Biomedical subjects

Brian J McMahon

Publications and source records attributed to Brian J McMahon.

At least 19 recordsLinked to original sources

PubMed2006

The relationship between previous fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection.

The relationship between prior fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance was associated with any prior fluoroquinolone use over the previous 10 years and with the total number of fluoroquinolone courses prescribed (P<.001).

Adult↗

PubMed2006

Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F.

BACKGROUND: The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has been associated with specific HBV genotypes and the presence of specific mutations. METHODS: From a cohort of Alaska Native people with chronic HBV infection, we genotyped 47 patients with HCC and 1129 patients without HCC, and we tested patients with HCC and control patients for mutations in the basal core promoter and precore regions. RESULTS: Genotype F was found in 68% of patients with HCC, versus 18% of those without HCC (P<.001). For patients with genotype F, the median age at diagnosis of HCC was lower than that for patients with other genotypes (22.5 vs. 60 years, respectively; P=.002). Overall, there were no significant differences in the number of basal core promoter and precore region mutations between patients with HCC and control patients. CONCLUSIONS: We found a significant association between genotype F and the development of HCC among Alaska Native people with chronic HBV infection but no significant association between HCC and basal core promoter or precore mutations in genotype F.

Adolescent↗

PubMed2006

Dynamics of Helicobacter pylori-specific immunoglobulin G for 2 years after successful eradication of Helicobacter pylori infection in an American Indian and Alaska Native population.

Helicobacter pylori antibodies were measured over 24 months in American Indian and Alaska Native persons who cleared their infections. Two months after treatment, 82% of H. pylori-negative persons remained seropositive. While there were declines in H. pylori antibodies for 12 months, after 24 months 71% of persons remained seropositive.

Alaska↗

PubMed2006

High rate of spontaneous negativity for hepatitis C virus RNA after establishment of chronic infection in Alaska Natives.

BACKGROUND: Hepatitis C virus (HCV) leads to chronic infection in 70%-85% of exposed patients. Spontaneous clearance of the virus after chronic infection is believed to occur rarely. METHODS: Alaska Natives who tested positive for HCV antibodies were enrolled in a prospective study that began in 1994 and were followed up on a regular basis. Individuals who tested positive for HCV RNA on 3 separate dates, each of which were at least 1 year apart, were included. Being negative for the virus was defined as having at least 1 negative HCV RNA test result after chronic viremia had been established. RESULTS: Of the 815 patients enrolled in the cohort, 139 met entry criteria and were observed for a mean period of 7.0 years. Eleven (8%) of the persons had at least 1 test in which HCV RNA was undetectable; 7 were classified as having either possible or probable clearance of the virus, corresponding to an annualized clearance rate of 0.74% per person-year (95% CI, 0.30%-1.53%). Of 9 patients who underwent subsequent HCV RNA testing, 5 (56%) had negative test results. A low HCV RNA level was significantly associated with spontaneous nondetectability of HCV RNA. CONCLUSION: Spontaneous HCV RNA negativity during chronic HCV infection is a surprisingly frequent event and is associated with low HCV RNA titers. Knowledge of immunologic determinants of clearance may open up avenues of novel therapy.

Adult↗

PubMed2006

Hepatitis C infection in Alaska Natives with persistently normal, persistently elevated or fluctuating alanine aminotransferase levels.

BACKGROUND/AIMS: An estimated one-third of patients with chronic hepatitis C virus (HCV) infection have persistently normal alanine transaminase (PNALT); however, in many previous studies alanine aminotransferase (ALT) levels were followed for < or = 12 months. METHODS: We analyzed data from a population-based cohort of 935 Alaska Natives with HCV, recruited from 1994 to 2005, to determine the proportion of persons with PNALT, persistently elevated ALT (PEALT), and fluctuating ALT (FLUXALT) to determine factors for each ALT state. We selected persons with two positive HCV RNA results > or = 1 year apart and > or = 6 ALT levels measured over the subsequent 3 years with at least 1 month between ALT measurements (n = 265). We defined a person as having PNALT, PEALT, or FLUXALT when all six ALT levels were normal, elevated, or did not fit either of the above two categories, respectively, during the 3-year follow-up period. RESULTS: Among 208 persistently HCV RNA-positive persons, 13 had PNALT, 121 PEALT, 74 FLUXALT. Among 77 persons who underwent liver biopsy, those with PEALT were more likely to have Ishak fibrosis scores > 2 compared with persons with FLUXALT (44% vs. 10%, OR 7.0, 95% CI: 1.5-33.2). No statistically significant differences were found in ALT classification by age, gender, infection duration, median body mass index, alcohol consumption, residence, risk behavior, RNA level, or genotype. CONCLUSIONS: Only 6% of persons with chronic HCV had PNALT. Persons with PEALT were significantly more likely to have higher fibrosis scores on liver biopsy than those with FLUXALT. Previous studies with short follow-up periods may have overestimated the proportion of persons with normal ALT levels.

