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Biomedical subjects

J Heathcote

Publications and source records attributed to J Heathcote.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oral prostaglandin (PGE2) therapy for chronic viral hepatitis B and C.

The cytoprotective effects of prostaglandins have been utilized in the prevention of hepatitis B virus reactivation after liver transplantation. This pilot study evaluated the effects of oral prostaglandin E2 (PGE2) in chronic viral hepatitis B and C. Twenty patients with chronic hepatitis B and 20 patients with chronic hepatitis C received 4mg day-1 PGE2 for 6 months. The lymphocyte antiviral enzyme 2',5'-oligoadenylate synthetase (2',5'-OAS) and peripheral blood monocyte procoagulant activity (PCA) were measured before, during and after the treatment. Three of 20 hepatitis B and five of 20 hepatitis C patients withdrew from the study. Eight of 17 hepatitis B patients responded: in seven of these eight patients, serum alanine aminotransferase (ALT) levels normalized; loss of viral replication was sustained in all eight patients; and seroconversion from hepatitis Be antigen (HBeAg) to hepatitis Be antibody (HBeAb) positivity occurred in seven patients over the 48-week duration of this study. In 14 of the 15 hepatitis C patients, hepatitis C virus (HCV) RNA remained detectable and the serum ALT levels remained elevated. 2',5'-OAS levels and PCA values did not correlate with other markers of response to PGE2 therapy in either chronic hepatitis B or C. In summary, PGE2 was associated with sustained loss of viral replication in 47% of chronic hepatitis B patients; no beneficial effects were apparent in chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.

Administration, Oral↗
PubMed1998

Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C.

The response to interferon (IFN) therapy in patients with chronic hepatitis C is characterized by normalization of the serum alanine aminotransferase (ALT) activity during treatment, but relapse within 6 months of cessation of therapy is common. Viral characteristics, such as the genotype and viral load, may influence the patient response to IFN. The aim of this study was to examine host factors, namely the genetically determined human leucocyte antigen (HLA) class II alleles, in patients with chronic hepatitis C, and their relationship to the response to IFN therapy. Seventy white patients with chronic hepatitis C, treated with IFN-alpha for 6 months, were enrolled in the study. Serum ALT was measured at the end of treatment to assess short-term response and again 6 months post-treatment to assess sustained response. Sequence-specific primers were used in the polymerase chain reaction (PCR) to amplify genomic DNA isolated from peripheral mononuclear cells. HLA class II alleles were determined by analysis of the amplicon by gel electrophoresis and hybridization of sequence-specific oligonucleotide probes. At the end of treatment, 25 of the 70 patients (36%) had a normal ALT. By 6 months post-treatment, only six patients (9%) had a sustained normalization of ALT. The frequency of the allele DRB1*0404 was significantly higher in patients with a sustained response as compared to those lacking such a response (25.0% vs 2.3%, with a Bonferonni-corrected P-value of 0.019). There was no difference in the frequency of other class II alleles at the DRB1 and DQB1 loci in responders as compared with non-responders. Therefore, we conclude that the maintenance of a response to IFN in chronic hepatitis C may be, in part, determined by genetic factors in the host.

Alanine Transaminase↗
PubMed1998

Consensus interferon: a novel interferon for the treatment of hepatitis C.

