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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 271 records · Page 15Linked to original sources
PubMed1998

Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure.

BACKGROUND/AIMS: High levels of tumor necrosis factor-alpha are associated with an increased risk of severe encephalopathy in acute liver failure, and experimental studies suggest that tumor necrosis factor-alpha plays a role in the development of acetaminophen (paracetamol)-induced liver injury and associated multiple organ failure. Inter-individual variations in the production of tumor necrosis factor-alpha have been linked to genomic polymorphisms within the tumor necrosis factor-alpha locus. This study examined whether specific tumor necrosis factor polymorphisms are associated with variations in the severity of clinical features in acetaminophen-induced acute liver failure. METHODS: Genotypes at the -308 tumor necrosis factor A and tumor necrosis factor B Nco1 polymorphic sites were determined in 97 patients with severe acetaminophen-induced hepatotoxicity and 109 controls, using polymerase chain reaction and restriction fragment length polymorphism. The relationship between liver injury, multiple organ failure and encephalopathy, determined retrospectively from clinical notes and genotype, was examined. RESULTS: No significant association was found between either tumor necrosis factor A or B genotype and parameters for multiple organ failure or liver injury. The tumor necrosis factor B1B1 genotype was significantly under-represented in those patients developing severe encephalopathy (p=0.03) and a multivariate logistic regression analysis confirmed the influence of tumor necrosis factor B genotype (p<0.01). The association was independent of the HLA class II allele DRB1*03, which is closely linked to the TNFB locus. CONCLUSIONS: The development of acute liver failure is unlikely to be primarily sepsis driven. However, the apparent protective effect of the tumor necrosis factor B1B1 genotype on the development of severe encephalopathy may be related to the effects of this genotype on tumor necrosis factor-alpha production in sepsis.

APACHE↗
PubMed1998

Mycobacterial DNA not detected in liver sections from patients with primary biliary cirrhosis.

BACKGROUND/AIMS: Recent studies in primary biliary cirrhosis have reported the detection of serum antibodies against Mycobacterium gordonae and of mycobacterial DNA in liver sections. The aim of this study was to investigate whether mycobacterial DNA is present in liver biopsy material in primary biliary cirrhosis. METHODS: Archival liver biopsy specimens from 11 patients with primary biliary cirrhosis (10 female, mean age 52 years) and 11 patients with autoimmune hepatitis (10 female, mean age 53 years) were identified. Positive control tissue comprised five archival lymph node specimens from patients with tuberculous lymphadenopathy, three of which had stained positive on ZN staining, and also a liver biopsy specimen from a patient with tuberculous hepatitis (ZN positive). Fixed sections were deparaffinised and DNA was extracted by mechanical disruption with glass beads. DNA was purified by use of diatoms and lysis in guanidinium thiocyanate in a technique previously validated for archival DNA. Primers were directed to amplify a partial 16S ribosomal RNA gene yielding the species-specific character for mycobacteria, and also to amplify the constitutively-expressed human gene GAPDH. RESULTS: The polymerase chain reaction was shown to be capable of detecting 1 fg of M. gordonae DNA in 'spiked' samples, equivalent to 1-5 bacterial cells. No mycobacterial DNA was detected in liver biopsy samples from either the primary biliary cirrhosis or autoimmune hepatitis groups. Of the tuberculous control sections, mycobacterial DNA was detected in four of five lymph nodes and the liver biopsy specimen. GAPDH amplification was detected in all tested samples from liver disease and tuberculous control samples. CONCLUSION: These data do not support a role for mycobacteria in the aetiology of primary biliary cirrhosis.

Adult↗
PubMed1998

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

BACKGROUND/AIMS: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. METHODS: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. RESULTS: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). CONCLUSIONS: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Adult↗
PubMed1998

Social class and health: the puzzling counter-example of British South Asians.

