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Biomedical subjects

Nanda Kerkar

Publications and source records attributed to Nanda Kerkar.

12 recordsLinked to original sources
PubMed2006

The hepatic fibrocystic diseases.

The hepatic fibrocystic diseases present with variable intrahepatic biliary abnormalities, which range from portal tract enlargement and fibrosis to cystic formations. They may present as autosomal recessive or dominant polycystic kidney diseases, with associated dilatation of the renal collecting system, or as incompletely characterized cystic diseases. Symptoms from the liver disease often result from complications of fibrosis or dilated ducts/cyst (sludge, lithiasis, infection). The treatment is supportive, with careful attention to associated renal disease. Liver transplantation is an option in selected patients.

Caroli Disease↗
PubMed2006

Hepatitis C in children: a quaternary referral center perspective.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection affects 0.3% of children in the United States, and the general impression is that it has a benign course in childhood. We analyzed a pediatric population with chronic HCV in a quaternary referral center. MATERIAL AND METHODS: This is a retrospective clinical review comprising all patients with chronic HCV referred to the Pediatric Liver/Liver Transplant Program between January 1999 and December 2004. RESULTS: Ninety-one patients (52% female; mean age, 9 years) were assessed. Eight-three percent of the patients were genotype 1. Twenty-one patients received/are receiving interferon and ribavirin for chronic HCV (treatment indications--advanced disease, 9; clinical trial, 6; genotype 2, 2; social, 2; prerenal transplant, 1). Eight (53%) of 15 patients, who have completed therapy and follow-up, achieved sustained viral response. Seven of 91 patients had cirrhosis at presentation (mean age, 11.7 years). Four underwent liver transplantation, all experienced HCV recurrence, 2 died, 1 was retransplanted, and 1 has compensated cirrhosis. CONCLUSION: Although, in general, HCV in children has a slow progression, there are cases with an accelerated course and early development of cirrhosis requiring liver transplant. Hepatitis C virus recurs universally after transplant, and its prognosis is usually poor; therefore, the most promising long-term approach is to clear this infection before transplantation.

Adolescent↗
PubMed2005

Pediatric inflammatory myofibroblastic tumor with late metastasis to the lung: case report and review of the literature.

Inflammatory myofibroblastic tumors (IMTs) are challenging lesions with respect to classification, differential diagnosis, and biologic potential. In children, extrapulmonary IMTs, particularly those from the abdomen or mesentery, are generally aggressive, with frequent local recurrences. There are few documented patients with distant metastasis, and most of these had metastases at presentation or developed metastases within months to a few years. We add to the short list of metastatic extrapulmonary IMTs a pediatric patient in whom the primary lesion was widespread in the abdomen at presentation and metastatic disease to the lung was diagnosed 9 years after the primary resection. We describe the clinical and pathologic features of this patient and review the characteristics of extrapulmonary IMTs with distant metastasis reported in the literature.

Abdominal Neoplasms↗
PubMed2005

Parents and clinicians underestimate distress and depression in children who had a transplant.

The present study examined whether there are differences in reporting of depressive and post-traumatic stress symptoms between children who had a transplant and children who had other medical illnesses. We evaluated both the child's report about her/his symptoms and the parent or the clinician's report about these symptoms in the child. Scores on measures of depression (clinician rated vs. child rated) and post-traumatic stress (parent rated vs. child rated) were compared between medically ill children who have vs. have not had a solid organ transplant. The findings of a psychiatric evaluation are also reported. Children who have vs. have not received a solid organ transplant reported the same levels of depression and post-traumatic stress, while adults (their parents or clinicians who evaluated them) reported lower levels of depression and post-traumatic stress in the transplant group. The psychiatric evaluation revealed no differences between the groups. Children view their post-transplant course differently from adults caring for these children. Adults tend to underestimate the child's post-transplant emotional symptoms, possibly because they focus on the improved prognosis (whereas the children focus on the concrete experience of illness). The child's report of his or her emotional symptoms should be directly sought post-transplant.

Adolescent↗
PubMed2005

Hepatitis B in children: complexities in management.

Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for > or =6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to <5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.

Antiviral Agents↗
PubMed2005

Rapamycin successfully treats post-transplant autoimmune hepatitis.