Adult↗

PubMed2006

Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999-2003.

BACKGROUND: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. MATERIALS AND METHODS: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution. RESULTS: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p < .01) and clarithromycin resistance (p = .05). CONCLUSIONS: Resistance to metronidazole and clarithromycin is more common among H. pylori isolates from Alaska Native persons when compared with those from elsewhere in the USA.

Adult↗

PubMed2006

Selecting appropriate management strategies for chronic hepatitis B: who to treat.

BACKGROUND: Hepatitis B virus (HBV) infection is a significant problem. In the United States estimates indicate that 0.3% of the population (1.25 million individuals) have chronic hepatitis B infection. METHODS: Review of published practice guidelines and literature on management of hepatitis B to determine: 1) Which persons in Western populations are at the highest risk for HBV infection and should be screened for HBV seromarkers to identify those who are chronically infected and those who need to be protected with hepatitis B vaccine; 2) The importance of regular monitoring in persons with chronic hepatitis B, the frequency of monitoring, and which tests should be performed; 3) How to identify the patients who are appropriate candidates for antiviral therapy. RESULTS: Recommendations for screening, diagnosis, monitoring, and treatment of chronic HBV infection are reviewed. Important differences are discussed between the Practice Guidelines for chronic hepatitis B developed by the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver (APASL). In addition, this article reviews which patients who are no covered by these Guidelines might be candidates for antiviral therapy. DISCUSSION: Established practice guidelines provide direction to providers for the diagnosis and management of chronic HBV infection to reduce the risk of serious sequelae. However, not all patients with chronic hepatitis B are identified, and many of those who are diagnosed do not receive adequate management and follow-up.

Antiviral Agents↗

PubMed2006

Steatosis and hepatitis C in an Alaska Native/American Indian population.

OBJECTIVES: To determine the prevalence and characteristics of steatosis in Alaska Natives/American Indians (AN/AI) with chronic hepatitis C virus (HCV) infection. STUDY DESIGN: This outcomes study began in 1994, and 988 AN/AI have been enrolled, including 222 study patients with a positive HCV RNA who underwent liver biopsy. METHODS: Study patients were analyzed for sex, age at biopsy, estimated length of infection, body mass index (BMI), genotype, ethanol use, HCV RNA and alanine aminotransferase levels. A pathologist blinded to patient identity and clinical data reviewed all biopsy slides for histologic activity and fibrosis. RESULTS: Moderate to severe steatosis was found significantly more often in genotype 3 than in genotypes 1 and 2 (p = 0.008). On multivariate analysis, BMI > 30 and Ishak fibrosis score > or = 2 were significantly associated with steatosis (p = 0.0013 and 0.0002, respectively), but only genotype 3 was associated with presence of moderate to severe steatosis (p = 0.008). CONCLUSIONS: Our findings in a cohort of AN/AI are consistent with results of previous studies in other groups that steatosis is associated with fibrosis in HCV and infection with genotype 3 is associated with more severe steatosis.

Adult↗

PubMed2005

Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up.

BACKGROUND: The duration of protection afforded by hepatitis B vaccination is unknown. OBJECTIVE: To determine antibody persistence and protection from hepatitis B virus (HBV) infection. DESIGN: Prospective cohort study. SETTING: 15 villages in southwest Alaska. PARTICIPANTS: 1578 Alaska Natives vaccinated at age 6 months or older. INTERVENTION: During 1981-1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years. MEASUREMENTS: Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants. RESULTS: Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV. LIMITATIONS: The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up. CONCLUSIONS: Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.