British South Asians (with ancestry from the Indian subcontinent) provided a puzzling exception to the British class gradient in mortality during the 1970s. On the assumption that class gradients in health are produced mainly by gradients in standard of living, this might be due to a break in the relation of class to standard of living (change in class structure), or by a break in the relation of standard of living to patterns of health behaviour and health risk (change in class lifestyles). Data on these characteristics are available from the West of Scotland Twenty-07 Study, where 159 South Asians aged 30-40 (mean age 35) were sampled alongside 319 of the general population in Glasgow. As regards changes in class structure, results indicate that the underclass thesis, which suggests that ethnic minorities are forced into less eligible jobs or into a separate labour market or into unemployment, resulting in a standard of living below that of the general population, still holds good for British South Asians in categories from social class III non-manual downwards. It does not hold good for owners of small businesses, where Sikhs and Hindus in particular have a standard of living equivalent to general population counterparts. However, prosperity is not predictable from levels of education in the subcontinent and from this and other signs it appears that a wholesale redistribution of class chances is occurring among British South Asians, disrupting inter-and intra-generational continuities in the relation between class and standard of living. There is little sign of change in class lifestyles, i.e. in the relation between standard of living and health behaviour or health risk. As yet, though, the new distribution of standard of living is affecting patterns of health behaviour and health risk more strongly than symptom experience or chronic illness, suggesting that a class gradient in health will re-emerge.

Adult↗
PubMed1998

Ventricular remodelling and revascularization in severe left ventricular dysfunction.

OBJECTIVE: To evaluate the role of surgical revascularization in the presence of severe, global impairment of left ventricular function without discrete aneurysm formation or mitral regurgitation. The high mortality and morbidity associated with this group, together with the limited benefits tend to prompt referral for cardiac transplantation. METHODS: Fifty-three patients initially referred for transplantation, in addition to coronary revascularization, underwent mitral annuloplasty (group A = 23), free wall remodelling by endoaneurysmorrhaphy (group B = 17) or mitral annuloplasty and free wall reconstruction (group C = 13). The mean ages were 59, 56 and 57 years for groups A, B and C, respectively. Detailed assessment of pre- and post-operative physical and psychological status were carried out. RESULTS: Follow-up was for a mean period of 22-26 months. All patients reported substantial improvement in quality of life, both physical and psychological parameters and in NYHA functional class status. Objective evidence of improvement in ejection fraction was seen in all three groups but especially in group A. There were five early deaths, four were due to inadequate revascularization due to the poor quality of target vessels. There were three late deaths and one patient that required transplantation. CONCLUSION: We conclude that patients with severe left ventricular dysfunction can be candidates for surgical revascularization and optimization of ventricular geometry with acceptable mortality. The importance of achieving complete revascularization is emphasized in this series.

Aged↗
PubMed1998

Evaluation of bioequivalence of highly variable drugs using clinical trial simulations. II: Comparison of single and multiple-dose trials using AUC and Cmax.

PURPOSE: Evaluating of the effects of high intrasubject variability in clearance (CL) and volume of distribution (V), on 90% confidence intervals (CIs) for AUC (Area Under the concentration Curve) in single and multiple-dose bioequivalence studies. The main methodology was Monte Carlo simulation, and we also used deterministic simulation, and examination of clinical trials. The results are compared with those previously observed for Cmax (maximum concentration.) METHODS: The time course of drug concentration in plasma was simulated using a one-compartment model with log-normal statistical distributions of intersubject and intrasubject variabilities in the pharmacokinetic parameters. Both immediate-release and prolonged-release products were simulated using several levels of intrasubject variability in single-dose and multiple-dose studies. Simulations of 2000 clinical bioequivalence trials per condition (138 conditions) with 30 subjects in each crossover trial were carried out. Simulated data were compared with data from actual bioequivalence trials. RESULTS: The current simulations for AUC show similar probabilities of failure for single-dose and multiple-dose bioequivalence studies, even with differences in the rate of absorption or fraction absorbed. AUC values from prolonged-release scenario studies are more sensitive to changes in the first order absorption rate constant ka, and to variability in CL and V than AUC from studies of immediate-release studies. CONCLUSIONS: We showed that multiple-dose designs for highly variable drugs do not always reduce intrasubject variability in either AUC or Cmax, although the behavior of AUC differs from Cmax. Single dose AUC to the last quantifiable concentration was more reliable than either single dose AUC extrapolated to infinity, or multiple dose AUC during a steady-state interval. Multiple-dose designs may not be the best solution for assessing bioequivalence of highly variable drugs.

Area Under Curve↗
PubMed1998

Evidence that S-adenosyl-L-methionine diastereoisomers may reduce ischaemia-reperfusion injury by interacting with purinoceptors in isolated rat liver.

