Interactions between intestinal tapeworms and their hosts: present knowledge and problems

The 1968 classification of chronic hepatitis distinguished cirrhotic and non-cirrhotic stages, and classified the disease according to the histological degree of disease activity into chronic persistent and chronic aggressive (active) varieties. This seemed appropriate at a time when the aetiology of chronic hepatitis was unknown, and presumed to be auto-immune. Immunosuppressive treatment was reserved for more severe variant of the disease, thus validating the usefulness of the classification. Over the past thirty years, several aetiologies were discovered for chronic hepatitis: the hepatitis viruses B, D, C, and G, side-effects of several therapeutic drugs, and autoimmune hepatitis. This progress created a growing need for a new or adapted classification of chronic hepatitis, since different aetiologies require divergent therapeutic approaches. In 1994, proposals for a new classification of chronic hepatitis came from two international organizations: the International Association for the Study of the Liver and the World Congresses of Gastroenterology. The essence of the proposals includes: primary classification according to aetiology, and determination of disease severity (grading) and stage of progression (staging). Several semiquantitative scoring systems for histological grading and staging of liver biopsies from patients with chronic hepatitis are available. Semiquantitative scoring is useful in the evaluation of new treatment regimens, and in comparing pre- and posttreatment biopsies. It is not indicated in the routine reporting of liver biopsies.     

Current diagnosis of chronic nonviral hepatitis

Apart from viruses, hepatotoxins, hereditary metabolic disorders, immunological factors and cholestasis may cause chronic hepatitis both clinically and histologically. As far as the etiology is concerned, a complete history can be very helpful. The clinical examination, however, is rarely diagnostic. Nevertheless, some clinical signs (e.g. ascites, splenomegaly, spider naevi) are suggestive of cirrhosis. The activities of gammaglutamyl transferase and ALT in the serum are augmented in most of the patients with chronic hepatitis independent of its etiology. Electrophoresis reveals disturbance of serum albumin and globulin ratios. "Basic' laboratory tests are supplemented by carefully selected additional investigations (e.g. immunological tests) according to the history and clinical data of the individual patient. Retrograde cholangiography is diagnostic in the majority of patients suffering from primary-sclerosing cholangitis. Liver histology, best obtained during laparoscopy, allows classification (and prognosis) of the underlying liver disease in many patients. Results of iron and copper determination in liver tissue are diagnostic in cases of congenital liver disease (hemochromatosis, M. Wilson).     

Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease

Enzymes of phase I (cytochromes P450) and phase II (UDP [uridine diphosphate]-glucuronosyltransferases) of drug metabolism are targets of autoimmunity in the following chronic liver diseases of different etiology: 1)autoimmune hepatitis (AIH); 2) hepatitis associated with the autoimmune polyendocrine syndrome type 1 (APS-1); 3) virus-induced autoimmunity; and 4) drug-induced hepatitis. AIH is diagnosed by the following: the absence of infection with hepatitis viruses; the presence of a threshold of relevant factors, including circulating autoantibodies, hypergammaglobulinemia, female sex (female/male ratio 4:1), human leukocyte antigen (HLA) B8, DR3, or DR4; and benefit from immunosuppression. Patients with autoimmune hepatitis type 2 (AIH-2) are characterized by antibodies directed against liver and kidney microsomes, by an early onset of autoimmune hepatitis, which is a more aggressive course of the disease, and by a higher prevalence of autoimmunity directed against other organs. The major target of autoimmunity in patients with AIH-2 is cytochrome P450 2D6. Epitope mapping experiments revealed four short linear epitopes on cytochrome P450 2D6, recognized by liver/kidney microsomal autoantibodies type 1 (LKM-1) in patients with AIH-2. In addition, about 10% of the patient sera contain autoantibodies that detect a conformational epitope on UDP-glucuronosyltransferases (UGTs) of family 1. Presently, LKM-1 autoantibodies are used as diagnostic markers for AIH-2. It is unclear whether these autoantibodies have a pathogenetic role. Hepatitis is found in some patients with APS-1. Presumably this also is an autoimmune liver disease. APS-1 patients with hepatitis may develop autoantibodies directed against microsomal P450 enzymes of the liver; however, these autoantibodies do not recognize cytochrome P450 2D6, but they do recognize cytochrome P450 1A2. Autoimmunity in patients with APS-1 usually is directed against several organs simultaneously, and several organ specific autoantibodies may exist. Interestingly, APS-1 patients may produce various anti-cytochrome P450 antibodies. In addition to the hepatic anti-cytochrome P450, 1A2 autoantibodies are directed against steroidogenic cytochromes P450, namely P450 c21, P450 scc, and P450 c17. These autoantibodies correlate with adrenal and ovarian failure and often these steroidal cell autoantibodies precede the manifestation of adrenal or ovarian dysfunction. Whether anti-P450 1A2 autoantibodies have a similar predictive value is not yet known. LKM autoantibodies are further found in association with chronic hepatitis C and D. In chronic hepatitis C, the major target of LKM autoantibodies is cytochrome P450 2D6. Predominantly, conformational epitopes are recognized by LKM-1 sera of patients with chronic hepatitis C. In 13% of patients with chronic hepatitis D, LKM-3 autoantibody is detectable. The target proteins are UGTs of family 1 and in a minority of sera UGTs of family 2. The epitopes are conformational. All hepatic diseases discussed earlier have in common that autoimmunity, which is directed against enzymes of drug metabolizing multigene families. Each disease is characterized by a specific pattern of autoantibodies, with apparently little overlap. For example, LKM-1 autoantibodies, which are directed against P450 2D6, seem to overlap between AIH and chronic hepatitis C. However, a close examination of these autoantibodies shows differences between LKM-1 autoantibodies from patients with chronic hepatitis C and with AIH. In AIH, LKM autoantibodies are more homogenous, titers are higher, and major autoepitopes on cytochrome P450 2D6 are small and linear. LKM autoantibodies in viral hepatitis C are more heterogeneous and there are multiple epitopes, many of which are conformational. These differences indicate the different mechanisms that are involved in the generation of autoimmunity. (ABSTRACT TRUNCATED)     

Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis

BACKGROUND: Antibodies to soluble liver antigen, P450IID6, and the E2 subunits of mitochondrial dehydrogenase complexes occur in autoimmune liver diseases, but their specificities and implications are uncertain. The aims of the present study were to assess the importance of these autoantibodies in different types of chronic hepatitis. METHODS: Sera from 62 patients with autoimmune hepatitis, 37 patients with cryptogenic hepatitis, and 19 patients with chronic hepatitis C were assessed under code by enzyme immunoassay. RESULTS: Antibodies to soluble liver antigen were found in 7 patients with autoimmune hepatitis (11%) and 5 patients with cryptogenic disease (14%). Patients with antibodies to soluble liver antigen were indistinguishable from seronegative counterparts with autoimmune hepatitis. Seropositive patients with cryptogenic hepatitis had autoimmune features, and they responded to corticosteroid therapy. Five patients (8%) with autoimmune hepatitis were seropositive for antibodies to mitochondrial complexes. Three lacked antimitochondrial antibodies. None of the patients had antibodies to P450IID6, and patients with chronic hepatitis C were seronegative for all markers. CONCLUSIONS: Antibodies to soluble liver antigen do not define a distinct subgroup of patients with autoimmune hepatitis. They may be found in some patients with corticosteroid-responsive cryptogenic hepatitis. Antibodies to E2 subunits and P450IID6 are uncommon in adults with chronic hepatitis.     