Adolescent↗

PubMed2005

Epidemiology and natural history of hepatitis B.

Hepatitis B virus (HBV) is a common viral pathogen that currently infects an estimated 4 million people worldwide, including 400 million who have chronic infection. Persons with chronic HBV infection are at a lifelong risk of developing hepatocellular carcinoma (HCC) or cirrhosis, or both. Many persons with HBV are unaware that they carry the infection, and, of those who are chronically infected, only a minority receives routine, scheduled follow-up to monitor their disease status. Persons from high-risk populations, especially immigrants from nations where hepatitis B is highly endemic, should be tested for HBV seromarkers and should be vaccinated if they are found to be negative. The natural history of chronic HBV is a dynamic one: patients can fluctuate between periods of active liver inflammation and periods of inactive disease. Disease progression is influenced by various factors, including viral genotype and specific mutations, demographic features, concurrent viral infections, and social and environmental factors. Recent data suggest that antiviral therapy can decrease the risk of liver decompensation and liver-related death and reduce the risk of HCC in selected individuals with active liver disease and severe fibrosis. Persons identified with chronic HBV infection need lifelong, regular monitoring for the development of active liver disease and HCC.

Carcinoma, Hepatocellular↗

PubMed2005

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth.

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.

Age Factors↗

PubMed2005

Results of a hepatitis C general transfusion lookback program for patients who received blood products before July 1992.

BACKGROUND: The Centers for Disease Control and Prevention recommend hepatitis C virus (HCV) antibody (anti-HCV) screening for persons who received blood products before July 1992. A general transfusion lookback program was implemented to identify, counsel, and screen persons who received transfusions at the Alaska Native Medical Center between January 1980 and July 1992. STUDY DESIGN AND METHODS: Hard-copy transfusion records data were entered, and available databases were queried to identify deceased patients and the mailing address of those living. Patients were notified by letter of their HCV risk and encouraged to seek counseling and testing. Serum samples were screened for anti-HCV and HCV RNA, and program costs were estimated. RESULTS: Overall, 3169 transfusion recipients were identified, with 1356 (43%) living and targeted for notification. Of 764 patients notified and screened by this program, 41 (5%) were anti-HCV-positive and 19 (2%) were HCV RNA-positive. There was a higher probability of detecting anti-HCV with each subsequent increase of a transfusion event. Among 298 lookback patients, 33 percent were unaware of having received a blood transfusion. The estimated cost per person sent notification was US$57 and to detect an anti-HCV-positive case it was US$3146. CONCLUSION: This general transfusion lookback program successfully notified and screened patients at a reasonable cost. Further investigation would be helpful in determining the role these programs or other measures could play in promoting HCV screening in persons receiving transfusions before July 1992, especially among those who are unaware of their transfusion history.

Alaska↗

PubMed2005

Evaluation of seaFAST, a rapid fluorescent in situ hybridization test, for detection of Helicobacter pylori and resistance to clarithromycin in paraffin-embedded biopsy sections.

A commercially available rapid fluorescent in situ hybridization (FISH) test, (seaFAST H. pylori Combi-Kit; SeaPro Theranostics International, Lelystad, The Netherlands) was used to simultaneously detect the presence of Helicobacter pylori and determine clarithromycin susceptibility in paraffin-embedded biopsy sections. The FISH method was found to be 97% sensitive, 94% specific for the detection of H. pylori and comparable to agar dilution for the detection of resistance to clarithromycin.

Anti-Bacterial Agents↗

PubMed2004

Epidemiology and risk factors for hepatitis C in Alaska Natives.

Large cohorts of persons infected with hepatitis C virus (HCV) that include patients with multiple risk exposures and behaviors have been rarely reported. We herein describe a population-based cohort of 759 Alaska Natives (AN) with HCV who were recruited into a long-term follow-up study. History of injection drug use (IDU) was reported by 60.1% and blood transfusion by 14.0%. The most common genotype was 1a (42.0%), followed by 1b (20.3%), 2b (14.7%), 3a (14.3%), and 2a (7.8%). By multivariable analysis, risk exposures (blood transfusion vs. other; P < 0.01; odds ratio [OR], 2.87; 95% confidence interval [CI], 1.51-5.45) and year of infection (P < 0.01; OR, 3.47; 95% CI, 1.34-8.96) were significantly associated with HCV RNA-positivity. Having an RNA concentration >/=2 million copies/mL was associated with male gender (OR, 1.94) and genotype (P < 0.01 overall; 1a vs. 3a: OR, 1.92; 2b vs. 3a: OR, 3.17) by multivariable analysis. In conclusion, the two principal risk exposures for AN infected with HCV (IDU and blood transfusion) are the same as the overall U.S. population. Persons with a history of blood transfusion were more likely to be HCV RNA positive than those without such history. Higher RNA levels found in males may explain the more severe disease previously reported in this group.

