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S Sachithanandan

Publications and source records attributed to S Sachithanandan.

9 recordsLinked to original sources

Chronic HCV histology is predictable from HCV RNA and IgM anti HCV results.

The aim of this study was to determine if knowledge of both the serum HCV RNA and serum anti core IgM antibody status enabled one to predict the histological severity in chronic hepatitis C. We studied 45 female patients with chronic hepatitis C infection. The presence or absence of IgM antibodies to HCV and HCV RNA by PCR in each patient's serum was determined. Liver biopsies performed were scored according to a modified Desmet's histological activity index. Negative HCV RNA patients had least histological change. HCV RNA positive patients who were also IgM antibody positive had lower scores than their IgM negative counterparts. The grade of histological severity is more accurately predictable from knowledge of both the HCV RNA and IgM anti HCV status of the patient.

Female↗

The effect of light drinking on HCV liver disease: the jury is still out.

We carried out a study to determine if light drinking (1 unit alcohol/d) adversely affected liver histology in hepatitis C virus (HCV)-associated liver disease. Twenty-eight women who developed chronic hepatitis C (all genotype 1b) as a result of receiving contaminated anti-D immunoglobulin (Ig) had their alcohol intake assessed. Group I (n = 8) took no alcohol, Group II (n = 8) consumed less than one unit monthly and Group III (n = 12) took between two and 18 units (mean = 6.7 units) per week. All 28 subjects had a liver biopsy performed and their histology scored according to the global Knodell score (KI) and the international score for both inflammatory grading (II) and fibrotic staging (FI). The three scores were compared between the three groups and differences tested for significance. The median score for the three groups were Group I: KI = 2, II = 2 and FI = 0; Group II: KI = 4, II = 3.5 and FI = 0.5; Group III: KI = 5.5, II = 4 and FI = 1.5. Initial analysis showed that there was no difference between those who abstained from alcohol and those with a less than monthly consumption; these groups were united and compared with the light drinkers. On Mann-Whitney U test analysis, the P values for the differences between the light drinkers and the combined groups were 0.666 (KI), 0.159 (II) and 0.080 (FI) These results show a trend towards greater histological abnormality in people drinking one unit of alcohol per day, but larger groups will need to be assessed to determine if this is a true or chance finding.

Adult↗

Interferon-associated thyroid dysfunction in anti-D-related chronic hepatitis C.

To assess the frequency and nature of thyroid abnormality in association with interferon (IFN) therapy alone and in combination with ribavirin, 19 patients receiving IFN therapy for hepatitis C virus (HCV)-induced liver disease had thyroid function tests assessed on a monthly basis. Group I (n = 9) patients received 5 million U of IFN s.c. daily for 2 weeks, followed by 3 million U three times per week for 6 months. Group II (n = 10) patients received 3 million U IFN s.c. three times per week together with ribavirin 400 mg twice daily orally for 6 months. Five of 19 patients (26.3%) developed thyroid abnormalities, 3 (33.3%) in group I and 2 (20%) in group II. Three patients developed thyroid function tests consistent with hyperactivity, and 2 of these normalized on cessation of IFN therapy. One patient continued on IFN but remained clinically euthyroid with antithyroid treatment. Two patients developed thyroiditis and required thyroid supplementation. (One of the 2 had pretreatment antimicrosomal thyroid antibodies and a positive family history of thyroid disease.) Of the 3 patients with HCV type 1b, 1 had pretreatment thyroid antibodies, and all 3 had antibodies during IFN therapy. Neither of the 2 patients with genotype 3 had pre-IFN or post-IFN thyroid antibodies. Patients on IFN therapy need regular thyroid function testing. The frequency of abnormal thyroid tests may be dose related. HCV genotype may influence the development of thyroid antibodies.

Antiviral Agents↗

Autoimmune disease is not a feature of hepatitis C infection in Ireland.

