 mm(2) in the moderate activity group, and 488.2 +/- 244.8 mm(2) in the severe activity group (p = 0.0001). On fat-saturated fast spin-echo T2-weighted MR images, the average number (+/- SD) of hyperintense nodes was 0.17 +/- 0.25 in the mild activity group, 1.7 +/- 0.80 in the moderate activity group, and 2.4 +/- 0.60 nodes in the severe activity group (p = 0.0001). No relationship between histologic activity and results from liver function tests was found. CONCLUSION: MR imaging depicts perihepatic lymph nodes in most patients with chronic hepatitis C. Lymph node number, size, and hyperintensity were related to the activity of chronic hepatitis C, but the results of liver function tests were not.

Herrine SK. · Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Ann Intern Med. · Pubmed #12020143 links to  free full text

Abstract: Chronic hepatitis C virus (HCV) infection is common and often asymptomatic. Antibodies against HCV are a highly sensitive marker of infection. Molecular testing for HCV is used to confirm a positive result on antibody testing and to provide prognostic information for treatment; however, quantitative HCV RNA does not correlate with disease severity or risk for progression. Chronic HCV infection is most frequently associated with remote or current intravenous drug use and blood transfusion before 1992, although as many as 20% of infected patients have no identifiable risk factor. In an estimated 15% to 20% of persons infected with HCV, the infection progresses to cirrhosis; alcohol intake is an important cofactor in this progression. Most specialists prefer to include an examination of liver histology in the management of patients with chronic HCV infection to aid prognostic and treatment decisions. The current standard of pharmacologic treatment of chronic HCV is weekly subcutaneous peginterferon in combination with daily oral ribavirin, which results in sustained virologic response in approximately 55% of chronically infected patients. Side effects of interferon therapy include myalgias, fever, nausea, irritability, and depression. The cost-effectiveness of interferon therapy is similar to that of many commonly accepted medical interventions. The primary care physician serves a vital role in identifying patients with chronic HCV infection, educating patients about risk factors for transmission, advising patients about the avoidance of alcohol, and aiding patients in making treatment decisions.

Siler CA, McGettigan JP, Dietzschold B, Herrine SK, Dubuisson J, Pomerantz RJ, Schnell MJ. · The Dorrance H. Hamilton Laboratories, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Virology. · Pubmed #11878905 No free full text.

Abstract: A highly attenuated, recombinant rabies virus (RV) vaccine strain-based vector was utilized as a new immunization strategy to induce humoral and cellular responses against hepatitis C (HCV) glycoprotein E2. We showed previously that RV-based vectors are able to induce strong immune responses against human immunodeficiency virus type I (HIV-1) antigens. Here we constructed and characterized three replication-competent RV-based vectors expressing either both HCV envelope proteins E1 and E2 or a modified version of E2 which lacks 85 amino acids of its carboxy terminus and contains the human CD4 transmembrane domain and the CD4 or RV glycoprotein cytoplasmic domain. All three constructs stably expressed the respective protein(s) as indicated by Western blotting and immunostaining. Moreover, surface expression of HCV E2 resulted in efficient incorporation of the HCV envelope protein regardless of the presence of the RV G cytoplasmic domain, which was described previously as a requirement for incorporation of foreign glycoproteins into RV particles. Killed and purified RV virions containing HCV E2 were highly immunogenic in mice and also proved useful as a diagnostic tool, as indicated by a specific reaction with sera from HCV-infected patients. In addition, RV vaccine vehicles were able to induce cellular responses against HCV E2. These results further suggest that recombinant RVs are potentially useful vaccine vectors against important human viral diseases.

Nazarian LN, Feld RI, Herrine SK, Webner D, Lev-Toaff AS, Johnson PT, Storey LA, Needleman L. · Department of Radiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5244, USA. · J Ultrasound Med. · Pubmed #10944039 No free full text.

Abstract: Sonographic guidance is commonly used in the biopsy of focal hepatic lesions, but biopsy for diffuse disease is often non-image-guided. We evaluated the safety and efficacy of real-time sonographically guided random core biopsy in the assessment of diffuse liver disease in 210 patients. The two most common indications for biopsy were viral hepatitis (in 113 patients) and elevated liver function test results of unknown cause (in 54 patients). Ultrasonography and pathology reports were reviewed retrospectively to determine number of needle passes and final diagnoses. Adequate tissue was obtained in all 210 patients, with 259 of 269 (96%) passes having been successful. Specimens were submitted for light microscopy and other tests as indicated. No difference in success rates was found for right and left lobe biopsies. No major complications occurred. Minor complications occurred in 10 of 210 (4.8%) patients and were self-limited. Sonographically guided core liver biopsy is a safe and effective method for the diagnosis of liver disease.