1. Mechanisms underlying the haemodynamic activity of diastereoisomers of S-adenosyl-L-methionine (SAM) were investigated using inhibitors of purinoceptors and nitric oxide (NO) synthase in perfused rat livers damaged by sequential 24 h cold and 20 min rewarming ischaemia + reperfusion. 2. Stored livers were flushed with 10 ml saline alone (control) or with added (R,S) or (S,S) SAM (100 microM) and reperfused in the absence (control) or presence of 10 microM 8-phenyltheophylline (8-PT) or 100 microM L-N-monomethylarginine (L-NMMA). 3. Both SAM diastereoisomers rapidly increased blood flow and bile production versus controls (P<0.001) but the (R,S) isomer induced greater increases in blood flow and the (S,S) isomer greater increases in bile production: 625 versus 596 versus 518 ml blood flow and 100 versus 119 versus 56 mg bile production per g liver over 3 h in (R,S), (S,S) and control, respectively. 4. 8-PT prevented the enhancement of blood flow by (S,S) SAM (529 versus 596 ml g(-1) liver over 3 h for (S,S) SAM alone, P<0.001), but was without effect in control livers. 8-PT also reduced SAM-enhanced bile production: 51 versus 119 mg g(-1) liver over 3 h, P<0.001. L-NMMA reduced blood flow and bile production similarly in the absence or presence of (S,S) SAM. 5. Thus, SAM may improve liver perfusion after ischaemia-reperfusion injury via stimulation of P, (A2) purinoceptors at which SAM shows activity. The choleretic activity of (S,S) SAM is disproportionately greater than enhanced blood flow and may occur independently of a NO-dependent component of bile production.

Animals↗
PubMed1998

Somatic mutation of immunoglobulin V(H)6 genes in human infants.

Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated V(H)6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of V(H)6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T-B cell interaction and functional germinal centres, is approaching maturity from 6 months old.

Adult↗
PubMed1998

Plasma cytokine levels and coagulation and complement activation during use of the extracorporeal liver assist device in acute liver failure.

Multiple organ failure frequently occurs in patients with acute liver failure, and this has been associated with increased cytokine production. Treatment by hemoperfusion with an extracorporeal liver assist device (ELAD) containing human liver-derived cells was performed in 12 patients with acute liver failure. Over the first 6 h, there were significant increases in plasma tumor necrosis factor alpha (TNFalpha; from 114+/-54 pg/ml [mean+/-SEM] to 236+/-161 pg/ml, p < 0.05) and interleukin (IL)-6 (260+/-121 pg/ml to 445+/-149 pg/ml, p < 0.05) but not in interferon gamma (IFNgamma). A similar pattern with a small peak increase was observed for complement C5b-9 complex. Plasma C-reactive protein (CRP) and thrombin antithrombin (TAT) III complex showed small peaks after 24 h of ELAD hemoperfusion. No such changes were seen in 12 control patients with acute liver failure who were treated with intensive care alone. These transitory effects, without changes in blood pressure, are likely to be due to the contact of the blood with the dialyzer membrane. There was no evidence of the clearance of cytokines by the ELAD.

Adolescent↗
PubMed1998

Prevalence of traumatic brain injury in psychiatric and non-psychiatric subjects.

Traumatic brain injury (TBI) and its sequelae may impact the expression and treatment of psychiatric disorders. The prevalence of TBI in psychiatric patients is unknown and investigations in the general population are limited. This study examined the prevalence of TBI with loss of consciousness in mental health setting patients (n = 231), general hospital and university staff and students (n = 534) and non-psychiatric medical clinical patients (n = 59). The Traumatic Brain Injury Questionnaire was used to assess TBI. A greater percentage of psychiatric patients reported TBI than medical patients or staff and students. Traumatic brain injuries were typically mild--moderate, medical assistance was frequently sought and use of alcohol and drugs was reported in a minority of TBI incidents. Multiple injuries were most common in psychiatric patients. The percentage of medical patients and staff and students reporting TBI was similar to previous research. The greater percentage of psychiatric patients reporting TBI indicates the need to assess TBI in this population. The role of TBI in the emergence, expression and treatment outcome of psychiatric disorders and the risk factors that leave psychiatric patients vulnerable to TBI should be further examined.

Adult↗
PubMed1998

Clearance of persistent hepatitis B virus infection in Chinese bone marrow transplant recipients whose donors were anti-hepatitis B core- and anti-hepatitis B surface antibody-positive.