To determine the prevalence of autoimmune disease, autoantibody positivity, or both in Irish persons with hepatitis C, we surveyed 98 such patients (55 recipients of anti-D, 25 intravenous drug abusers, and 18 blood transfusion recipients). We studied them clinically and tested for anti-nuclear, anti-smooth muscle, and anti-mitochondrial, liver-kidney microsomal, thyroid microsomal, thyroid globulin, and gastric parietal antibodies; and also for rheumatoid factor. In the anti-D antibody group (all female), two patients reported generalized musculoskeletal symptoms but had no demonstrable physical signs. We did not find cryoglobulins in any patient. We detected thyroid microsomal antibodies in only 6 of 55 (10.9%) patients. (In two of these, thyroid globulin antibodies were also positive). These patients were all clinically euthyroid, but two had borderline low-normal thyroid function tests. Titers for anti-nuclear antibodies were weakly positive in 5 of 55 (9.1%) patients, and gastric parietal antibodies were positive in 5 of 55 (9.1%) patients. In particular, we noted no antibodies to liver-kidney microsome. Rheumatoid factor was detected in eight patients. Forty-seven of 55 patients were genotype 1b, and 8 of 55 were genotype 3. In the intravenous drug abusers (8 women, 17 men), we detected no autoantibodies. Seven of the 25 genotypes were tested; three were genotype 3 and four were genotype 1b. In the transfusion group (10 women, 8 men), we detected no autoantibodies apart from weak anti-nuclear antibody Titers (1:10), which we found three patients. Five of 10 genotypes tested were of genotype 3 and the other five were of genotype 1b. These findings suggest that in Irish patients with hepatitis C, neither genotype nor source (and dose) of inoculum contributes to the development of autoimmune disease. How hepatitis C virus is associated with autoimmune disease in other studies remains unknown. The answer may, at least in part, be found in genetic; HLA typing studies should provide useful information.

Adult↗

Jaundice at onset signifies a good prognosis in anti-D-associated HCV infection.

INTRODUCTION: Acute hepatitis presenting with jaundice occurs in less than a quarter of patients infected with the hepatitis C virus (HCV). These patients may be associated with a more benign clinical course than those who are asymptomatic. OBJECTIVE: To compare and contrast the polymerase chain reaction (PCR) and recombinant immunoblot assay (RIBA) status, serum alanine aminotransferase (ALT) levels and histological scores in age, disease duration and viral load matched HCV anti-D recipients with and without a history of jaundice. METHODS: HCV status was confirmed by detecting HCV-RNA by PCR and antibodies to HCV using enzyme-linked immunosorbent assay (ELISA) and RIBA-3. Serum ALT levels were measured in all patients and a liver biopsy was performed in 26/34 patients. All patients were genotyped. RESULTS: Fourteen out of 17 jaundiced patients were PCR negative and only 4/17 had RIBA scores greater than 9, whereas all non-jaundiced patients were PCR positive and all 17 had RIBA scores greater than 9. Thirteen out of 17 jaundiced patients had normal ALT values, 3/17 mildly elevated (41-100) and 1/17 greater than 100; 6/17 non-jaundiced patients had normal ALT levels, 9/17 mildly elevated (41-100) and 2/17 greater than 100; 7/9 jaundiced patients had mild histological scores, 0/9 moderate and 2/9 severe; 5/17 non-jaundiced patients had mild, 9/17 moderate and 3/17 severe histological scores. All 34 patients were of genotype 1b. CONCLUSION: Patients with jaundice had lower antibody scores, increased PCR negativity, normal serum ALT levels and low/normal histological scores. Jaundice at onset was an indicator of good prognosis.

Alanine Transaminase↗

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Adult↗

Low rate of HCV transmission from women infected with contaminated anti-D immunoglobulin to their family contacts.

PURPOSE: To analyse the spread of HCV infection from women infected with batch number proven contaminated anti-D immunoglobulin to their family contacts. PATIENTS AND METHODS: Index cases. Sixty women who had been infected with hepatitis C after receiving HCV contaminated anti-D Immunoglobulin. All were positive for HCV antibodies by ELISA (Ortho & Murex, Abbott Laboratories) and RIBA3 (Chiron Corporation, Emerville, California) and were viraemic by PCR for HCV-RNA (Roche Diagnostic Systems, Basel, Switzerland). Liver biopsies were performed in 45 patients. All were in stable longterm relationships. CONTACTS: Fifty-five partners and 170 children were tested for HCV antibodies by ELISA (Ortho, Murex). Any positive contact was also tested for antibody by RIBA-3, HCV RNA by PCR, genotype determined and also had a liver biopsy performed. RESULTS: No male partners and only one child tested positive for HCV antibodies indicating low exposure over a combined time period of 862 years for partners and 2465 years for children. CONCLUSIONS: This study suggests a zero female to male sexual transmission rate of HCV and a low vertical transmission rate in anti-D associated HCV infection.

Biopsy, Needle↗