Esra Erden

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon

Summary.  Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment‐naïve, 14 had previously used IFN), efficacy of 1‐year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment‐naïve patients. In both treatment‐naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN–LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN ± LAM than with LAM alone (P < 0.05). In treatment‐naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Clinical trial: insulin‐sensitizing agents may reduce consequences of insulin resistance in individuals with non‐alcoholic steatohepatitis

Background  Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis.

Famciclovir treatment of chronic delta hepatitis

BACKGROUND/AIMS Interferon is the only established therapy for chronic delta hepatitis and alternative treatment options are an urgent need. Since successful treatment of a case of post-transplant delta hepatitis with the nucleoside analogue famciclovir had been reported, a pilot study was undertaken to evaluate the use of famciclovir in the treatment of chronic delta hepatitis. METHODS A total of 15 adult patients, 13 men, two women, ages 20-52 years, with chronic delta hepatitis were treated with famciclovir, 500 mg, three times a day for 6 months and were then followed-up for 6 months posttreatment. All patients had compensated chronic liver disease, elevated liver enzymes and were hepatitis delta virus (HDV) RNA positive by polymerase chain reaction at baseline. Patients were monitored and tested for HBsAg, hepatitis B virus (HBV) DNA and HDV RNA levels. Liver biopsies were obtained before starting famciclovir and within 1 month of completion of treatment. RESULTS HBV DNA levels decreased in nine of the 15 patients and levels rose again after treatment (P<0.05). Famciclovir had no effect on alanine aminotransferase (ALT) and HBsAg levels or on serum HDV RNA and overall, there was no improvement in liver histology. CONCLUSIONS Treatment of chronic delta hepatitis with famciclovir has no effect on disease activity and HDV RNA levels.

Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases

The role of calcium independent inducible nitric oxide synthase (iNOS) in breast carcinoma is controversial, and the implications of iNOS expression on prognosis are not known. In this study, we aimed to investigate the significance of immunohistochemical iNOS expression in 100 invasive ductal carcinomas. In addition, 11 normal breast tissues, 20 cases of usual ductal hyperplasias (UDHs) and 20 fibroadenomas were included. We found that 78% of malignant and 75% of benign cases showed iNOS immunoreactivity. However, the intensity and the quantity of iNOS expression were significantly higher in the cancer group when compared with benign breasts (P<0.001), suggesting a role of iNOS in breast carcinogenesis. We were unable to show a correlation between iNOS expression and tumor grade, axillary lymph node status, and estrogen receptor expression. In 50 axilla negative cases having 5–12 years follow-up, disease free survival (DFS) rate was significantly lower in cases showing strong iNOS expression (P=0.05). As strong iNOS expression was correlated with short DFS, we concluded that further studies would be necessary to elucidate if iNOS expression might be a useful prognostic marker in breast carcinoma, especially in the axilla negative group.

Lamivudine vs lamivudine and interferon combination treatment of HBeAg(−) chronic hepatitis B

Summary.  To determine whether combination treatment of HBeAg(−) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(−), HBV DNA‐positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine–interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug‐free follow‐up (short‐ and long‐term follow‐up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real‐time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono‐ and combination treatment, respectively. Corresponding virologic responses at short‐ and long‐term follow‐up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value ≥200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficay of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Levofloxacin-Induced Acute Fulminant Hepatic Failure in a Patient with Chronic Hepatitis B Infection

OBJECTIVE: To report a case of possible levofloxacin-induced acute fulminant hepatic failure. CASE SUMMARY: An unconscious 55-year-old woman was hospitalized with the diagnosis of hepatic encephalopathy. The patient had received levofloxacin 500 mg daily for 10 days because of an upper respiratory infection. Her past medical history revealed hepatitis B surface antigen positivity as an asymptomatic hepatitis B virus carrier for 10 years. After hospitalization, treatment included plasmapheresis and supportive care. The patients consciousness improved on the second day of treatment. Other etiologies of fulminant hepatic failure were ruled out, suggesting levofloxacin-induced fulminant hepatic failure. Although the patient received supportive treatment, her condition gradually deteriorated and she died 12 weeks after admission to our hospital. An objective causality assessment revealed that the adverse event was possibly related to levofloxacin. DISCUSSION: Levofloxacin is widely used because of its broad spectrum of antimicrobial activity. As of August 9, 2005, to our knowledge, only one case of fulminant hepatic failure in relation to levofloxacin has previously been published. We believe that, in our patient, the relationship between levofloxacin and her illness is clear because of the negative results in the etiological studies, the short time between the drugs administration and the development of disease, and the pathologic findings suggestive of drug-induced hepatitis. CONCLUSIONS: Clinicians should be aware of the possibility of severe hepatic injury associated with levofloxacin when prescribing this drug.

Spinal Intradural-Intramedullary Cavernous Malformation

Cavernous angiomas or cavernomas are uncommon vascular malformations of the central nervous system and spinal involvement is much rarer especially in pediatric patients. We report a case of spinal intradural-intramedullary cavernous angioma in a 14-year-old male child. The cavernoma was located at the level of C6–C7 at the dorsal part of the spinal cord. The diagnosis was made with MRI and the patient underwent surgical treatment. The cavernoma was totally removed with laminotomy and microsurgical techniques. Somatosensory evoked potential monitoring was also used peroperatively. The clinical, radiological and surgical features of this rare case were presented and discussed with reference to the literature.