Although alpha interferons are currently the only therapies approved for treatment of HCV infection approximately half of the treated patients do not respond to the standard regimen of IFN-alpha-2b 3 MU administered 3 times per week (tiw) for 6 to 12 months. Of those who do demonstrate a response, 50-80% will relapse within 6 months after treatment cessation. Thus, the overall response to treatment is low. This paper focuses on studies that have been conducted with a newly developed interferon, Consensus Interferon (CIFN), in the treatment of chronic Hepatitis C. This type-1 interferon links the most common occurring amino acid sequences at each position of available natural alpha interferons into one 'consensus' protein. The thus synthesized molecule shows a 10-fold higher in vitro biological activity as compared to single recombinant IFN-alpha-2b or IFN-alpha-2a, possibly due to its greater binding affinity to interferon receptors. In patients with chronic hepatitis C, CIFN 9 micrograms, three times weekly for 24 weeks, proved to be equally efficacious and as safe as IFN-alpha-2b, but compared to 3 MU IFN-alpha-2b, CIFN 9 micrograms demonstrated improved responses in patients with high baseline viral titres. Retreatment of subjects who had responded but relapsed following standard dose IFN therapy for 6 months, with 15 micrograms CIFN three times weekly for 48 weeks, resulted in a sustained virological response rate of 58%. When previous non-responders to standard IFN therapy were retreated a 13% sustained response to the higher dose of CIFN for 48 weeks was observed. The higher dose of CIFN was well-tolerated and not associated with an increase in the incidence of side-effects. CIFN proved to be an effective and safe therapy in the treatment of patients with chronic hepatitis C and the retreatment of patients who either failed previous interferon treatment or had relapsed after its cessation.

Adult↗
PubMed1998

Durability of serological remission in chronic hepatitis C treated with interferon-alpha-2B.

OBJECTIVE: We assessed the long-term effect of a course of interferon therapy on the biochemical and virological markers of Canadian patients with chronic hepatitis C. METHODS: Thirty-six patients with chronic hepatitis C were treated with a median total dose of interferon-alpha-2B of 181.0 million U (range 109.0-384.0 million U) and were followed for a median of 37.2 months (range 12.0-94.2 months) after completing treatment. All patients received an initial 16 wk of interferon at a dose of 3 million U three times weekly; this was followed by either no further interferon or by 8 wk more at doses ranging from 1.5 to 10.0 million U three times weekly. Serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were measured before interferon therapy, 6 months after treatment, and at the end of follow-up for each patient. HCV RNA was analyzed by branched DNA 1.0 assay and, if undetectable, by polymerase chain reaction. HCV genotyping was performed on serum samples. RESULTS: Five (13.6%) of the 36 patients had a sustained treatment response, defined as normal ALT and undetectable viremia 6 months after treatment. All five patients remained in serological remission to the end of their follow-up, a median of 48.2 months (range 23.0-66.2 months) after interferon therapy. Responders were similar to nonresponders in age, gender, initial ALT and serum HCV RNA levels, pretreatment histology, and total dose of interferon received. CONCLUSIONS: In patients with chronic hepatitis C, 13.6% had normal ALT and undetectable serum HCV RNA 6 months after finishing interferon therapy. These patients remained in serological remission to the end of their follow-up, 48.2 months after interferon therapy.

Adult↗
PubMed1997

Primary biliary cirrhosis, sicca complex, and dysphagia.

We investigated symptoms suggestive of swallowing problems in patients with primary biliary cirrhosis, some of whom displayed features of sicca complex. A prospective study of 95 consecutive patients with primary biliary cirrhosis was conducted at a single teaching hospital using a questionnaire administered over the telephone. Some symptoms of sicca complex (dry mouth and/or dry eyes) were found in 65 patients (68.4%). Subjective xerostomia alone was present in 45 patients (47.4%). The questionnaire revealed an increase in incidence of dysphagia in xerostomia subjects, affecting 21 of 45 patients, compared with 6 of 50 non-xerostomia patients. Multivariate logistic regression analysis showed that confounding factors such as age, obesity, cigarette smoking, and medications associated with a dry mouth could not explain these findings. Twenty-eight patients complained of hoarseness, 23 of coughing, and 14 of wheezing, all of which were significantly more frequent than in the 50 patients without xerostomia. Heartburn affected 17 xerostomia patients and 15 non-xerostomia patients, indicating no difference in frequency between these two groups, even after age, obesity, cigarette smoking, and medications associated with heartburn were considered in the multivariate analysis. Acid regurgitation, nausea, and vomiting were also similar in frequency between patients with and without xerostomia. Swallowing problems, manifested primarily as dysphagia, are common in primary biliary cirrhosis patients who have subjective xerostomia.

