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Biomedical subjects

Z D Goodman

Publications and source records attributed to Z D Goodman.

At least 19 recordsLinked to original sources
PubMed2001

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

BACKGROUND: A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin. METHODS: 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. FINDINGS: The SVR rate was significantly higher (p=0.01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. INTERPRETATION: In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

Adult↗
PubMed2001

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B.

BACKGROUND: Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha-SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis. AIM: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. METHODS: Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine (n=47) or placebo (n=33) were studied. alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. RESULTS: Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression (1.06+/-0.23 vs. 0.58+/-0.11, pre vs. post, P<0.05). Placebo recipients had increased levels of alpha-SMA (0.82+/-0.14 vs. 1.32+/-0.21, P<0.05). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. CONCLUSIONS: Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents.

Actins↗
PubMed2001

Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study.

Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera. All-cause mortality was 67% among 222 hepatitis C-related cases and 65% among 377 controls (P = NS). Liver-related mortality was 4.1% and 1.3%, respectively (P =.05). Of 129 living persons with previously diagnosed transfusion-associated hepatitis (TAH), 90 (70%) had proven TAH-C, and 39 (30%), non-A-G hepatitis. Follow-up of the 90 TAH-C cases revealed viremia with chronic hepatitis in 38%, viremia without chronic hepatitis in 39%, anti-HCV without viremia in 17%, and no residual HCV markers in 7%. Thirty-five percent of 20 TAH-C patients biopsied for biochemically defined chronic hepatitis displayed cirrhosis, representing 17% of all those originally HCV-infected. Clinically evident liver disease was observed in 86% with cirrhosis but in only 23% with chronic hepatitis alone. Thirty percent of non-A, non-B hepatitis cases were unrelated to hepatitis viruses A,B,C, and G, suggesting another unidentified agent. In conclusion, all-cause mortality approximately 25 years after acute TAH-C is high but is no different between cases and controls. Liver-related mortality attributable to chronic hepatitis C, though low (<3%), is significantly higher among the cases. Among living patients originally HCV-infected, 23% have spontaneously lost HCV RNA.

Aged↗
PubMed2001

A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.

Adult↗
PubMed2001

Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens.

BACKGROUND: Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene. METHODS AND RESULTS: We investigated the utility of HFE gene sequence analysis in the diagnosis of HH in 61 prospectively accrued formalin-fixed, paraffin-embedded liver biopsy specimens with clinical or histologic features suggestive of HH. Mutations in codons 63 or 282 of the HFE gene were identified by direct sequencing; in 21 of these samples, quantitative hepatic iron testing was also performed. Changes characteristic of HH were present in 16 (26%) of the cases, and 54% of the cases showed HFE gene mutations. The most common alteration was homozygous mutation of codon 282 (11 cases, 18%), followed by the combined 63 + 282 heterozygous mutation (3 cases, 5%). Two cases (3%) showed biallelic mutation of codon 63. The other 28 cases (46%) showed no sequence abnormalities. Weak iron staining did not exclude HH; intense staining did not reliably predict HH. CONCLUSION: When HH is clinically and/or histologically suspected, HFE gene sequencing of formalin-fixed, paraffin-embedded liver biopsy specimens is a rapid and cost-effective approach to genotypic diagnosis of HH.

Age Factors↗
PubMed2001

Eosinophilic granuloma of the liver: a characteristic lesion with relationship to visceral larva migrans.