Recipient-derived hepatocytes in sex-mismatched liver allografts after liver transplantation: Early versus late transplant biopsies

Background. The presence of microchimerism in transplanted tissues is well defined; however, the timeframe of appearance and disappearance of engraftment in liver allograft is unknown. The aims of this study were to analyze for the presence of “recipient-derived cells” in sex-mismatched individuals after liver transplantation, comparing the frequency of “recipient-derived cell repopulation” in early versus late transplant biopsies and to evaluate the relationship between “recipient-derived cell repopulation” and the severity of graft injury. Methods. Paraffin-embedded liver biopsy samples of 18 recipients were reviewed. Sixteen of them were obtained from recipients with sex-mismatched donors. The remaining two were obtained from recipients with sex-matched donors and were used as controls. Immunohistochemistry and fluorescence in situ hybridization double-labeling method were performed on pretreated slides using anti-human hepatocyte antibody to identify hepatocytes, a mouse anti-human cytokeratin-7 to identify ductal epithelial cells, and using CEPX/Y DNA probes for visualizing X and Y chromosomes. The double-labeled slides were examined systematically using an image analyzer system. Results. The mean time from transplantation to biopsy was 8.1 months. Eleven of the 16 samples obtained from recipients with sex-mismatched grafts demonstrated “recipient-derived hepatocyte repopulation,” comprising a mean of 2.1% of the hepatocytes. In the control biopsies, none of the cells demonstrated different nuclear signals from the donor’s sex origin. The presence and proportion of “recipient-derived hepatocyte repopulation” rate were significantly higher in early transplant biopsies than in late transplant biopsies (P<0.05). Conclusion. Some hepatocytes of sex-mismatched liver grafts were replaced by “recipient-derived cells” during injury. Such repopulation is more common in the early liver-graft biopsies. The severity of acute cellular rejection appears to have no effect on the rate of recipient-derived repopulation.

Nuclear localization of hepatitis B core antigen and its relations to liver injury, hepatocyte proliferation, and viral load

Goals The aim of this study was to determine the factor(s) independently affecting the HBcAg expression pattern in HBV-infected livers. Background Subcellular localization of HBcAg have been found to be related to the activity of liver disease, hepatocyte proliferation rate and the level of HBV replication. Study A total of 98 patients with biopsy proven chronic hepatitis B were included. HBcAg and proliferative cell nuclear antigen (PCNA) were immunohistochemically detected. HBcAg expression and its relationship with histologic activity index, ALT levels, PCNA score and HBV DNA levels were investigated. Results Forty-three (44%) patients were positive for HBcAg staining, with most of them (37 patients) having nuclear localization. Forty-seven percent of patients with detectable HBV DNA had nuclear staining while none of the HBV DNA negative patients had nuclear staining (P < 0.0005). Patients with positive nuclear staining had lower HAI (<8) and a lower PCNA score (<353/1,000 cell) than those with negative staining (62% vs. 39% and 90% vs. 66%, respectively, P < 0.05). In multivariate analysis, both high HBV DNA level and low HAI (P < 0.0005 and P < 0.05, respectively) but not PCNA score, were independently associated with nuclear staining of HBcAg. Conclusions Our results suggest that viral load and the severity of liver damage but not the rate of hepatocyte proliferation independently affects the HBcAg expression pattern.

Differential diagnosis of idiopathic inflammatory trigeminal sensory neuropathy from neuroma with a biopsy: case report.

OBJECTIVE AND IMPORTANCE Idiopathic inflammatory trigeminal sensory neuropathy (IITSN) is a disorder with the dominant clinical features of trigeminal sensory disturbance; this idiopathic condition follows a benign course in most cases. Recent reports have shown that transient abnormalities, which may mimic those of trigeminal neuromas, can be observed in magnetic resonance imaging scans. Presented here is a case of IITSN that was diagnosed, with cytological and histopathological verification, during the active inflammatory phase of the disease (the first such attempt, to our knowledge). CLINICAL PRESENTATION A 20-year-old female patient was referred to our hospital with a 2-month history of numbness of the left side of her face, headache, and hemifacial pain attacks. Cranial magnetic resonance imaging scans revealed a mass above and below the foramen ovale, extending into the cavernous sinus. INTERVENTION A percutaneous biopsy procedure through the foramen ovale was performed; the pathological examination revealed lymphocytes, macrophages, and endothelial cells but no evidence of neoplastic cells. A few days later, the patient was surgically treated using a cranial base approach, the gasserian ganglion was exposed, and the lesion was removed. Pathological examination of the specimens revealed inflammatory changes and fibrosis of the nerve fibers and ganglion cells. Disruption of the myelin around the nerve bundles was detected. Therefore, IITSN was pathologically confirmed during the early stage of the disease. During 3 months of follow-up monitoring, the patient experienced no serious clinical problems. CONCLUSION IITSN should be suspected in cases of tumors involving the cavernous sinus, and a percutaneous biopsy through the foramen ovale should be performed as part of the differential diagnosis in such cases. This procedure might obviate unnecessary aggressive surgery. In the current case, no neoplastic cells were observed during the examination; only lymphocytes, macrophages, and endothelial cells were observed, on a background of erythrocytes. Lymphocyte-dominant inflammatory infiltration, fibrotic changes, and demyelinization are cardinal histopathological findings observed during the active phase of IITSN.