Adult↗
PubMed1997

The professional lives of women in gastroenterology: a Canadian comparison study with men.

Women are underrepresented in gastroenterology. A questionnaire examined the training and career experiences of female members of the Canadian Association for Gastroenterology (CAG) and their male counterparts. A pretested questionnaire was mailed to the 50 female CAG and 100 age-matched male members. Descriptive analyses were performed with the SAS statistical program. Questionnaires were returned by 38 of the women (76%) and 70 of the men (70%). All held full-time positions. Whereas 21.6% of the women respondents were pediatricians, all but 2.9% of the men had adult practices. The women were more likely to never marry (21.1% vs. 8.6% of men), and their personal income was significantly less than that of men. The men reported more problems juggling their work and private life, whereas problems with childcare and free time were reported more often by the women with children. The women perceived they had greater problems than men in pursuing an academic career, but grant support, academic rank, and administrative responsibilities were actually similar for both. Gender equality of opportunity was found in Canadian gastroenterology through a willingness on the part of women to compromise. Fewer women married and had families, and they earned less money than the men.

Adult↗
PubMed1997

The clinical expression of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is likely an autoimmune disease that destroys the interlobular bile ducts. Although the term PBC implies cirrhosis, this is not always present. The condition may be entirely silent clinically, save for the hallmark mitochondrial antibodies in serum. The clinical spectrum of PBC ranges from asymptomatic anicteric cholestasis with or without extrahepatic manifestations to severe cholestasis with decompensated cirrhosis. It is uncertain whether or not the course of this disease is universally fatal. Currently, no specific features have been identified which predict progression from asymptomatic to symptomatic disease, although once hyperbilirubinemia is present, a rising level indicates a poor prognosis. The liver-specific complications include pruritus, abdominal pain, xantholasma, and portal hypertension. The latter is often an early feature, as the portal hypertension is presinusoidal in nature and, when present, does not always reflect the presence of cirrhosis. There are many extrahepatic features of PBC, the most common being metabolic, chiefly hypothyroidism and metabolic bone disease. Other common associations are rheumatologic, renal, pulmonary, neuromuscular, and dermatologic. The non-specific yet distressing symptom of fatigue affects up to two-thirds of PBC subjects, but its etiology remains obscure.

Abdominal Pain↗
PubMed1996

Treatment of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. One-third of patients are asymptomatic and one-third of these develop symptoms within 5 years. Therapeutic regimens should be directed at the control of symptoms, prevention of complications and specific therapy aimed at controlling progression of the disease. Symptoms may be secondary to cholestasis or due to other associated diseases. The cause of pruritus secondary to cholestasis remains unknown; the anion exchange resin cholestyramine generally brings relief. In patients resistant or intolerant to this therapy, rifampin may be helpful, as well as ultraviolet light without sunblock. Liver transplantation may rarely be the only option for uncontrollable pruritus. Clinical manifestations of keratoconjunctivitis-sicca and xerostomia need constant attention to prevent corneal ulcers and dental caries. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary and the administration of the fat soluble vitamins A, D and K once hyperbilirubinaemia is present. Osteoporosis is a complication of all cholestatic liver disease. There is no satisfactory preventative therapy. It may be appropriate to give hormone replacement therapy to all post-menopausal women with PBC to reduce osteoporosis. Liver transplantation is the best option for those with fractures. Oesophageal varices may develop early in the course of PBC, non-selective beta-blocker therapy should be used as prophylaxis against variceal haemorrhage. The only specific therapy shown to cause both a biochemical and survival benefit in patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays progression, but does not result in a cure of this disease. Currently, liver transplantation is the only definitive treatment available for end-stage disease.

Female↗