HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease.

HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in the regulation of the immune system, expressed by HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and B) and II (DR) antigens were studied by serological techniques. Detection of ANCA was carried out in all patients by an indirect immunofluorescence method. The relative frequencies of HLA antigens were compared with a control group made up of 156 blood donors. The control group for the ANCA study was made up of 100 individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in patients with ulcerative colitis. No significant differences were found between patients with Crohn"s disease and controls regarding HLA typing. We detected a significant increase of HLA-DR3 in extensive forms of ulcerative colitis. Detection of ANCA was positive in 46% of the patients with ulcerative colitis and in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the association found between HLA-DR3 and extensive forms of ulcerative colitis provides evidence of genetic heterogeneity. The relationship between ANCA and HLA phenotype (although not significant) supports this concept.

De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population.

Transmission of hepatitis B virus (HBV) infection from donors who are negative for hepatitis B surface antigen (HBsAg-) but positive for antibody to hepatitis B core antigen (anti-HBc+) has been reported. However, previous studies were generally performed in geographic regions with a low prevalence of anti-HBc positivity in the liver donor population. The aims of this study are (1) to assess the risk for de novo hepatitis B in recipients of livers from anti-HBc+ donors in an area of high prevalence of anti-HBc positivity in the donor population, and (2) to analyze the risk factors for acquisition of HBV infection from anti-HBc+ donors. The transplantation experience of a single center between 1995 and 1998 was reviewed. Thirty-three of 268 liver donors (12%) were HBsAg- and anti-HBc+ during the study period. The proportion of anti-HBc+ donors increased with age; it was lowest (3.6%) in donors aged 1 to 20 years and highest (27.1%) in donors aged older than 60 years. Of the 211 HBsAg- recipients with 3 months or more of HBV serological follow-up, 30 received a liver from an anti-HBc+ donor and 181 received a liver from an anti-HBc- donor. Hepatitis B developed in 15 of 30 recipients (50%) of livers from anti-HBc+ donors but in only 3 of 181 recipients (1.7%) of livers from anti-HBc- donors (P < .0001). None of the 4 recipients who were antibody to HBsAg (anti-HBs)+ at the time of transplantation developed HBV infection after receiving a liver from an anti-HBc+ donor compared with 15 of 26 recipients (58%) who were anti-HBs- (P =.10). None of the 5 anti-HBc+ recipients developed hepatitis B compared with 15 of 25 anti-HBc- recipients (60%; P = 0.04). Child-Pugh score was significantly higher in recipients of livers from anti-HBc+ donors who developed HBV infection than in those who did not (9 +/- 2 v 7 +/- 1; P =.03). In our area, testing liver donors for anti-HBc is mandatory, particularly in older donors. With such information available, anti-HBc+ donors can be safely directed to appropriate recipients, mainly those with anti-HBs and/or anti-HBc at the time of transplantation. In the current era of donor shortage, this policy would allow adequate use of such donors.

Progression of cardiomyopathy and neuropathy after liver transplantation in a patient with familial amyloidotic polyneuropathy caused by tyrosine-77 transthyretin variant.

Familial amyloidotic polyneuropathy is an inherited form of amyloidosis associated with a mutant form of a protein called transthyretin. The Methionine-30 variant is the most frequent mutation observed. This disorder is caused by deposition of this protein as amyloid in several organs, such as the heart, kidneys, and peripheral nervous system. The disease is always progressive and fatal, and patients die 7 to 10 years after the onset of symptoms. Liver transplantation is at present the only choice for these patients because it provides improvement of symptoms and/or stops progression of the disease in most patients. We report the case of a patient who showed clear progression of cardiomyopathy and neuropathy after liver transplantation.

High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes.

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine-based HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporine-based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P =.02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P =.001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P =.008 and.18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First-year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.

[Significance of the determination of antineutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis and Crohn's disease]. / Significado de la determinación de anticuerpos frente al citoplasma de los neutrófilos (ANCA) en la colitis ulcerosa y en la enfermedad de Crohn.

