Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification.

BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient's first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

Dermatitis herpetiformis: a comparative assessment of skin and bowel abnormality.

We reviewed 18 patients with a clinical diagnosis of dermatitis herpetiformis who were being treated with dapsone and were on an unrestricted diet. Diagnosis was confirmed by finding IgA deposits in the dermal papillae of unaffected skin. Dapsone was discontinued and biopsy of affected skin was carried out when the typical rash reappeared. The biopsy findings were graded according to the severity of the histological changes. Small bowel tissue from each patient was examined and graded by stereo- and routine microscopy. Thirteen specimens (72%) were stereomicroscopically abnormal; all 18 showed villous atrophy, either partial or subtotal; and in 13 (72%) the interepithelial lymphocyte count was increased. No correlation was found between the histological severity of the skin and the small bowel lesions. Seemingly the severity of the skin rash in dermatitis herpetiformis is no guide to the degree of small bowel abnormality.

Coeliac disease and epilepsy.

Whether there is an association between coeliac disease and epilepsy is uncertain. Recently, a syndrome of coeliac disease, occipital lobe epilepsy and cerebral calcification has been described, mostly in Italy. We measured the prevalence of coeliac disease in patients attending a seizure clinic, and investigated whether cerebral calcification occurred in patients with both coeliac disease and epilepsy. Screening for coeliac disease was by IgA endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. Of 177 patients screened, four patients were positive. All had small-bowel histology typical of coeliac disease. The overall frequency of coeliac disease in this mixed patient sample was 1 in 44. In a control group of 488 pregnant patients, two serum samples were positive (1 in 244). Sixteen patients with both coeliac disease and epilepsy, who had previously attended this hospital, were identified. No patient had cerebral calcification on CT scanning. Coeliac disease appears to occur with increased frequency in patients with epilepsy, and a high index of suspicion should be maintained. Cerebral calcification is not a feature of our patients with epilepsy and coeliac disease, and may be an ethnically-or geographically-restricted finding.

Pregnancy and pregnancy outcome in hepatitis C type 1b.

A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

Neuropathy due to podophyllin intoxication.

A 22-year-old man developed a severe sensorimotor neuropathy following ingestion of podophyllin, which had been prescribed for genital condylomata. The initial toxic symptoms were vomiting and diarrhoea, followed by peripheral neuropathy. The neuropathy was still present 18 months later. Nerve conduction studies and sural nerve biopsy confirmed the presence of axonal degeneration.

Perspective in liver disease: An Irish experience.

CONCLUSIONS: Graves travelled extensively and on one trip to Italy in 1819 he was joined by a man he describes as of rough exterior and being more "like a ship's mate" (Widdess, 1963). This man sketched extensively and was in fact the famous English painter - J. M. W. Turner. Graves, who was also sketching, was under no illusion as to who was the master and remarked later to Stokes - "When we compared drawings, the effect was strange. Not a single stroke in Turner's drawing was like nature … and yet my work was worthless in comparison to his. The whole glory of the scene was there". Graves acknowledged Turner's mastery in the field of sketching. No one can deny that this extra-ordinary man, with his clinical observations, deserves his eminent place in Irish medicine. Indeed continued studies of his writings can still prove beneficial to the present day scholar.

Down syndrome and autoimmune chronic active hepatitis: satisfactory outcome with therapy.

A case of autoimmune chronic active hepatitis (C.A.H.) in a 12-year old Down Syndrome child is described. This represents the second only documented case of autoimmune C.A.H. occurring in Down Syndrome; the first well-described case died from the disease. The patient described below had a satisfactory response to steroid therapy with restoration of normal liver histological appearances and function despite severe disease at presentation. Chronic hepatitis in Down Syndrome, although more usually of hepatitis B viral aetiology, may also be autoimmune in nature and resolve satisfactorily with appropriate therapy.

Arterial portography in the management of portal hypertension.

ARTERIAL portography is the study of the spleno-portal venous system by visceral arteriography. Four cases studied by this method are described to illustrate its value. In the management of portal hypertension, detailed knowledge of the cause of the hypertension and the availability of any veins that can be used for shunting purposes is essential; after a decompressive shunt has been performed, its exact status must be known, especially if the patient has gastrointestinal bleeding, or shows evidence of failing hepatic function. Arterial portography should give this information. It provides not only a practical alternative to splenoportography, but a more physiologic means of studying the portal circulation.

Adult infectious diseases: management in a general hospital.

Conflicting views exist as to where patients with infectious diseases (IDs) are best managed. In an effort to define the role of an IDs Unit in this country, we undertook a four-year survey of IDs cases referred to our isolation facility which is part of the Gastroenterology department. Ninety-three per cent of 250 cases referred had either diarrhoea (48%) or jaundice (45%). Two thirds of the total had an infective, and one third a non-infective basis for their illness. Since diarrhoea and jaundice dominated the clinical presentations of these cases, having the IDs facility within the Gastroenterology department made for speedy diagnosis and management of both infectious and non-infectious cases. Where referral and/or transfer to other units was necessary, it still proved helpful to locate the IDs facility within a regional multidisciplinary hospital, particularly in view of the wide range of medical and surgical conditions referred as putative IDs.

Gallstones and laparoscopic cholecystectomy in hepatitis C patients.

Our aims were to determine the incidence of gallstones in a cohort of patients infected with hepatitis C for 20 years, and to analyse the outcome of all patients infected with hepatitis C undergoing laparoscopic cholecystectomy. A hepatitis C screening programme in place in Ireland since 1994 identified 965 patients with hepatitis C antibodies out of 62,667 patients screened. The hepatology unit of Cork University Hospital has 318 patients with hepatitis C. Of patients identified by screening, 201 were post partum women infected via contaminated Anti-D immunoglobulin administered in 1977. Thirty-five (17.4%) of two hundred and one patients with hepatitis C since 1977 had developed gallstones after twenty years. A total of 34 patients with hepatitis C underwent laparoscopic cholecystectomy. One patient required conversion to open cholecystectomy. There were no complications and no mortality. There was a low rate of cirrhosis (11%) on examining liver histology. The incidence of gallstones in a cohort of patients infected with hepatitis C for twenty years approximates to that of the general population. The low rate of cirrhosis in this group may be related to a low consumption of alcohol. Laparoscopic cholecystectomy is a safe procedure in patients with mild chronic liver disease caused by hepatitis C.