Rapamycin (Rapa), one of the newer immunosuppressants has been found to control and prevent autoimmune features in animal models. This is the first report describing the successful control of post-transplant autoimmune hepatitis (AIH) with Rapa. Post-transplant AIH is diagnosed in the presence of raised transaminases, elevated immunoglobulin G, presence of autoantibodies and histologic changes consistent with AIH on liver biopsy. It may represent a recurrence of the original AIH that led to transplantation or present as a de novo AIH after liver transplant. Post-transplant AIH has conventionally been treated with Prednisolone (Pred) and Azathioprine (AZA). In this report, tailoring of immunosuppression after diagnosis of post-transplant AIH is described with special emphasis on those treated successfully with Rapa. Fifteen of 21 patients responded to treatment with an increase in dose of Pred and addition of AZA or Mycophenolate Mofetil (MMF) to calcineurin inhibitor. Five non-responders and one other patient with post-transplant AIH were treated with addition of Rapa. All six responded to treatment but drug was withdrawn in one patient. Adverse events were minimal. Rapa may prove to be an important addition in the control of autoimmune liver disease.

Autoantibodies↗
PubMed2004

Medication adherence in pediatric and adolescent liver transplant recipients.

OBJECTIVE: Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated. METHODS: We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days. RESULTS: An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited. CONCLUSIONS: Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.

Adolescent↗
PubMed2003

Cytochrome P4502D6(193-212): a new immunodominant epitope and target of virus/self cross-reactivity in liver kidney microsomal autoantibody type 1-positive liver disease.

Cytochrome P4502D6 (CYP2D6), target of liver kidney microsomal autoantibody type 1 (LKM1), characterizes autoimmune hepatitis type 2 (AIH2) but is also found in patients with chronic hepatitis C virus (HCV) infection. To provide a complete linear epitope B cell map of CYP2D6, we tested peptides spanning the entire sequence of CYP2D6. In addition to confirming previously described antigenic sites, we identified four new epitopes (193-212, 238-257, 268-287, and 478-497). CYP2D6(193-212) is immunodominant and was the target of 12 of 13 (93%) patients with AIH2 and 5 of 10 (50%) HCV/LKM1-positive patients. Because LKM1 is present in both AIH2 and a viral infection, we tested whether Abs to CYP2D6(193-212) arise through cross-reactive immunity between virus and self. We identified a hexameric sequence "RLLDLA" sharing 5 of 6 aa with "RLLDLS" of HCV(2985-2990) and all 6 aa with CMV(130-135). Of 17 CYP2D6(193-212)-reactive sera, 11 (7 AIH and 4 HCV) reacted by ELISA with the HCV homologue, 8 (5 AIH and 3 HCV) with the CMV homologue, and 8 (5 AIH and 3 HCV) showed double reactivity. Autoantibody binding to CYP2D6(193-212) was inhibited by preincubation with HCV(2977-2996) or CMV(121-140). Recombinant HCV-nonstructural protein 5 and CMV-UL98 proteins also inhibited Ab binding to CYP2D6(193-212). Affinity-purified CYP2D6(193-212)-specific Ab inhibited the metabolic activity of CYP2D6. The demonstrated similarity and cross-reactivity between CYP2D6(193-212) and two unrelated viruses suggests that multiple exposure to viruses mimicking self may represent an important pathway to the development of autoimmunity.

Adolescent↗
PubMed2002

Key residues of a major cytochrome P4502D6 epitope are located on the surface of the molecule.

Eukaryotically expressed CYP2D6 is the universal target of liver kidney microsomal Ab type 1 (LKM1) in both type 2 autoimmune hepatitis (AIH) and chronic hepatitis C virus (HCV) infection. In contrast, reactivity to prokaryotically expressed CYP2D6 protein and synthetic peptides is significantly lower in HCV infection than in AIH. The aim of the present study was to characterize LKM1 reactivity against a panel of eukaryotically expressed CYP2D6 constructs in the two conditions. LKM1-positive sera obtained from 16 patients with AIH and 16 with HCV infection were used as probes to perform a complete epitope mapping of CYP2D6. Reactivity to the full-length protein and 16 constructs thereof was determined by radioligand assay. We found that antigenicity is confined to the portion of the molecule C-terminal of aa 193, no reactivity being detectable against the aa sequence 1-193. Reactivity increases stepwise toward the C-terminal in both AIH and HCV, but the frequency of reactivity in the two conditions differs significantly between aa 267-337. To further characterize this region, we introduced a five and a three amino acid swap mutation selected from the homologous regions of CYP2C9 and HCV. This maneuver resulted in a substantial loss of LKM1 binding in both conditions, suggesting that this region contains a major epitope. Molecular modeling revealed that CYP2D6(316-327) is exposed on the surface of the protein, and may represent a key target for the autoantibody. These findings provide an initial characterization of the antigenic constitution of the target of LKM1 in AIH and HCV infection.

Adolescent↗