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J Rakela

Publications and source records attributed to J Rakela.

At least 19 recordsLinked to original sources
PubMed1992

Diagnosis of chronic hepatitis C after liver transplantation by the detection of viral sequences with polymerase chain reaction.

Chronic hepatitis frequently occurs after liver transplantation. The role of hepatitis C virus infection in patients after liver transplantation is unknown, although antibodies to HCV are detected in some of these cases. The use of polymerase chain reaction techniques for the detection of hepatitis C virus RNA should improve sensitivity and specificity, particularly in these immunosuppressed patients. Our goal was to further clarify the role of hepatitis C virus infection in chronic hepatitis occurring after liver transplantation. Patients with chronic hepatitis of uncertain origin after transplantation were identified. Serum samples taken at the time of the most recent liver biopsy that showed chronic hepatitis were tested for anti-hepatitis C virus using enzyme-linked immunoassay and supplemented by recombinant immunoblot assay (recombinant immunoblot assay I and recombinant immunoblot assay II). The samples were also tested for the presence of hepatitis C virus RNA using polymerase chain reaction. Of the 25 patients with chronic hepatitis, 15 (60%) had hepatitis C virus RNA present. Only seven (47%) of these 15 patients had anti-hepatitis C virus detected. Hepatitis C virus is a major cause of chronic hepatitis occurring after liver transplantation. The magnitude of hepatitis C virus infection will be underestimated if only currently available assays for anti-hepatitis C virus are used.

Base Sequence↗
PubMed1992

Duration and specificity of antibodies to hepatitis C virus in chronic active hepatitis.

To determine the duration and specificity of antibodies to hepatitis C virus in hepatitis B surface antigen-negative chronic active hepatitis, sera from 19 patients seropositive by enzyme immunoassay were assessed by recombinant immunoblot assay. Only 12 of the 19 patients were reactive by immunoblot assay (63%). Patients nonreactive by immunoblot assay had lower signal-cutoff ratios by enzyme immunoassay (1.3 +/- 0.2 vs. 6.5 +/- 0.1; P less than 0.05), higher serum immunoglobulin G levels (4082 +/- 301 vs. 1760 +/- 143 mg/dL; P less than 0.05), and higher serum gamma globulin levels (3.3 +/- 0.5 vs. 2.04 +/- 0.1 g/dL; P less than 0.05) than reactive patients. Twelve of 14 patients with serial studies remained seropositive after 39 +/- 11 months of follow-up (range, 7-113 months). Only patients nonreactive by immunoblot assay became seronegative by enzyme immunoassay during corticosteroid therapy (2/3 vs. 0/6 patients). It is concluded that seropositivity by enzyme immunoassay may not be documented by immunoblot assay. Patients nonreactive by immunoblot assay have lower signal-cutoff ratios and higher gamma globulin levels than reactive patients, and their seropositivity may be nonspecific. Patients nonreactive by immunoblot assay may lose seropositivity by enzyme immunoassay during corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1992

Frequency of antibody to hepatitis C virus in asymptomatic HBsAg-negative chronic active hepatitis.

To determine the frequency of antibodies to hepatitis C virus in asymptomatic patients with HBsAg-negative chronic active hepatitis, sera from 30 consecutive patients with few or no symptoms of liver disease were tested by an enzyme immunoassay. The reactivity of antibodies detected by enzyme immunoassay against hepatitis C virus encoded antigens was determined by recombinant immunoblot assay. Antibodies were detected in 11 of the 30 patients (37%) and eight of the seropositive sera (73%) were reactive by recombinant immunoblot assay. Nonreactive patients were weakly positive by enzyme immunoassay (sample/cutoff ratio, less than or equal to 1.9) in contrast to reactive patients (sample/cutoff ratio, greater than or equal to 6.3). The prevalence of immunoserologic markers was similar in patients with and without antibodies (78 vs. 87%) but high titers (greater than or equal to 1:160) were more common in seronegative patients (53 vs. 11%). Additionally, seronegative patients had smooth muscle antibodies (83 vs. 25%, p less than 0.05) and concurrent extrahepatic immunologic diseases (37 vs. 9%) more commonly than seropositive counterparts. We conclude that asymptomatic patients with HBsAg-negative chronic active hepatitis frequently have antibodies to hepatitis C virus. These antibodies commonly react to specific viral antigens, especially if the enzyme immunoassay is strongly positive. Seropositive patients infrequently have concurrent immunologic disorders or smooth muscle antibodies. Immunoserologic markers lack diagnostic specificity except in higher titer.

Antibody Specificity↗
PubMed1991

A double-blinded, randomized trial of hydrocortisone in acute hepatic failure. The Acute Hepatic Failure Study Group.