Children with the clinical syndrome of visceral larva migrans as a result of Toxocara species have typical lesions in the liver and other viscera, consisting of palisading granulomas that contain numerous eosinophils and often Charcot-Leyden crystals; recognizable parasites are uncommon. Similar eosinophilic granulomas that are found incidentally in adults often cause diagnostic problems. To define better the clinical, laboratory, and pathologic features of these lesions, we reviewed 43 cases of hepatic eosinophilic granuloma (excluding cases of Langerhans' cell histiocytosis) collected in the files of the AFIP over a period of 31 years. The eosinophilic granulomas were found in patients of all ages (range 12 months to 77 years); 30% were younger than 20 years. There were 26 male and 17 female patients. Most patients (26 of 43; 60%) were asymptomatic, and the lesions were discovered incidentally. Others had fever (20%) or abdominal pain (20%). The granulomas were typically multiple (61%), with central necrosis surrounded by a mixed inflammatory infiltrate with numerous eosinophils and variable numbers of neutrophils. lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells. Charcot-Leyden crystals were present in 19 cases (44%). Remnants of parasites (eight Toxocara sp., two Capillaria sp.) were identified in the tissue in 10 patients. There was a positive serologic test for Toxocara sp. in five additional cases. Immunohistochemical staining using polyclonal antiserum against Toxocara canis larvae demonstrated positivity in macrophages in eight of 13 cases tested. We conclude that identification of an eosinophilic granuloma in the liver should suggest the diagnosis of visceral larva migrans and prompt a search for the causative organism with serial sectioning of the block and serologic tests for Toxocara and other causative parasites.

Adolescent↗
PubMed2001

Hepatic decompensation associated with lamivudine: a case report and review of lamivudine-induced hepatotoxicity.

We report a case of a 62-yr-old man with chronic hepatitis B virus (HBV)-related cirrhosis who developed hepatic decompensation after being started on lamivudine requiring liver transplantation. Decompensated liver disease while on lamivudine has been previously reported on two occasions, both HIV coinfected patients on a combination of nucleoside analogues. Our patient is alive and well nearly 2 yr after successful liver transplantation.

Hepatitis B, Chronic↗
PubMed2000

Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults.

The perivascular epithelioid cell family of tumors (PEComas), defined by their co-expression of melanocytic and muscle markers, includes angiomyolipoma, lymphangioleiomyoma, and clear cell "sugar" tumors of the lung, pancreas, and uterus. We present seven cases of a unique and previously unrecognized tumor of children and young adults, which represents a new addition to the PEComa group of tumors. Culled from three institutions over a 50-year period, all cases occurred in or immediately adjacent to the ligamentum teres and falciform ligament. Six patients were female and one male; their ages ranged from 3 to 21 years (median, 11 yrs). Tumor sizes ranged from 5 to 20 cm (median, 8 cm). All cases consisted of clear to faintly eosinophilic spindled cells arranged in fascicular and nested patterns. The cells had small but distinct nucleoli and low mitotic activity. Immunohistochemically, all cases were positive with antibodies to gp100 protein (HMB-45) and negative for S-100 protein. In three of the seven cases studied immunohistochemically, the tumors expressed smooth muscle actin, melan-A, microphthalmia transcription factor (MiTF), and myosin, but not desmin. No expression of the TSC2 gene product, tuberin, was seen in three cases. One case studied cytogenetically disclosed a t(3;10). Follow-up data, available in six of seven cases (median duration, 18 mos), showed five patients to be free of disease and one to have a radiographically presumed lung metastasis. We think these tumors comprise a new entity for which we propose the term "clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres." The differential diagnosis of these tumors includes clear cell sarcoma of tendons and aponeuroses, leiomyosarcoma, and angiomyolipoma.