Detection and identification of microcystins in the drinking water of Haimen City, China

The main method of classification of chronic viral hepatitis is now by cause, and the old histology-based classification is no longer considered appropriate. However, liver biopsy remains an important part of patient assessment and, in the context of clinical trials, biopsy findings are often scored in a semiquantitative manner. The concepts of grading and staging, borrowed from tumour pathology, have been introduced, representing the severity of the necroinflammatory lesion and the extent of its structural consequences respectively. The pathology of the individual forms of viral hepatitis A to G shows more similarities than differences. However, some pathological features are commonly associated with specific viruses. The combination of portal lymphoid follicles, bile duct damage, lobular activity and steatosis give chronic hepatitis C a characteristic histological profile. Very similar appearances have been noted in the limited number of biopsies so far reported from patients with known combined hepatitis C and G virus infection.     

Autoimmune hepatitis--a rare cause of elevated transaminases

Autoimmune hepatitis is a rare chronic hepatitis of unknown etiology. Immunological changes are conspicuous, with tissue antibodies found in a high proportion of patients. There is a female preponderance of 2-3:1 and the disease often affects young people. The presenting symptoms are vague, fatigue being the most important general symptom. The diagnosis is often made at a late stage of the disease when symptoms of liver decompensation and cirrhosis are obvious. We present two cases of AIH in young women diagnosed at a late stage with advanced cirrhosis, for whom symptoms of liver disease had been intermittently present for 12 and 9 months, but wrongly attributed to presumed acute viral hepatitis acquired on holiday in the Mediterranean. In order not to miss the diagnosis, it is important to confirm suspected viral hepatitis serologically, to look for liver disease stigmata in patients with abnormal liver enzymes, and to be especially aware of the possibility of AIH in young women with concommittant or family history of other autoimmune diseases.     

Hepatitis B virus with X gene mutation is associated with the majority of serologically "silent" non-b, non-c chronic hepatitis

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.     

New hepatitis viruses: are there enough letters in the alphabet?

Testing is now available for five recognised hepatitis viruses (A, B, C, D and E), and molecular technology is uncovering further hepatotropic viruses. An enteric agent isolated from human stool samples and transmitted experimentally to primates is a candidate hepatitis F virus. A provisionally designated blood-borne hepatitis G virus is associated with acute and chronic non-ABCDE hepatitis and has a worldwide distribution. A group of flavi-like viruses, the GB group, also blood borne, has also been reported. The role of two of these viruses, GBV-A and GBV-B, in human viral hepatitis has not been determined, but a third agent, GBV-C, is associated with acute and chronic hepatitis and appears to be a West African variant of hepatitis G. Our current knowledge suggests that the hepatitis alphabet may need to be extended even after inclusion of some of these new viruses.     

Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis

Celiac disease has been associated with autoimmune disorders, but its frequency in autoimmune hepatitis is unknown. Sera from 157 patients with type 1 autoimmune hepatitis, 24 patients with type 2 autoimmune hepatitis, 62 patients with primary biliary cirrhosis, 30 patients with chronic hepatitis B, and 80 patients with chronic hepatitis C were tested for immunoglobulin A anti-endomysial antibodies by indirect immunofluorescence and immunoglobulin A and G antibodies to gliadin by enzyme immunoassay. Duodenal biopsy evaluation was recommended in patients seropositive for immunoglobulin A anti-endomysial antibodies. Immunoglobulin A anti-endomysial antibodies were present in eight of the 181 patients with autoimmune hepatitis (4%), including six with type 1 disease (4%) and two with type 2 disease (8%). Immunoglobulin A antibodies to gliadin were found in six of these eight patients, but they were also present in two others, including one patient with chronic hepatitis C. Five of the eight patients with immunoglobulin A antiendomysial antibodies, including three patients with no gastrointestinal symptoms, had duodenal biopsies and subtotal villous atrophy was present in all of them. No patient with primary biliary cirrhosis or chronic viral hepatitis had antiendomysial antibodies. The presence of celiac disease in autoimmune hepatitis is high (at least one in 36 patients) and it is predominantly asymptomatic. Screening with anti-endomysial and anti-gliadin antibodies should be performed and results confirmed with intestinal biopsy.     

