Appendiceal adenocarcinoma with ovarian metastases in the third trimester of pregnancy.
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Adenocarcinoma↗
Biomedical subjects
R D Goldin
Publications and source records attributed to R D Goldin.
Subcellular localisation of NS3 in HCV-infected hepatocytes.
Hepatitis C virus (HCV) NS3 is a multifunctional protein with both protease and helicase activities and has been shown to interact with host cell proteins. It is shown that NS3 is present in the hepatocytes from patients with chronic HCV infection by using anti-NS3 antisera. NS3 is detectable in approximately 4% of the hepatocytes from these patients. In most infected cells, NS3 is present in the cytoplasm; however, in a minority of HCV-infected cells, both the cytoplasm and the nucleus or the nucleus on its own are positive for NS3. The presence of NS3 in the nuclei of hepatocytes in chronically infected patients indicates that the protein may play a role other than in virus replication, such as in persistence of HCV infection.
Blotting, Western↗
Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group.
This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P <.001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (>/=2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B.
Adolescent↗
Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis.
The effects of chronic hepatitis C virus (HCV) infection, in the absence of cirrhosis, on patients' quality of life was assessed using the short form 36 (SF36) symptomatology questionnaire. Patients with chronic hepatitis C were polysymptomatic and had significant reductions in their SF36 scores for all of the modalities tested. Patients with chronic hepatitis B virus (HBV) infection showed a reduction in the SF36 scores that assessed mental functions, but they had no decrease in the scores that measured physical symptoms, indicating that the symptoms associated with chronic HCV infection are qualitatively different from those associated with chronic HBV infection. Patients with chronic HCV infection who had used intravenous drugs in the past had the greatest impairment in quality-of-life scores, but the reduction in quality-of-life scores was still found in patients who had never used drugs. The reduction in quality of life could not be attributed to the degree of liver inflammation or to the mode of acquisition of the infection. Hence, chronic infection with HCV per se gives rise to physical symptoms that reduce the quality of life of infected patients.
Adult↗
Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: results of an international randomized controlled trial. Clinical Advisory Group for the Hepatitis C Comparative Study.
The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-alpha) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN-alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-alpha n1 were HCV RNA negative at week 72 compared with patients treated with IFN-alpha2b (P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN-alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha n1 and IFN-alpha2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN-alpha treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.
Adolescent↗
Hepatitis D virus antigen in HBsAg positive chronic liver disease in Nigeria.
Hepatitis B virus (HBV) is strongly associated with an aggressive type of chronic active liver disease (CALD) and hepatocellular carcinoma, which tend to present in the relatively young, in sub-Saharan Africa. It is known that co-existent infection with HDV tends to aggravate the course of HBV-associated liver disease. This study was carried out to determine the sero-prevalence of hepatitis D virus (HDV) among thirty one consecutive southwestern Nigerians with HBsAg-positive, HCV antibody-negative chronic liver disease. Alongside, we tested for HBsAg and the HDV antigen in fifty randomly selected sera each from blood donors and university freshmen undergoing pre-admission medical tests and who had no clinical evidence of liver disease. The HDV antigen (HDVAg) was found in the sera of two of 31 (6.5%) patients. Among the blood donors and university freshmen, HBsAg prevalence was twelve and eight per cent respectively, while HDVAg was present in none. In addition, liver biopsies of 28 other patients were stained for HDVAg. None of these was positive. These findings show that HDV prevalence is low in our community, and suggest that the virus might play only a minor role in the pathogenesis of HBsAg-associated chronic liver disease among our patients. A review of reports on the epidemiology of HDV in sub-Saharan Africa shows a rather complicated pattern that makes its impact on HBsAg-associated CALD difficult to assess. More studies designed to elucidate this pattern of HDV epidemiology are called for.
Blood Donors↗
Management of chronic hepatitis C: clinical audit of biopsy based management algorithm.
OBJECTIVE: To assess the attendance, outcome, compliance with treatment, and response to interferon alfa in patients with chronic hepatitis C who attended during 1995 and were treated according to a biopsy based algorithm. DESIGN: Retrospective audit of all patients with chronic hepatitis C attending outpatient clinics over one year. SETTING: The liver unit at a London teaching hospital. SUBJECTS: 255 patients with chronic hepatitis C. MAIN OUTCOME MEASURES: Patient survival, attendance, and compliance with diagnostic and therapeutic regimens. Response to interferon alfa treatment, based on loss of viraemia three months after cessation of treatment. RESULTS: A large proportion of patients (39%) with newly diagnosed chronic hepatitis C infection do not want to undergo further investigation. Of those patients who do attend for further treatment, a large proportion with severe hepatic fibrosis (42%) do not want to undergo currently available treatment. The response rate to interferon (21%) in treated patients was similar to that previously reported in a trial setting. There was no significant difference in response rates in patients with or without severe fibrosis not amounting to cirrhosis. In patients with cirrhosis there was a high incidence of hepatocellular carcinoma (18%) over a follow up period of 20 months. CONCLUSION: Current strategies aimed at investigating and treating patients with chronic hepatitis C are not acceptable to a large proportion of patients. Many patients with cirrhosis related to hepatitis C infection develop hepatic neoplasms, and management strategies to deal with this problem are urgently required.