Abdominal Neoplasms↗
PubMed1999

Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin that occurs in the liver and other organs; its etiology is unknown. METHODS: The authors analyzed the clinicopathologic and immunohistochemical features of 137 patients with EHE of the liver in an attempt to identify features that might predict tumor behavior. To their knowledge, this article represents the largest series reported from one institution. RESULTS: Patients were ages 12-86 years; 84 (61%) were females and 53 (39%) were males. They presented with nonspecific symptoms such as right upper quadrant pain or weight loss. Macroscopically, the tumors usually were multiple. They typically were white, firm to hard, and ranged in size from 0.2-14 cm. Histologically, the tumors were comprised of dendritic and epithelioid cells that often contained vacuoles representing intracellular lumina. The stroma was fibrous, with myxohyaline areas. Immunohistochemically, all tumors were positive for at least one endothelial marker (factor VIII-related antigen [FVIII-RAg], CD34, and/or CD31). Treatment modalities included hepatic resection or transplantation. Although the metastatic rate in this series was 27%, the prognosis is considered much more favorable than that of other hepatic malignancies. Twenty-six patients (43%) survived > or = 5 years; 2 patients were alive and well at last follow-up after 23 and 27 years, respectively. Twenty-six of 60 patients (43%) died of their disease, 1 of whom died 28 years after discovery of her tumor. In an attempt to predict behavior of the tumor, several histologic parameters were evaluated using univariate analysis. No significant correlation was found with mitoses, Glisson's capsule infiltration, or nuclear atypia. High cellularity was significantly correlated with a poor clinical outcome (P = 0.00012), whereas the association with tumor necrosis approached significance (P = 0.057). CONCLUSIONS: EHE is a very rare clinical entity. The key to diagnosis is the demonstration of cells containing FVIII-RAg. The histology of the tumor, including nuclear pleomorphism and the mitotic count, are of no value in predicting clinical outcome. High cellularity most likely is the most significant parameter predicting an unfavorable prognosis in EHE because mitotic counts often are quite low in both low grade and aggressive tumors. Further studies are needed to identify the factors responsible for the apparent dissociation between the clinical behavior and biologic characteristics of this tumor.

Adolescent↗
PubMed1999

Ciliated hepatic foregut cyst: a study of six cases and review of the literature.

Ciliated hepatic foregut cyst (CHFC) is a rare, benign, solitary cyst consisting of ciliated pseudostratified columnar epithelium, subepithelial connective tissue, a smooth muscle layer, and an outer fibrous capsule. We studied six previously unreported cases of CHFC and 50 cases from the literature. The literature search revealed that Friedreich first described the lesion in 1857 and hypothesized its congenital origin. The cyst generally is found incidentally on radiologic imaging or during surgical exploration, although one case presented with portal vein compression. It occurs more frequently in men and is found most commonly in the medial segment of the left hepatic lobe, unlike most other solitary cysts that show a female predominance and greater occurrence in the right hepatic lobe. Two of the 56 cases were multilocular. There has been an increase in the number of reports of CHFC during the past 15 years. This may reflect the increased availability and use of various radiologic imaging modalities. A large number of cases have been reported in the Japanese population, but the significance of this is unclear. CHFC should be considered in the differential diagnosis of other solitary liver cysts, including simple cysts, hepatobiliary cystadenomas, and parasitic cysts.

Adenoma, Bile Duct↗
PubMed1999

Squamous cell carcinoma arising in a ciliated hepatic foregut cyst.

Ciliated hepatic foregut cysts are rare congenital lesions derived from the embryologic foregut. They are considered benign, and a review of 64 published cases revealed no instances of malignant transformation. We report a case of squamous cell carcinoma arising in a ciliated hepatic foregut cyst in a 51-year-old man. The tumor was found during a routine cholecystectomy and involved the adjacent mesentery and duodenal wall. There was histologic evidence of perineural and perivascular involvement. Despite an en bloc resection of the tumor and contiguous areas of gross involvement, the patient died 2 months later. Although aspiration of cyst contents is an accepted treatment for asymptomatic lesions, this case suggests that most ciliated hepatic foregut cysts should be excised, especially when radiologic studies yield equivocal results.

Carcinoma, Squamous Cell↗
PubMed1999

Liver involvement in Langerhans' cell histiocytosis: a study of nine cases.

