Progression of fibrosis during chronic hepatitis C is associated with rapid virus evolution.

Hepatic fibrosis is the primary mediator of disease due to chronic infection with hepatitis C virus (HCV). HCV exists as a quasispecies in each infected individual, and longitudinal viral sequence changes may reveal viral dynamics and the selection pressures applied by the host immune system. Thus, we hypothesized that patterns of sequence change might reveal the immunopathogenesis of fibrosis progression.

Intraarterial therapy with a new potent inhibitor of tumor metabolism (3-bromopyruvate): identification of therapeutic dose and method of injection in an animal model of liver cancer.

Purpose: A potent new adenosine triphosphate inhibitor--3-bromopyruvate (3-BrPA)--has been shown to have antitumor effects when injected intraarterially in the hepatic artery of rabbits with VX-2 tumors. The authors performed a stepwise study in rabbits to determine the therapeutic dose and method of delivery of 3-BrPA.

Materials And Methods: White New Zealand rabbits with VX-2 tumors were used for this study.

Differences in characteristics of patients with and without known risk factors for hepatocellular carcinoma in the United States.

Aim: To examine the clinical characteristics of a subgroup of patients with hepatocellular carcinoma (HCC) and compare them to those with known risk factors.

Methods: We used the HCC database of 306 patients seen at our institution from January 1, 1995 to December 31, 2001. Of the 306 patients, 63 (20%, group 1) had no known risk factors (hepatitis C virus, hepatitis B virus, alcohol, hemochromatosis or cirrhosis from any cause) and 243 (group 2) had one or more risk factors.

Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: potential implication for HIV transmission.

Background: Many sexual lubricants are hyperosmolar. Hyperosmolar enemas induce epithelial damage, and enema use has been associated with an increased risk of HIV infection. To inform the development of rectal microbicide formulation, we evaluated the effects of hyperosmolar gels on the rectal mucosa.

Use of T-cell antibodies for donor dosaging in a canine model of in utero hematopoietic stem cell transplantation.

Aim: Microchimerism following canine in utero hematopoietic stem cell transplantation (IUHSCT) development of T-cell dosing regimens.

Objective: To investigate the use of anti-T-cell antibodies for cell dosing of the donor graft in a canine model of IUHSCT.

Study Design: Canine IUHSCT was performed by ultrasound-guided intraperitoneal injection in days 35-38 of fetal canines with CD34(+) cells at doses of 4.

Limited effectiveness of antiviral treatment for hepatitis C in an urban HIV clinic.

Objective: To evaluate predictors and trends of referral for hepatitis C virus (HCV) care, clinic attendance and treatment in an urban HIV clinic.

Design And Methods: A retrospective cohort analysis in which 845 of 1318 co-infected adults who attended the Johns Hopkins HIV clinic between 1998 and 2003 after an on-site viral hepatitis clinic was opened, attended regularly (>/= 1 visit/year for >/= 2 years). Logistic regression was used to examine predictors of referral.

Atrophic autoimmune pangastritis: A distinctive form of antral and fundic gastritis associated with systemic autoimmune disease.

The 2 major recognized forms of atrophic gastritis are autoimmune and environmental atrophic gastritis. These differ in their topographical distribution in the stomach, histologic features, and etiology. Autoimmune atrophic gastritis results from immune-mediated destruction of specialized oxyntic glands, is restricted to the body and fundus, and shows characteristic neuroendocrine hyperplasia.

Sirolimus monotherapy versus sirolimus in combination with steroids and/or MMF for immunosuppression after liver transplantation.

Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolate mofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 +/- 10 months.

Hepatitis C and hepatitis B nucleic acids are present in intrahepatic cholangiocarcinomas from the United States.

Intrahepatic cholangiocarcinomas (IHCs) are rare in the United States, but the prevalence is steadily increasing and risk factors are poorly understood. Tissues were obtained at the time of surgical resection, and 11 cases of IHC were retrospectively studied for the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA. Hemi-nested and real-time polymerase chain reaction assays were used to detect HBV DNA, and nested reverse transcriptase-polymerase chain reaction was used to detect HCV RNA.

EGFR is phosphorylated at Ty845 in hepatocellular carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of hepatocellular carcinomas. Recent studies of EGFR inhibitors to treat hepatocellular carcinoma have been encouraging and better understanding of EGFR signaling may lead to more effective strategies for inhibiting this key pathway. The EGFR can be phosphorylated at different tyrosine sites, leading to subsequent activation of different pathways.

Glycogen pseudoground glass change in hepatocytes.