Adult↗
Diagnosis of biliary ductopaenia.
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Autoimmune Diseases↗
Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis C.
Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.
Adult↗
The relationship of histology to genotype in chronic HCV infection.
The histological description of chronic hepatitis is undergoing considerable change at present. It has become important to define chronic hepatitis aetiologically and then define levels of necro-inflammatory change (grade) and fibrosis (stage). The aim of this study was to compare the ability of different histological scoring systems to detect differences in the pathological changes associated with infection with the different HCV genotypes that are known to have different natural histories. The histological appearances of liver biopsies from 29 HCV infected patients were compared by the Knodell histological activity index (HAI), modified histological activity index and the Scheuer histological scoring system. HCV genotyping was performed for each patient by sequence analysis of the 5' non-coding region. The histological appearances from HCV 1 infected patients showed a tendency towards more active necro-inflammatory changes when compared with those from HCV 2 or 3 infected patients. The levels of fibrosis were similar for all genotypes. The modified HAI and Scheuer scoring systems detected differences, not revealed by the Knodell system, in the types of inflammatory pathology produced by the different genotypes of HCV. In particular these scoring systems noted significant differences in the component scores of inflammation, in addition to the total inflammatory scores. In conclusion, the recently introduced scoring systems were able to detect differences in liver pathology produced by infection of similar duration with different viral genotypes. As genotype is considered an important determinant of disease progression and response to anti-viral therapy, it is likely that those scoring systems correlating with genotype will yield more useful histological information than those that do not.
Adult↗
A solitary benign lymphoid polyp of the rectum in a 51 year old woman.
A 51 year old woman presented with rectal bleeding from a mass lying just above the dentate line. Multiple biopsies were taken before the diagnosis of a benign lymphoid polyp was made. This is a rare condition that more commonly presents in children and poses a diagnostic challenge.
Diagnosis, Differential↗
Role of macrophages in acetaminophen (paracetamol)-induced hepatotoxicity.
Research into the pathogenesis of acetaminophen (paracetamol)-induced hepatotoxicity has concentrated on the generation of toxic metabolites by the hepatocytes. It has, however, recently been shown that human macrophages cultured with acetaminophen secrete increased quantities of tumour necrosis factor (TNF). This study examines whether macrophages have a direct role in acetaminophen toxicity, using a mouse model in which it is possible to eliminate more that 99 per cent of hepatic macrophages by previously injecting liposomes containing dichloromethylene disphosphonate (DMDP). Acetaminophen-induced liver damage was assessed biochemically and histologically. It was shown that the liver damage occurring 0.5, 1, and 2 h after an intraperitoneal injection of acetaminophen was significantly less in mice previously injected with liposomes containing DMDP than in previously untreated mice, or mice previously injected with empty liposomes. By 4 h there was no difference between the groups. We conclude that macrophages play an early and probably a direct role in mediating the liver damage due to acetaminophen. This is consistent with the role that macrophages have been shown to play in the pathogenesis of alcohol-induced liver damage.
Acetaminophen↗
Intra-observer and inter-observer variation in the histopathological assessment of chronic viral hepatitis.
BACKGROUND/AIMS: The way in which liver biopsies showing chronic hepatitis are reported is undergoing re-evaluation. A related question is how the inflammatory and fibrotic changes in these liver biopsies can be semi-quantitatively assessed so that comparisons can be made between groups of patients and the effect of treatment on disease progression studied. METHODS: We have carried out a blinded trial in which 20 cases of chronic viral hepatitis were assessed by five histopathologists, using the Knodell and Scheuer scoring systems (two of the most commonly used systems), on two separate occasions. The results were analysed using Kappa statistics, and also by seeing for how many slides the pathologists showed no significant disagreement. RESULTS: While both systems produced good inter- and intra-observer variation when fibrosis was assessed the Scheuer system produced slightly higher Kappa values. The Scheuer system produced considerably better agreement when the severity of inflammation was examined. A multirater kappa analysis confirmed that both systems showed better agreement for fibrosis scores than for inflammation scores. CONCLUSION: We conclude that, while both systems produced reasonable agreement, this was greater using the Scheuer system. When any new scoring system is being developed, the question of reproducibility needs active consideration.