Nine cases of Langerhans' cell histiocytosis (LCH) of the liver are presented. Five of the patients had liver involvement only. Other organ systems, notably the lymph nodes and skin, were involved in the other four patients. Four of the patients had sclerosing biliary disease with infiltration of the bile ducts by Langerhans' cells, whereas in two other patients, the biliary sclerosis was not associated with direct hepatic involvement by Langerhans' cells. Histologically, the lesions were composed of focal aggregates of Langerhans' cells in a polymorphous background of mature eosinophils, lymphocytes, neutrophils, and plasma cells. LCH encompasses a syndrome that has a broad range of clinical presentations and that might involve the liver solely as tumor-like lesions or cystic lesions, or as part of systemic disease. Even when Langerhans' cells are not demonstrable, sclerosing cholangitis can be seen in LCH.

Antigens, CD1↗
PubMed1998

Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.

BACKGROUND: Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy. CONCLUSIONS: In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone.

Adult↗
PubMed1998

Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial.

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.

Adult↗
PubMed1998

Solitary fibrous tumor of the liver: a clinicopathologic and immunohistochemical study of nine cases.

Nine cases of primary solitary fibrous tumors of the liver are presented. The patients are 7 women and 2 men between the ages of 32 and 83 years (mean, 57.5 years). Clinically, palpable masses were detected during physical examination in five patients. Two patients presented with symptoms of cholecystitis, one with hematuria, one with periumbilical pain, and one with hypoglycemia. One patient was found to have an abdominal mass during follow-up evaluation for colonic carcinoma, whereas in one patient the tumor was an incidental finding at autopsy. Two patients were asymptomatic, and the tumor masses were detected during a routine physical examination. Grossly, the tumors varied in size from 2 to more than 20 cm in greatest dimension and were described as firm, white-to-gray, well or ill defined. Eight tumors were described as intraparenchymal lesions, two were grossly necrotic, and one tumor was attached by a pedicle to the liver capsule without infiltration into the liver parenchyma. Histologically, most of the tumors had a bland appearance with the classic short storiform (so-called patternless) pattern and absence of cellular atypia, mitoses and/or necrosis. However, in two cases, there was marked cellular atypia and mitotic figures varying from 2 to 4 mitoses per 10 high power field (hpf). Immunohistochemically, all the tumors showed a strong positive reaction against antibodies for CD-34 and vimentin. Follow-up information showed that two patients died within days of postsurgical resection of the tumor, whereas one was alive and well 1 year after initial diagnosis. No follow-up information was available for the other five patients. The cases herein presented highlight the ubiquitous distribution of this neoplasm and the similar clinical and histopathological features to those observed in serosal surfaces. Solitary fibrous tumors of the liver, although rare, need to be considered in the differential diagnosis of mesenchymal lesions of the liver.

Adult↗
PubMed1998

A simple and rapid stain for copper in liver tissue.

We report a modified copper stain that can be completed in 2 hours, rather than overnight, which is required for other stains. This is useful in the diagnosis of chronic cholestatic syndromes, Wilson's disease, Indian childhood cirrhosis, and other conditions associated with copper retention.

Alum Compounds↗
PubMed1998

Absence of human herpesvirus 8 DNA sequences in vascular tumors of the liver.

Kaposi's sarcoma-associated herpes virus (KSHV), also designated human herpesvirus 8 (HHV8), has been detected consistently in Kaposi's sarcoma, body cavity lymphoma and multicentric Castleman's disease, both in human immunodeficiency virus (HIV)-positive and -negative patients. Identification of KSHV/HHV8 DNA sequences in various benign and malignant vascular tumors in HIV-negative patients was reported in one study, but was not confirmed in several other studies. The vascular lesions, other than Kaposi's sarcoma, in which sequences could not be detected have included malignant vascular tumors of serous membranes, infantile capillary hemangiomas, and several benign and malignant vascular tumors of the spleen. We studied 30 primary benign and malignant vascular tumors of the liver; KSHV/HHV8 DNA sequences could not be detected in any. We conclude that this virus plays no role in the etiology of vascular tumors of the liver.

Adult↗