Frequency and significance of phenotypes for alpha1-antitrypsin deficiency in type 1 autoimmune hepatitis

To evaluate the frequency and significance of alpha1-antitrypsin deficiency in type 1 autoimmune hepatitis, 181 Caucasian patients were assessed for variant phenotypes. Three hundred three Caucasian patients with various other chronic liver diseases were similarly evaluated. Twenty-one of the 181 patients (12%) had heterozygous deficiencies, including the MS (6%) and MZ (6%) phenotypes. These patients were indistinguishable from those with normal phenotypes. Immediate outcomes after corticosteroid therapy were also similar in both groups. Variant phenotypes were present in 34 of the 303 patients with other chronic liver diseases (11%). Patients with nonalcoholic steatohepatitis had a significantly greater frequency of deficiency phenotypes than patients with chronic hepatitis C (20% vs 7%, P = 0.03). In conclusion, deficiency phenotypes are common in type 1 autoimmune hepatitis and they have no clinical or prognostic importance. In certain liver diseases, such as nonalcoholic steatohepatitis, variant phenotypes may be comorbid factors.     

Comparison of Ottawa ankle rules and current local guidelines for use of radiography in acute ankle injuries

INTRODUCTION: We report the occurrence of non-Hodgkin's lymphoma during the course of chronic hepatitis C treated with alpha-interferon. EXEGESIS: Specific viruses such as Epstein-Barr virus and human T-cell leukemia viruses I and II may be at the origin of various lymphomas in human. The presence of B cell lymphoma in the course of chronic hepatitis C has already been described and could be related to the lymphoid tropism of hepatitis C virus. CONCLUSION: This new report of an association between chronic hepatitis C and B cell lymphoma should lead physicians to search for signs of lymphoma in patients with chronic hepatitis C.     

Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent

To evaluate the histological findings in patients with chronic hepatitis C and autoimmune features, liver tissue specimens from 60 patients were graded under code for individual features and composite patterns that denoted autoimmune, viral, combined autoimmune and viral, and nondiscriminative changes. Portal, interface, and acinar hepatitis in any combination with plasma cell infiltration connoted an autoimmune pattern that was associated with higher serum levels of gamma-globulin (2.4 +/- 0.2 g/dL vs. 1.7 +/- 0.1 g/dL; P = .0003) and immunoglobulin G (2,211 +/- 227 mg/dL vs. 1,508 +/- 83 mg/dL; P = .001) than patients with other patterns. Patients with the autoimmune pattern also had a greater frequency of cirrhosis (43% vs. 8%; P = .003), higher mean Knodell score (13.2 +/- 0.9 vs. 6.8 +/- 0.9; P < .0001), and a greater occurrence of high-titer smooth muscle antibodies (SMA) (13% vs. 0%; P = .05) than patients with other histological findings. HLA DR3 also occurred more frequently in these individuals than in other patients (48% vs. 15%; P = .01) and normal subjects (43% vs. 16%; P = .01). Patients with nondiscriminative patterns and interface hepatitis had clinical findings similar to those with autoimmune patterns, except for a lower mean serum level of gamma-globulin. We conclude that the composite histological pattern that resembles autoimmune hepatitis is associated with greater immunoreactivity, inflammatory activity, and disease severity than other patterns. Interface hepatitis may be the most important histological finding associated with these clinical manifestations.     

Structure of CheA, a signal-transducing histidine kinase

BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.     