Adult↗

PubMed2004

Chronic hepatitis B: update of recommendations.

Explore the source record for details and available documents.

Hepatitis B, Chronic↗

PubMed2004

The natural history of chronic hepatitis B virus infection.

Three stages of chronic hepatitis B virus (HBV) infection are recognized: the immune tolerant phase, the chronic hepatitis B phase, and the inactive hepatitis B carrier phase. Active liver disease is most often found in persons with elevated aminotransferase levels and HBV DNA levels >10(5) copies/mL. Possible risk factors for developing liver disease include older age, male gender, presence of hepatitis B e antigen (HBeAg), HBV genotype, mutations in the precore and core promoter regions of the viral genome, and coinfection with hepatitis D (delta) virus. All persons chronically infected with HBV should be followed every 6 to 12 months with aminotransferase levels. Those with elevated levels should be tested for HBeAg and its antibody (anti-HBe) as well as HBV DNA levels to determine if they are in need of further evaluation with a liver biopsy and are candidates for antiviral therapy. Future research will help clarify the outcome of chronic HBV infection.

Alanine Transaminase↗

PubMed2004

Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth.

BACKGROUND: The duration of protection after hepatitis B vaccination of infants is unknown. METHODS: We determined antibody to hepatitis B surface antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B surface antigen (HBsAg)-positive mothers. RESULTS: Of low risk infants receiving a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was unknown and 24% (4 of 17) who had initially responded retained protective titers (> or = 10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12), respectively, responded to a booster dose. In children of HBsAg-positive mothers, 31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with nonprotective titers responded to a booster. In low risk children initially receiving a recombinant vaccine, 12.5% (26 of 208) and none (0 of 36) retained protective anti-HBs titers at 5 and 7 years of age, respectively. Of those who did not have protective titers, 90% (120 of 134) and 91% (32 of 35), respectively, responded to a booster. CONCLUSIONS: Anti-HBs disappeared by 5 years of age in most children who were vaccinated with hepatitis B vaccine from birth. Although most children showed immunologic memory, one-third failed to demonstrate an anamnestic response to a booster dose. Additional long term studies of low risk infants are needed to determine duration of protection and the necessity for or timing of booster doses.

Alaska↗

PubMed2004

Estimating the date of hepatitis C virus infection from patient interviews and antibody tests on stored sera.

OBJECTIVES: Studies on the natural history and outcome of chronic hepatitis C virus (HCV) infection differ regarding the proportion of persons who develop serious sequelae over time. Most of these studies use an estimated date of HCV infection based on risk factor data obtained from patient interviews. The date of HCV infection is often estimated using the year of a pre-1992 blood transfusion (BT), or the first year of injecting drug use (IDU). We sought to determine the accuracy of these dates obtained by interview. METHODS: We compared BT dates reported by patients in a long-term HCV outcome study to dates confirmed in a BT-Lookback project, and also compared the reported first year of IDU to seroconversion dates estimated from HCV tests on historical sera. RESULTS: Of 28 BT recipients who were interviewed in the HCV outcome study and identified in the Lookback project, 14 (50%; 95% CI: 31-69%) were unaware they had received a BT. Of 25 persons identified in the BT-Lookback project with historical sera available, 9 (36%; 95% CI: 19-57%) had anti-HCV results that did not correlate with their confirmed BT date. Of 216 persons with a history of IDU and historical serum samples available, 66 (31%; 95% CI: 25-37%) had anti-HCV results that did not correlate with their reported first year of IDU. CONCLUSIONS: Inaccuracies in the length of HCV could occur in outcome studies that rely on patient recall of risk-factor history. Statistical methods that incorporate the uncertainty in assigning infection date are needed.

Adolescent↗