The Acute Hepatic Failure Study Group (AHFSG) has conducted a double-blinded, randomized evaluation of hydrocortisone in patients with acute hepatic failure. From July 1975 through August 1978, a 38-month period, 18 medical centers in the United States and one in Canada participated in this trial. A total of 64 patients were accessed and found eligible to participate in the study; two of them were subsequently eliminated from our analysis. Eighteen patients received placebo; 23 received 400 mg hydrocortisone per day, and 21 patients were administered 800 mg hydrocortisone per day. We did not observe any therapeutic effect of hydrocortisone, and the survival rates for placebo versus 400 mg and versus 800 mg hydrocortisone per day were 22%, 9%, and 24%, respectively. Fulminant hepatitis associated with drug hepatotoxicity or non-A, non-B hepatitis seemed to have a worse prognosis than fulminant B, although these differences were not significant. Serum alpha-fetoprotein had a modest prognostic value of survival and seemed to be limited to fulminant B. The AHFSG recommends, therefore, that corticosteroid use in acute hepatic failure with hepatic encephalopathy be discontinued.

Adult↗
PubMed1991

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated autoimmune chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe autoimmune chronic active hepatitis, we tested sera from 85 cortico-steroid-treated patients by an enzyme immunoassay. Seropositive patients were assessed for specific antibodies to hepatitis C virus-encoded antigens by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only 5 of the 85 patients with autoimmune hepatitis (6%) were seropositive for anti-HCV, and only 2 of these patients were reactive by recombinant immunoblot assay. The frequency of seropositivity in autoimmune hepatitis was not significantly different from that in hepatitis B surface antigen-positive (9%) and cryptogenic (18%) disease, but it was significantly less than that in posttransfusion chronic active hepatitis (6% versus 75%; P less than 0.001). Two patients became seronegative after corticosteroid therapy; both had been nonreactive by recombinant immunoblot assay. Four of the seropositive patients entered remission during corticosteroid therapy, including three whose sera were nonreactive to virus-encoded antigens. We conclude that anti-HCV occurs infrequently in corticosteroid-treated severe autoimmune hepatitis and that antibodies detected by enzyme immunoassay may be nonreactive to hepatitis C virus-encoded antigens. Seropositive patients who are nonreactive by immunoblot assay may still respond to corticosteroid therapy and become seronegative during treatment.

Adult↗
PubMed1990

Clinical and prognostic implications of HLA B8 in corticosteroid-treated severe autoimmune chronic active hepatitis.

To assess the clinical and prognostic implications of human leukocyte antigen B8 in corticosteroid-treated severe autoimmune chronic active hepatitis, 81 consecutive patients were tested for histocompatibility antigens on the A and B loci, treated with corticosteroids, and followed prospectively for 111 +/- 8 mo. The 47 patients with HLA-B8 were younger (38 +/- 2 yr vs. 48 +/- 2 yr; p less than 0.01), had higher serum levels of aspartate aminotransferase (658 +/- 60 U/L vs. 465 +/- 49 U/L; p = 0.02) and bilirubin (7 +/- 1 mg/dl vs. 2.8 +/- 0.4 mg/dl; p = 0.003), and more commonly had histologic features of bridging necrosis, multilobular necrosis, and cirrhosis (85% vs. 56%; p less than 0.01) at presentation than the 34 patients without HLA-B8. Remission (79% vs. 71%), relapse after drug withdrawal (76% vs. 71%), treatment failure (13% vs. 6%), progression to cirrhosis (46% vs. 32%), and death from liver failure (6% vs. 3%) occurred as frequently in patients with and without HLA-B8. Importantly, HLA-B8-negative patients with HLA-A1 relapsed less frequently than HLA-B8-positive patients with and without HLA-A1- and HLA-B8-negative counterparts without HLA-A1. It is concluded that HLA-B8-positive patients are younger and have more severe disease at presentation than HLA-B8-negative patients. The HLA-B8 phenotype does not influence the response to corticosteroid therapy. HLA-B8-negative patients with HLA-A1 relapse less frequently than other phenotypes.

Adult↗
PubMed1990

A 21-year experience with major hemorrhage after percutaneous liver biopsy.

Nine thousand two hundred twelve liver biopsies were performed according to a defined protocol, and data were prospectively recorded to identify risk factors for major bleeding. There were 10 fatal and 22 nonfatal hemorrhages (0.11% and 0.24%, respectively). By comparison with a control group that did not hemorrhage, malignancy, age, sex, and the number of passes were the only predictable risk factors. The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4%; for nonfatal hemorrhage, 0.57%. In patients undergoing liver biopsy for nonmalignant disease, the risks are 0.04% and 0.16%, respectively.

Adolescent↗
PubMed1990

Clinical features and prognostic implications of severe corticosteroid-treated cryptogenic chronic active hepatitis.

To assess the nature and prognosis of severe chronic active hepatitis of unknown cause, we compared 26 patients who had been fully screened for etiologic factors with 112 patients who had autoimmune chronic active hepatitis after similar durations of corticosteroid therapy (17(+)/- 2 versus 23 (+)/- 2 months), and follow-up versus 103 +/- 7 months). Patients with cryptogenic disease could not be distinguished from those with autoimmune disease on the basis of age, sex distribution, duration of illness, immunoglobulin levels, frequency of concurrent immunologic disorders, or histologic findings. Serum gamma-globulin levels were higher (3.4 +/- 0.1 versus 2.5 +/- 0.2 g/dl, P = 0.007) and albumin levels were lower (2.9 +/- 0.1 versus 3.3 +/- 0.1 g/dl, P = 0.003) in patients with autoimmune disease than in those with cryptogenic disease, but individual findings did not differentiate the patients. Remission (69 versus 75%), treatment failure (23 versus 13%), relapse after drug withdrawal (67 versus 68%), progression to cirrhosis (57 versus 36%), and death from hepatic failure (12 versus 11%) occurred as commonly in patients with cryptogenic as in those with autoimmune disease. Patients with different constellations of immunoserologic findings were similar clinically. We conclude that patients with severe chronic active hepatitis who have been fully screened for etiologic factors cannot be distinguished from patients with autoimmune disease of comparable severity. These two groups of patients have a similar prognosis after corticosteroid therapy, and such treatment should be considered in these highly selected patients.

Adult↗
PubMed1990

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated cryptogenic chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe cryptogenic chronic active hepatitis (CAH), we tested sera from 17 corticosteroid-treated patients by an enzyme immunoassay. Specificity of the antibodies to HCV-encoded antigens was assessed by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only three patients (18%) with severe cryptogenic CAH had anti-HCV. Sera from two of these patients were reactive by recombinant immunoblot assay; the other sample produced an indeterminate reaction. The frequency of seropositivity in patients with cryptogenic disease was not statistically different from that in patients with autoimmune CAH (6%), hepatitis B surface antigen-positive CAH (9%), or alcoholic liver disease (0%), but it was significantly less than in those with posttransfusion CAH (18% versus 75%; P less than 0.01). Seropositive patients tended to have lower serum aspartate aminotransferase, gamma-globulin, and bilirubin levels than seronegative counterparts, and they did not have histologic features of confluent necrosis at initial assessment. Two of the three seropositive patients, both of whom had been reactive by recombinant immunoblot assay, entered remission during therapy, and one, with an indeterminate reaction, died of liver failure. We conclude that anti-HCV occurs infrequently in severe corticosteroid-treated cryptogenic CAH. Seropositive patients may have less severe inflammatory activity than seronegative counterparts. Cryptogenic disease may improve during corticosteroid treatment, a result suggesting an underlying immunologic disorder in some patients.

Adult↗
PubMed1990

Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial.

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.

Adult↗
PubMed1990

Treatment of highly symptomatic polycystic liver disease. Preliminary experience with a combined hepatic resection-fenestration procedure.

Polycystic liver disease (PLD) associated with autosomal dominant polycystic kidney disease is usually well tolerated. However there is a small subset of patients who become incapacitated by massive liver enlargement and for whom effective nonsurgical therapy is limited. Recent surgical advances in the treatment of PLD have raised uncertainties regarding proper management of these highly symptomatic patients. We have reviewed our recent experience with a combined hepatic resection-fenestration procedure to assess its efficacy in nine patients. All patients underwent resection of two or more liver segments and extensive fenestration of residual cysts in the remnant liver. Symptomatic relief and reduction in abdominal girth were obtained in eight surviving patients, persisting for an average follow-up period of 17 months. No progression of cystic disease has been observed clinically or by computed tomography and hepatic function was preserved. Three patients had no complications. Five patients had complications including transient right pleural effusion (3) and thrombosis of an arteriovenous fistula (2). One patient who had a previous hepatic cyst fenestration and a cadaveric renal transplantation died after operation of an intracerebral hemorrhage after experiencing coagulopathy, hyperbilirubinemia, and sepsis. Our results suggest (1) some highly symptomatic patients with massive PLD may benefit from combined hepatic resection and fenestration with acceptable risk, and (2) previous liver surgery and immunosuppressive therapy may increase the risk of such surgery. Longer follow-up is needed in a larger number of patients to determine the duration of benefit from the combined resection-fenestration procedure for highly symptomatic PLD.

Adult↗
PubMed1990

The liver in autosomal dominant polycystic kidney disease. Implications for pathogenesis.

A histomorphometric and clinico-pathologic analysis of 26 autopsy cases of autosomal dominant polycystic kidney disease (ADPKD) showed that (1) the density of biliary microhamartomas (BMHs) and the stage of polycystic liver disease were strongly correlated, and (2) both were positively correlated with the stage of renal dysfunction and age at autopsy. Using multiple linear regression analysis, only the stage of renal dysfunction was significantly predictive of the density of BMHs, but both variables were simultaneously predictive for the stage of polycystic liver disease. On serial sections, 41.4% of cysts were connected to BMHs and 81.0% of BMHs to portal tracts. Bile-like material was found in 10.7% of BMHs. Flat or polypoid hyperplasia of the epithelium was observed in 2.7% of cysts. These results support the long-maintained view that hepatic cysts in ADPKD result from cystic dilatation of BMHs. They indicate, however, that the number of BMHs increases during life. These observations are consistent with the hypothesis that hepatic and renal cysts in ADPKD have similar pathogeneses, that BMHs and hepatic cysts result from hyperplasia of the bile duct epithelium, and that as they grow, the hepatic cysts become disconnected from the biliary ducts from which they are derived.

Adult↗
PubMed1989

The nature of unexplained chronic aminotransferase elevations of a mild to moderate degree in asymptomatic patients.

To determine the nature of unexplained chronic serum aspartate aminotransferase elevations of a mild to moderate degree in asymptomatic patients, we performed systematic clinical, biochemical and histologic examinations in 47 individuals who had been screened for virus-, alcohol- or drug-related disease. Serum aspartate aminotransferase levels ranged from 3- to 8-fold normal (mean: 156 +/- 7 units per liter) for at least 6 months (mean: 30 +/- 6 months). Serum alanine aminotransferase levels were also increased but to a lesser degree in most patients. Thirty-four patients (72%) had histologic features of chronic active hepatitis, including 16 with cirrhosis. Ten patients (21%) had steatohepatitis and three (6%) had miscellaneous disorders. Patients with chronic active hepatitis and cirrhosis could not be distinguished from counterparts without cirrhosis by individual clinical or laboratory findings. Antinuclear or smooth muscle antibodies were detected in 18 of the patients with chronic active hepatitis (53%). All patients with steatohepatitis were women, and they had laboratory changes at presentation, including seropositivity for antinuclear antibodies, that overlapped with those of patients with chronic active hepatitis. We conclude that asymptomatic patients with unexplained chronic aspartate aminotransferase elevations of a mild to moderate degree frequently have chronic active hepatitis and that many have cirrhosis. Immunoserologic findings compatible with autoimmune hepatitis are commonly present. Steatohepatitis is the most frequent alternative diagnosis, especially in women, and it is not excluded by the presence of antinuclear antibodies. Differentiation of the disorders is possible only by histologic examination.

Adult↗
PubMed1989

Intraoperative blood loss and patient and graft survival in orthotopic liver transplantation: their relationship to clinical and laboratory data.

We reviewed the records of 83 patients who underwent 100 orthotopic liver transplantations in order to determine the following: (1) the methods to predict blood usage, (2) the consequences of an ABO-incompatible transplant, (3) the benefit of providing cytomegalovirus (CMV)-negative blood products to CMV-negative patients receiving a liver from a CMV-negative donor, (4) the association of donor anti-hepatitis B core antigens and subsequent hepatitis B, and (5) the prognostic consequences of rouleaux observed in pretransplant blood compatibility testing. Patient diagnosis, the presence of ascites, a preoperative prothrombin time greater than 15 seconds, and a multifactorial "risk category" were all predictive of intraoperative blood loss. A history of previous gastrointestinal bleeding or an operation that involved the right upper abdominal quadrant was not predictive of intraoperative blood loss. Although CMV infection is common after liver transplantation, the prophylactic use of CMV antibody-negative blood products in CMV-negative recipients receiving a liver from a CMV-negative donor in our series was not associated with postoperative CMV infection. The transplantation of a liver positive for anti-hepatitis B core antigen was associated with subsequent hepatitis B surface antigen seroconversion in two of four cases. Transplantation of an ABO-incompatible liver and the presence of rouleaux observed in pretransplant blood compatibility testing were both associated with a significantly higher mortality. A careful review of laboratory data and medical records of patients undergoing liver transplantation should enhance the ability to modify the approach to the allocation of limited blood resources and the care and management of these patients.

Adult↗