Deduction: moving from the general to the specific

During a 29 month period, 46 patients with chronic hepatitis C virus (HCV) received recombinant human interferon alpha-2a for 6 months and were followed for another 6 months. The dose of interferon was three million units thrice weekly and was increased to six million units if amino transferase levels failed to return to normal after 2 months of therapy. At the end of the treatment 19 patients had a complete response, 6 had a near complete response, 2 patients had breakthrough during treatment, and the remaining 19 did not respond at all. Six months after treatment only 10 of the 19 responders remained in remission. Post-transfusion disease was associated with a significantly higher remission rate than sporadic disease (9/22 vs. 1/24, P < 0.001), as was also found in non-cirrhotic compared to cirrhotic patients (9/27 vs. 1/19, P < 0.001). Age, sex, duration of disease, serum aminotransferase, albumin, bilirubin, alkaline phosphatase, or Child's classification did not correlate with treatment response. Severe side effects necessitating cessation of treatment occurred in six patients, four of whom had major autoimmune phenomena. We conclude that careful selection of HCV patients with favorable response characteristics (post-transfusion etiology and non-cirrhotic liver) and without autoimmune manifestations can improve the remission rate and decrease the complication rate during interferon treatment.     

A prospective evaluation of dermatological side-effects during alpha-interferon therapy for chronic viral hepatitis

OBJECTIVE: Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports. DESIGN: A prospective case-control study. SETTING: A tertiary referral centre. PARTICIPANTS: One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months). INTERVENTIONS: Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more. MAIN OUTCOME MEASURES: To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis. RESULTS: Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions. CONCLUSIONS: This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased.     

Hepatitis G virus infection in hemodialysis patients

The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.     

Growth pattern and age at menarche of obese girls in a transitional society

The diagnosis of cirrhosis relies on the histological analysis of a liver sample provided by biopsy made by transparietal or transjugular route according to the haemostasis of the patient. The histological study allows also to characterize the causative process and the severity of the disease. In the absence of histological proof a high probability of cirrhosis could be assumed when a firm liver with a narrow inferior edge is associated or not with signs of hepatic failure or portal hypertension. The most common causes of cirrhosis in France are alcohol abuse, C and B viruses, genetic haemochromatosis, chronic active autoimmune hepatitis, primary biliary cirrhosis. The prevalence of viral causes is increasing.     

Effect of training on general practitioners'' use of a brief intervention for excessive drinkers

During recent years the outcome of acute hepatitis A in chronic liver disease has been discussed controversially. Data from large hepatitis A epidemics and surveillance data from the United States suggest a significantly higher risk of fatal outcome in patients with chronic hepatitis B. Patients with chronic active hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may exhibit a benign course of the disease. Patients with chronic hepatitis C also seem to have a significantly higher risk of fulminant hepatic failure when superinfected with hepatitis A. The recently reported unsuspected coincidence of autoimmune markers with a fulminant course of hepatitis A in those patients needs to be confirmed. Vaccination against hepatitis A in patients with chronic liver disease has been shown to be safe and effective.     

The effect of interleukin-1alpha on outflow facility in rat eyes

BACKGROUND: There are few reports in Mexico on the prevalence of infection by virus D. OBJECTIVE: The aim of the present study was to study the hepatitis D virus infection prevalence in patients entering to the University Hospital. METHODS: Seventy three HBsAg positive patients sera were studied. There were 38 patients with acute hepatitis, 28 patients with chronic liver disease and 7 were asymptomatic HBsAg carriers. Serological markers for hepatitis viruses B, D and C were detected by means of ELISA test (Abbott). RESULTS: Anti-HDV was detected in 3 cases (4%). The first two cases were men with acute hepatitis B. Both had a coinfection by viruses B and D, however IgM anticore could not be demonstrated in the first case, this patient developed hepatic cirrhosis within 13 months, in addition he had a concurrent infection by hepatitis C virus with a positive second generation ELISA antibody. The second case recovered from the acute hepatitis. The third case was a female nurse with acute hepatitis and a coinfection by viruses B and D who recovered from the acute attack. Antibody to hepatitis C was present in 3 out of 22 patients with chronic liver disease (13.6%), one of them having an hepatocellular carcinoma. CONCLUSIONS: Our results coincide with the previously reported low incidence of hepatitis D and represent the first report in Mexico of concurrent infections by viruses B-C and B-D-C.