Chronic Disease↗
Granulomas and hepatitis C.
Hepatitis C (HCV) is associated with a number of characteristic histological features. A recent paper has identified an increased frequency of granulomas in resection specimens from cases of HCV. We have carried out a retrospective study of 155 cases of HCV to assess the frequency of granulomas in biopsy specimens. We had two control groups: 151 cases of hepatitis B (HBV) and 129 cases of alcohol induced liver disease. Granulomas were found in 14 cases of HCV (10%), three cases of HBV (2%) and three cases of alcohol induced liver disease (2%). Granulomas were significantly commoner in cases of HCV than in the other two groups. Of the 14 cases of HCV, the granulomas could be ascribed to another cause in seven cases. When the analysis was carried out, excluding those granulomas which could be ascribed to another cause, they were still significantly commoner in cases of HCV. We conclude that granulomas are more frequent in HCV but that in half of cases in which they are found another cause can be identified. This means that if granulomas are seen in association with hepatitis C another aetiology should be sought before ascribing them to HCV.
Granuloma↗
The expression of hepatitis B virus polymerase in hepatocytes during chronic HBV infection.
A recombinant protein corresponding to part of the amino-terminal domain of hepatitis B virus (HBV) polymerase was expressed in Escherichia coli. Antisera raised against this protein stained hepatocytes, from human liver biopsies, predominantly in the nucleus but some cytoplasmic staining was also observed. No staining was observed in hepatocytes from uninfected patients. Liver biopsies, taken from patients who were infected with human immunodeficiency virus (HIV) as well as HBV showed more intense staining with these antisera than that seen in patients who were infected with HBV alone. The staining pattern suggests that either the whole HBV polymerase protein, or a portion encoding the amino-terminal domain, is translocated to the nucleus. This event may be an important early step in replication of the HBV genome.
AIDS-Related Opportunistic Infections↗
Hepatitis C and bile duct loss.
AIM: To assess whether bile duct loss is associated with the bile duct damage induced by chronic hepatitis C. METHODS: Sections were examined from 171 liver biopsy specimens from patients with chronic hepatitis C, 98 biopsy specimens from patients with chronic hepatitis B, 25 postmortem specimens from patients with no evidence of liver disease, and 23 patients who underwent protocol liver biopsy at the time of cholecystectomy. RESULTS: The bile duct:portal tract ratio for the hepatitis C group was 0.89, for the hepatitis B group was 0.93 and for the two control groups was 0.96 and 0.90, respectively. The ratio was lower in the hepatitis C group than in the other three. In no case of chronic hepatitis C was the ratio less than 0.60. In the hepatitis C group greater bile duct loss was seen in cirrhotic patients. CONCLUSIONS: Hepatitis C is associated with bile duct loss and this was related to the stage of the disease. However, in the cases studied this did not reach what is generally considered to be significant (that is, greater than 50% of portal tracts lacking bile ducts). This does not preclude a contributory effect of hepatitis C to bile duct loss in the presence of other risk factors, especially in liver transplant recipients.
Bile Duct Diseases↗
Fatal haemorrhage following liver biopsy in patients with HIV infection.
A retrospective review of all 248 liver biopsies performed in patients with HIV infection at two referral centres in London over a 12 year period revealed five cases of major bleeding following biopsy, with four deaths. The risk of major bleeding was 2.0%, and mortality was 1.6% following liver biopsy. The risk of bleeding as much higher than in published series of biopsies done in patients without HIV infection, owing in part to the high prevalence of thrombocytopaenia and clotting abnormalities in patients with HIV infection. HIV infection per se may also increase the risk of bleeding following liver biopsy.
Adult↗
Fibrosing cholestatic hepatitis in a renal transplant recipient associated with the hepatitis B virus precore mutant.
A patient with evidence of chronic infection with hepatitis B virus (seropositive for hepatitis B surface antigen, and with antibody to hepatitis B e antigen) underwent renal transplantation, which subsequently failed. The patient developed abnormal liver function tests and 8 months after the removal of the transplanted kidney, hepatitis B virus DNA was detected in the serum in the absence of hepatitis B e antigen. Liver biopsy revealed the presence of fibrosing cholestatic hepatitis. Sequence analysis of the serum hepatitis B virus DNA showed the presence of the pre-core mutant. This case shows that fibrosing cholestatic hepatitis can occur outside the setting of liver transplantation, and coincided with the development of the pre-core mutant of hepatitis B virus.
Base Sequence↗