We have studied prospectively 126 consecutive patients recruited with a known diagnosis of ulcerative colitis (UC; n = 78) and Crohn's disease (CD; n = 48) for anti-neutrophil cytoplasmatic antibodies (ANCA) by indirect immunofluorescence (IFI). Forty-six percent of UC and 18% of CD patients were found positive. The sensitivity and specificity for UC diagnosis were 0.46 and 0.81, respectively. We evaluated the pattern of IFI exhibited (perinuclear: pANCA and cytoplasmatic: cANCA). cANCA was found in 77% of CD and in only 30% of UC patients (p = 0.01). Sera from all CD patients were positive at a 1:20 dilution (and not at higher dilution) and it occurred in only in 14 UC patients (30%). Positive sera were also tested to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA) but the antigenic nature of ANCA could not be identified in most cases. No differences were found between ANCA positive and ANCA negative patients regarding colonic extension (UC) or colonic involvement (CD), activity and colectomy. We conclude that ANCA may be a helpful diagnostic test in UC patients but it not seems to be important as a marker of activity. ANCA positivity can reflect disease heterogeneity in UC patients, perhaps discriminating those with immunologic disturbances.

Relationship between smoking and colonic involvement in inflammatory bowel disease.

UNLABELLED: The effects of smoking on the onset and clinical course of inflammatory bowel disease (IBD) have been widely debated. Although smoking appears to have a clearly unfavorable effect on the course in Crohn's Disease (CD), the relationship between smoking and localization of the disease is less clear. AIM: To evaluate, in our group of patients, the relationship between smoking and the development of ulcerative colitis (UC) or CD, and between smoking and the localization of CD in the large bowel or in other sites. PATIENTS AND METHODS: The smoking habits of 171 patients at the time of diagnosis were assessed with a questionnaire. Subjects were classified into three subgroups as smokers, nonsmokers and ex-smokers. Current smokers were grouped according to their level of consumption as those who smoked fewer than or more than 10 cigarettes per day. A total of 161 patients were studied (UC n = 69, CD n = 92). Patients with CD were divided into those with colonic disease and those with no colonic involvement. We evaluated the relationship between smoking and the form of IBD, localization (colonic or noncolonic) and the presence of perianal disease (PAD) in CD. The results were analyzed with the chi-squared test. RESULTS: Smoking was more frequent in patients with CD than in those with UC (72.8% vs 31.9%). Among patients with CD, more patients without colonic involvement were smokers (84.6% vs 64.2%). However, among patients with CD involving the colon, smoking was significantly more common (64.2%) than among patients who had UC (31.9%). CONCLUSIONS: Our findings confirm a relationship between smoking and CD. Smoking seems to be associated with some degree of protection of the colonic mucosa, especially in heavy smokers.

[Cholestatic hepatitis caused by amoxycillin-clavulanic acid. Report of a new case]. / Hepatitis colestásica por amoxicilina-clavulánico. Presentación de un nuevo caso.

Toxic hepatitis is an infrequent secondary effect of amoxycillin-clavulanic acid with fewer than 30 well documented cases in the literature. Presentation is usually that of acute cholestasis several weeks after the initiation of treatment with this antibiotic. A new case of hepatic toxicity by amoxycillin-clavulanic acid is reported in a 47-years-old male who had taken this drug for a diarrhea syndrome. A brief review of the literature is made with special emphasis on the anatomopathologic aspects.

[Surgery of benign obstruction of the bile tract. Current opinion status]. / Cirugía de la obstrucción benigna de la vía biliar. Estado actual de opinión.

Treatment of the benign obstruction of the main bile duct remains controversial. A questionnaire, containing the different aspects of the treatment, was mailed in order to learn the general opinion about its management in our country; 140 specialists were surveyed with the following results: 35% gave valid answers. Most of those surveyed (85%) use antibiotic prophylaxis, preferably (79%) pre and postoperatively. Ultrasonography is used in 100% of the cases, and the second most common examination is endoscopic retrograde colangiopan-creatography. Among the intraopreoperative examinations, colangiography is the most used (100%), followed by choledochoscopy. A majority (90.4%) of those surveyed employ the T-tube and 67.5% prefer choledochoduodenostomy if an internal bile drainage must be performed. In obstructive jaundice, only 27.5% recommend preoperative percutaneous drainage. Endoscopic sphinterotomy is the elective technique for suppurative cholangitis and for patients with choledocholitiasis and previous cholecystectomy.

Acquired trichomegaly and hypertrichosis in metastatic adenocarcinoma.

We report the case of a non-HIV patient suffering from a metastatic renal adenocarcinoma who developed trichomegaly 3 months before death. The patient also developed generalized hypertrichosis of the terminal hair, a feature that has been previously described in malnutrition. Other cases of hypertrichosis, including ectopic hormone production, were excluded and the differential diagnosis with paraneoplastic acquired hypertrichosis lanuginosa is discussed. Although trichomegaly is usually considered as a cutaneous marker of AIDS, we suggest that both trichomegaly and hypertrichosis of the terminal hair were secondary to malnutrition.