Ground glass cytoplasmic change in hepatocytes is typically associated with chronic hepatitis B infection. We report 12 cases of glycogen pseudoground glass change that closely mimics hepatitis B inclusions. Nine individuals were immunosuppressed secondary to liver or kidney transplant (N=3), bone marrow transplant (N=2), HIV infection (N=2), kidney dialysis (N=1), or chronic inflammatory bowel disease (N=1).

Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients.

Purpose: Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form of chronic liver disease. Although NAFLD is known to be associated with obesity and some comorbid conditions, less is known about the severity of NAFLD among different racial groups.

Methods: We prospectively studied 237 consecutive morbidly obese patients presenting for bariatric surgery.

Tuberculosis-associated haemophagocytic syndrome.

Haemophagocytic syndrome is a disorder characterised by fevers, lymphadenopathy, hepatosplenomegaly, cytopenias, and hyperferritinaemia due to dysregulated activation and proliferation of macrophages, leading to uncontrolled phagocytosis of platelets, erythrocytes, lymphocytes, and their haematopoietic precursors throughout the reticuloendothelial system. Primary or familial haemophagocytic syndrome appears to have a genetic aetiology, whereas secondary haemophagocytic syndrome may be associated with malignancy, autoimmune disease, or infection. Epstein-Barr virus is the most common infectious aetiology implicated in haemophagocytic syndrome, but the syndrome has been associated with a variety of other viral, bacterial, and parasitic pathogens.

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice.

Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using liver-specific targeted disruption of tumor suppressors SMAD4 and PTEN.

Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery.

New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer.

Background: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery.

Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus.

Reported are the clinical and pathologic features of glycogenic hepatopathy, a pathologic overloading of hepatocytes with glycogen that is associated with poorly controlled diabetes mellitus. Fourteen cases were studied by stains, including hematoxylin and eosin, trichrome, periodic acid-Schiff, and periodic acid-Schiff with diastase. Ultrastructural analysis was performed in 2 cases.

Progression of liver fibrosis among injection drug users with chronic hepatitis C.

Although most hepatitis C virus (HCV) infections are acquired by injection drug use, prospective data on the progression of liver fibrosis are sparse. Baseline liver biopsies were obtained (1996-1998) on a random sample of 210 out of 1667 HCV-positive injection drug users (IDUs). Subjects were followed biannually, with a second biopsy offered to those eligible.

Effects of the type of embolization particles on carboplatin concentration in liver tumors after transcatheter arterial chemoembolization in a rabbit model of liver cancer.

Purpose: To study the effect of particle type used during transarterial hepatic chemoembolization (TACE) on carboplatin concentration after TACE in an animal model of liver cancer (VX2) and to determine the concentration of carboplatin within tumor, liver, and plasma.

Materials And Methods: The VX2 tumors were grown in the livers of 23 rabbits. Carboplatin (5 mg/kg) was selected because of its known potency against VX2 tumor.

Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.

Hedgehog (Hh) pathway activation promotes tumors in several endodermally derived tissues, but its role in the pathogenesis of hepatocellular carcinoma (HCC) is unknown. Although normal hepatocytes lack Hh signaling, activation of the Hh pathway in endodermal progenitors is required for liver development. Thus, we hypothesized that hepatocarcinogenesis may involve regulation of Hh signaling.

Role for hedgehog signaling in hepatic stellate cell activation and viability.

Hepatic stellate cells (HSC) have a complex phenotype that includes both neural and myofibroblastic features. The Hedgehog (Hh) pathway has been shown to direct the fate of neural and myofibroblastic cells during embryogenesis and during tissue remodeling in adults. Therefore, we hypothesized that Hh signaling may regulate the fate of HSC in adults.

Primary liver carcinoma arising in people younger than 30 years.

Primary liver carcinomas in children and young adults are uncommon and poorly described. We examined primary liver carcinomas in people younger than 30 years and performed immunostains for markers of biliary (cytokeratin [CK] 7, CK19, CD56) and hepatocellular (HepPar) differentiation. We found 23 primary liver carcinomas were found: 13 hepatocellular carcinomas (HCCs), 9 fibrolamellar carcinomas (FLCs), and 1 cholangiocarcinoma.

Inflammatory pseudotumor of the liver.

Inflammatory pseudotumor of the liver (IPL) is a rare benign neoplasm. It often masquerades as a malignancy, either primary or metastatic. We describe the case of a 71-year-old man who presented with fever and malaise.

De novo hepatocellular carcinoma in a liver allograft associated with recurrent hepatitis B.

Recurrent hepatocellular carcinoma is well described following liver transplantation. However, de novo hepatocellular carcinoma in the allograft is rare. We describe the clinical and pathological features of a case of de novo hepatocellular carcinoma arising in a cirrhotic allograft 9 years following transplantation for chronic hepatitis B.

Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials.