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Biomedical subjects

J Rakela

Publications and source records attributed to J Rakela.

At least 127 records · Page 7Linked to original sources
PubMed1994

Lack of evidence for hepatitis B virus (HBV) infection in fulminant non-A, non-B hepatitis.

We studied eight patients who had orthotopic liver transplantation for fulminant hepatic failure in the course of acute non-A, non-B hepatitis. HBV DNA was searched for extensively in the liver tissue by PCR using several sets of primers in conventional and heminested reactions. All patients were negative for HBV DNA in liver tissue by all assays employed; furthermore, they were negative for HEV RNA, HCV RNA, and HBV DNA in serum. Although the causative role of HEV and HCV in fulminant non-A, non-B hepatitis cannot be excluded, our data do not support a causative association between this syndrome and HBV infection.

Base Sequence↗
PubMed1994

Nucleotide sequence analysis of the precore region in patients with spontaneous reactivation of chronic hepatitis B.

The role of HBV precore mutations in the spontaneous reactivation of chronic hepatitis B (CHB) is currently unknown. We studied 10 patients with CHB; five were HBeAg+ (group I) and five were anti-HBe+ (group II). All 10 had spontaneous reactivation of CHB as defined by the appearance of clinical symptoms along with an increase of serum ALT activity at least 5X above baseline values, in the absence of any other known causes of liver disease or CHB reactivation. The precore (87 nt) and proximal core (81 nt) regions were sequenced after PCR amplification. From each patient three serum samples studied: one 3-12 months before, one during, and one six months after reactivation. Prior to reactivation, none of the group I patients harbored an HBV strain having a mutation that prevented HBeAg synthesis; however, 2/5 developed such a mutation during reactivation (G to A transition at nt 1896). Among the group II patients, three harbored an HBeAg defective mutant both before and during reactivation; after six months, two of these three patients were HBV DNA negative in serum by PCR. Several other sequence polymorphisms, some of which changed the predicted amino acid sequence, were either present initially or developed during reactivation. In conclusion, in this small group of CHB patients who were HBeAg+ spontaneous reactivation was accompanied in some cases by a shift to an HBeAg defective mutant, while in patients who were anti-HBe+, such mutations were frequently present prior to reactivation. In patients already harboring precore defective mutants, spontaneous reactivation may precede an attenuation of viral replication.

Adult↗
PubMed1994

Precore and contiguous regions of hepatitis B virus in liver transplantation for end-stage hepatitis B.

BACKGROUND/AIMS: Recurrent hepatitis B virus (HBV) infection is the leading cause of mortality and morbidity after orthotopic liver transplantation (OLT) for HBV-related liver disease, but the extent of viral genetic variation in this setting remains unknown. METHODS: Eight patients who underwent OLT for HBV-related liver disease were studied; 7 had cirrhosis and 1 had fulminant hepatitis. Four patients received long-term hepatitis B immunoglobulin prophylaxis. A 240-base pair fragment (1742-1981) comprising the precore region of HBV was amplified by polymerase chain reaction from sera drawn before OLT and 6, 12, and 24 months after OLT and analyzed. RESULTS: All sera were positive by polymerase chain reaction. Nucleotide sequence variations were congruent within most patients before and after OLT; however, in one patient, substantial sequence variation was observed, suggesting infection with a new HBV strain. No sequence variation associated with a particular outcome could be identified. Two patients harbored HBV variants with a deletion or insertion upstream of the precore messenger RNA initiation site. CONCLUSIONS: Reinfection after OLT can occasionally be caused by HBV strains different from the one present before OLT. Changes within the sequenced region are not predictive of the outcome of reinfection.

Adult↗
PubMed1994

Orthotopic liver transplantation for preoperative early-stage hepatocellular carcinoma.

OBJECTIVE: To report our experience with orthotopic liver transplantation (OLT) for highly selected patients with early-stage hepatocellular carcinoma (HCC). DESIGN: We retrospectively analyzed the demographic, clinical, pathologic, and survival data on 21 patients with HCC who underwent OLT at the Mayo Clinic between 1985 and 1993. MATERIAL AND METHODS: The 21 patients were categorized into three groups: (1) those with incidental HCC (no evidence of HCC preoperatively), (2) those with a unicentric hepatic lesion without vascular invasion, and (3) those with an increased serum alpha-fetoprotein (AFP) concentration but no detectable mass lesion in the liver. RESULTS: For the seven patients with incidental HCC, the 2-year disease-free survival was 68.5%. For the eight patients with a mass lesion, the 2-year disease-free survival was only 50%. Operative staging revealed more advanced stage disease than had been found on preoperative assessment in five of these eight patients. For the six patients with an increased serum AFP value but no mass lesion, the 2-year disease-free survival was 80%. Tumor recurrence was the major cause of all deaths in this series. CONCLUSION: Disease-free survival for patients with radiographic early-stage HCC was suboptimal because of understaging of the disease preoperatively. In contrast, our initial experience with OLT for patients with an increased serum AFP value in the absence of a mass lesion in the liver was favorable.

Adult↗
PubMed1994

Naturally occurring hepatitis B virus mutants with deletions in the core promoter region.

A novel class of hepatitis B virus mutants in patients with chronic hepatitis B is described. The predicted effect of the mutations is to disrupt the X open reading frame. The location of the genetic alterations within the putative precore promoter also suggests that they may ameliorate precore transcription, which would provide an alternate mechanism for HBeAg(-) escape variation. Definitive conclusions regarding the effects of these mutations must await additional in vitro and in vivo studies.

Adult↗
PubMed1994

The liver biopsy diagnosis of Wilson's disease. Methods in pathology.

The authors present a simple liver biopsy protocol that is a reliable and cost-effective method of diagnosing hepatic Wilson's disease. Biopsy specimens are obtained in routine fashion, without the need for copper-free solutions or instruments. The samples are then embedded in paraffin, stained for copper and copper-associated protein, and studied by light microscopy. Subsequently, a sample of hepatic parenchyma is excised from the paraffin block for chemical quantitation of tissue copper. This combination of methods generally yields reliable results and allows confirmation of the diagnosis in cases of Wilson's disease in which special stains for copper are negative. In most instances, electron-microscopic studies are not necessary.

Adult↗
PubMed1994

Non-A, non-B fulminant hepatitis is also non-E and non-C.

OBJECTIVES: to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis. METHODS: we utilized the polymerase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients. RESULTS: none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera. Three patients, all with features of autoimmune hepatitis, had raised IgG-HEV antibody titers. Due to the possibility of serologically undetectable hepatitis B virus (HBV) infection in fulminant hepatitis patients, we performed polymerase chain reaction amplification of HBV genomic DNA in acute phase sera of the presumed viral NANB FHF patients and subsequently found no evidence of HBV DNA. CONCLUSIONS: we did not find evidence implicating HCV or HEV in presumed viral NANB FHF or as agents contributing to or causing the liver failure in nonviral NANB FHF patients with autoimmune hepatitis, drug-induced hepatotoxicity, or halothane hepatotoxicity.

Adolescent↗
PubMed1993

Randomized controlled trial of recombinant alpha-2a-interferon for chronic hepatitis C. Comparison of alanine aminotransferase normalization versus loss of HCV RNA and anti-HCV IgM.

We enrolled 32 patients with chronic hepatitis C into a randomized, controlled trial to evaluate the efficacy of recombinant alpha-2a-interferon treatment. Sixteen patients were randomized to receive 1.5 million units of recombinant alpha-2a-interferon subcutaneously, thrice weekly, for six months while the remaining 16 patients were randomized to a control group that received no treatment. The mean serum alanine aminotransferase (ALT) level during the six-month study period, expressed as a percentage of the prestudy baseline value, was 82% for the control group compared to 56% for the treatment group (P = 0.014). One fourth of the treatment group normalized their serum ALT level compared to only 6% of the controls (P = 0.05). During posttherapy follow-up, 86% of responders clinically relapsed. Loss of anti-HCV IgM and HCV RNA occurred exclusively in interferon-treated responders. Anti-interferon antibodies developed in 32% of all treated patients. Forty percent of nonresponders developed anti-interferon antibodies compared to only 14% of responders (P = NS). We conclude that recombinant alpha-2a-interferon is clinically effective in patients with chronic hepatitis C. However, most responders in this trial of low-dose interferon relapsed upon cessation of treatment.

Adult↗
PubMed1993

Nucleotide sequence analysis of the precore region in patients with fulminant hepatitis B in the United States.

BACKGROUND: A precore defective hepatitis B virus (HBV) mutant unable to produce hepatitis B e antigen (HBeAg) has been associated with fulminant hepatitis B. We have studied the etiologic contribution of precore mutants among North American patients with this disorder. METHODS: We studied 39 patients with fulminant hepatitis B. The precore and proximal core regions of HBV from 37 of 39 patients were sequenced. RESULTS: Four patients (10.8%) harbored nonsense mutants likely to produce an HBeAg negative HBV infection; two such mutants had a G to A substitution at position 1896, one lost the precore initiation codon, and one harbored a stop codon immediately downstream of the precore initiation codon. Recovered sequences from seven additional patients displayed silent or missense mutations in these regions. All delta coinfected patients harbored known wild type strains of HBV. A significantly poorer survival was associated with antibody to HBe positivity and presence of nucleotide substitutions in the precore/core region. CONCLUSIONS: The prevalence of precore mutations in 37 patients from the United States was lower than reported elsewhere; only two patients were found to have the G to A transition mutation in the precore region at position 1896. We conclude that HBeAg negative HBV mutants do not play a predominant etiologic role among North American patients with fulminant hepatitis B.

Adenine↗
PubMed1993

Absence of hepatitis B virus DNA detected by polymerase chain reaction in blood donors who are hepatitis B surface antigen negative and antibody to hepatitis B core antigen positive from a United States population with a low prevalence of hepatitis B serologic markers.

A recent study in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive blood donors from a population with a high prevalence of hepatitis B serologic markers showed the presence of hepatitis B virus DNA (HBV DNA) as detected by polymerase chain reaction (PCR) in 4 percent of these donors. A sensitive, nested PCR assay was used to assess the prevalence of HBV DNA in a population of HBsAg-negative, anti-HBc-positive blood donors from a United States population with a low prevalence of hepatitis B serologic markers. The lower limit for detection by the PCR assay was 10(-5) pg per mL of HBV DNA. There was a review of 26,492 consecutive blood donations in a 12-month period. During this time, only 1 unit (0.004%) was HBsAg positive. An additional 158 units (0.6%) were repeatably reactive for anti-HBc. These 158 HBsAg-negative, anti-HBc-positive units were given by 119 donors of blood for allogeneic and autologous use. HBV DNA was not detected by PCR in blood from 83 allogeneic blood donors (93 samples) or 36 autologous blood donors (65 samples). Anti-HBc testing is an inefficient means of screening for potential hepatitis B infectivity and is associated with low test specificity in populations with a low prevalence of hepatitis B serologic markers.

Adolescent↗
PubMed1993

Prevalence of peritonitis and the ascitic fluid protein concentration among chronic liver disease patients.

The prevalence of spontaneous bacterial peritonitis (SBP) or its variants, bacterascites (BA), and culture-negative neutrocytic ascites (CNNA), may vary depending on the underlying liver disease and protein content of ascites. In this study, we compared the frequency of peritonitis (SBP, BA, CNNA) upon admission in alcoholic (ALD), cholestatic (CLD), and hepatocellular liver disease (HLD); determined the relationship between Child's class and prevalence of peritonitis; and assessed ascitic total protein as a risk factor for peritonitis. Between January 1989 and April 1991, 113 consecutive patients were admitted with chronic liver disease and ascites (49, ALD; 22, CLD; and 42, HLD). All had admission paracentesis. SBP was defined as polymorphonuclear cell count (PMN) > or = 250 mm3 with a positive culture, BA as PMN < 250/mm3 and positive culture, and CNNA as PMN > or = 250/mm3 with negative culture. No patients with obvious intraabdominal source for infection (i.e., secondary peritonitis) were included in the analysis. The prevalence of peritonitis was 8/113 (7%); four patients had SBP, one BA, and three CNNA. The occurrence of peritonitis was independent of the type of liver disease (ALD, 8%; CLD, 9%; HDL, 5%). Neither ascitic fluid total protein nor the severity of liver disease (Child's class) predicted the occurrence of peritonitis. We conclude that the occurrence of peritonitis is unrelated to the type of liver disease, and severity of liver disease did not predict the presence of peritonitis. Also, ascitic fluid total protein < 1.0 g/dl may not be a sensitive predictor of risk of peritonitis.

Ascitic Fluid↗
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↗