Ganciclovir for Severe Cytomegalovirus Primary Infection in an Immunocompetent Child

Described here is the unusual case of a previously healthy 17-month-old girl who developed severe cytomegalovirus (CMV) disease with prolonged fever and hepatitis. The severity of her illness required hospitalization and prompted antiviral treatment. Short-term intravenous ganciclovir treatment was associated with immediate and sustained resolution of the symptoms as well as a sharp decrease of CMV viremia. This observation suggests that antiviral therapy might be considered in select cases of severe primary CMV infection in immunocompetent childre

Anticoagulant therapy for nodular regenerative hyperplasia in a HIV-infected patient

<p>Abstract</p> <p>Background</p> <p>Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed.</p> <p>Case Presentation</p> <p>Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient.</p> <p>Conclusions</p> <p>Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment.</p

Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis

Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be studied in detail by molecular techniques. We describe a case of extensive intrahepatic biliary dysplasia, with lesions ranging from BilIN-1 to BilIN-3 lesions, and multifocal microscopic ICC in hepatitis C virus (HCV)- and alcohol-related cirrhosis. The small ICC foci had remained undetected prior to transplantation. Fluorescence in situ hybridization (FISH) analysis was performed on three foci of BilIN-3 lesions and on three microinvasive ICC foci with a combination of three FISH probes directed against genes frequently altered in pancreatic and biliary tract carcinomas. FISH analysis revealed a CDKNA2 heterozygous deletion in one BilIN-3 focus, and in one non-contiguous ICC focus, although the deletion was just above the chosen threshold. No deletions were detected in the genomic regions encoding TP53 and SMAD4. This report documents for the first time the development of multifocal ICC in the setting of extensive biliary dysplasia in a patient with three risk factors, HCV infection, alcohol abuse, and cirrhosis, and suggests heterogeneous carcinogenesis in ICC and possible involvement of the CDKNA2 gen

Neoadjuvant Chemotherapy in Patients with Stage IV Colorectal Cancer: A Comparison of Histological Response in Liver Metastases, Primary Tumors, and Regional Lymph Nodes

Background: We report the histopathological results of a novel "inversed” strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes. Methods: Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3-4months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis. Results: Median age of patients was 56 (range, 37-69) years. Primary tumor location was right colon (n=5), left colon (n=7), and rectum (n=17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [P=0.005]; for the primary tumor and metastases 0.44 [P=0.021]; and for lymph nodes and metastases 0.58 [P=0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P=0.02). Two patients had a complete pathologic response (pT0N0M0). Conclusions: In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherap

Lack of in vivo blockade of Fas- and TNFR1-mediated hepatocyte apoptosis by the hepatitis C virus.

In vitro data have shown that the hepatitis C virus (HCV) core protein binds to protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since this interaction could be relevant to HCV persistence and oncogenesis, this study assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in the liver of 60 chronic hepatitis C patients. Results were compared with the liver disease grading and staging scores and the HCV replication level in serum and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in 35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors. Overall, the numbers of TUNEL-, Fas- and TNFR-positive hepatocytes did not correlate with the extent of intrahepatic CD8+ T-lymphocyte infiltration, the grading and staging of liver disease, or the serum or liver HCV RNA levels. Furthermore, when patients expressing either Fas or TNFR1 were stratified according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had higher HCV viraemias. In conclusion, an HCV-mediated, in vivo blockade of hepatocyte apoptosis via the Fas- or TNFR1-dependent pathways seems unlikely

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer

Background: Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. Methods: In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. Results: Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). Conclusion: The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment

Acoustic radiation force impulse (ARFI) elastography for the noninvasive diagnosis of liver fibrosis in children

Background: Acoustic radiation force impulse (ARFI) imaging) is correlated with histopathological findings using METAVIR and semiquantitative scoring system (SSS) criteria for liver fibrosis. Objective: To compare acoustic radiation force impulse imaging with biopsy results in the evaluation of liver fibrosis in children. Materials and methods: Children with chronic liver disease and healthy children underwent acoustic radiation force impulse imaging liver measurements. ARFI gives a shear-wave velocity corresponding to tissue elasticity. In 39 children with liver disease, the values obtained were correlated with biopsy results. Receiver-operating characteristic (ROC) curves were used to determine the reliability of ARFI in estimating liver fibrosis in children. Results: ARFI mean value was 1.12 in the healthy group and 1.99 in children with chronic liver disease. ROC curves show that an ARFI cutoff of 1.34m/s is predictive of both METAVIR and SSS scores with a sensitivity of SSS > 2:0.85; METAVIR > F0:0.82. A cutoff of 2m/s yielded a sensitivity of 100% to detect SSS > 4 or METAVIR > F2. Conclusion: Acoustic radiation force impulse imaging is a reliable, noninvasive and rapid method to estimate moderate to severe liver fibrosis in children. It might prove useful to clinicians for fibrosis monitoring in children with liver disease and postpone the time of liver biops