Thirteen hepatitis B surface antigen-positive Chinese patients who received hepatitis B surface antibody-positive marrow (hepatitis B core antibody-positive or -negative: 6 and 7, respectively) via allogeneic bone marrow transplantation (BMT) were studied. After BMT, 4 recipients had serologic clearance of hepatitis B surface antigen from hepatitis B core antibody-positive marrow, but none of the recipients of hepatitis B core antibody-negative marrow had serologic clearance (P=.02). There was no significant difference in the donors' hepatitis B surface antibody titer before BMT for patients with or without serologic clearance of hepatitis B surface antigen (2255.2+/-4244.0 vs. 854.2+/-2306.7 mIU/mL; P=not significant). Adoptive immunity clearance of hepatitis B surface antigen was favored by hepatitis B core antibody positive-donor marrow and was not related to donor pre-BMT hepatitis B surface antibody titer.

Adolescent↗
PubMed1998

Tumour ablation and hepatic decompensation rates in multi-agent chemoembolization of hepatocellular carcinoma.

Thirty-seven cirrhotic patients with 62 hepatocellular carcinoma (HCC) foci--most Child-Pugh class B or C and/or with large, inoperable tumours--underwent 148 sessions of transcatheter arterial chemoembolization (TACE) using lipiodol, doxorubicin and cisplatin. Treatment efficacy was assessed by serial hepatic arteriography in 34/37 (91.9%) patients and abdominal CT scanning in 3/37 (8.1%) patients. Child-Pugh status was determined prior to each treatment session. Varying degrees of control of tumour neovascularity occurred for a median 390 days (range 90 to > 1680 days) in 33/34 (97.1%) patients in whom progress hepatic arteriography was performed. Ablation of tumour neovascularity occurred in 6/6 (100%), 4/12 (33.3%) and 6/16 (37.5%) patients with HCC diameters < 4 cm, 4-7 cm and > 8 cm, respectively (p < 0.02). Significantly more sessions were required for ablation of larger tumours (p < 0.05). Recurrent HCC was detected in 50% of patients after a median 240 days (range 60-1120 days). Deterioration in Child-Pugh status followed a session of TACE on 19/148 (12.8%) occasions but resulted in unscheduled hospitalization on only 4/148 (2.7%) occasions, the highest incidence (8.3%) in Child-Pugh C patients. Actuarial survival was 27/36 (75.0%) at 6 months, 17/34 (50.0%) at 12 months, 14/34 (41.2%) at 18 months, 9/31 (29.0%) at 24 months and 4/27 (14.8%) at 36 months. Multi-agent TACE with lipiodol, doxorubicin and cisplatin provides a useful anti-tumour effect, even in cirrhotic patients with large HCCs. The incidence of clinically significant deterioration in hepatic function due to ischaemia of non-tumorous liver is acceptably low, even in Child-Pugh C patients.

Aged↗
PubMed1998

Adult mesoblastic nephroma: expansion of the morphologic spectrum and review of literature.

Mesoblastic nephroma (MN) is a distinctive tumor that is seen mostly in early infancy and that consists of classic and cellular (atypical) variants. Mesoblastic nephroma rarely occurs in adulthood, but MN in this age group still is poorly characterized because there are only 17 reported cases. We describe five additional cases of adult MN, including one case of the cellular variant, characterize the immunohistochemical profiles in detail, and critically review the previously reported cases. The collective data obtained from these 22 cases of adult MN showed that the patients predominantly were women (20 cases), ranging in age from 19 to 78 years, who were asymptomatic (5 cases) or had nonspecific signs and symptoms referable to a renal mass. Twenty tumors were classified as classic and 2 as cellular. The tumors were 2-24 cm, well circumscribed, and partially encapsulated and displayed a solid/ cystic cut surface, with a predominantly solid component in most tumors. One tumor, however, was almost purely cystic. Most tumors extended to the renal sinus. and some appeared entirely intrapelvic on imaging studies; however, gross and microscopic evaluation did not show destructive invasion of the pelvic wall. Extension of the tumor beyond the renal capsule has not been described. Each tumor was composed of epithelial and stromal components both. The epithelial component, which displayed no difference between the classic and cellular variants, was composed of isolated or clustered tubules and cysts lined by a benign epithelium with a wide range of cytologic differentiation. The stromal cells were composed of fibroblasts, myofibroblasts, and smooth muscle cells in various combinations. Stromal cellularity was low for the classic variant but high for the cellular variant. Hemorrhage, necrosis, and high mitotic index were noted in the stroma of the cellular, but not in the classic variant. Immunohistochemical study applied to the five current cases and seven normal control kidneys confirmed the presence of fibroblasts, myofibroblasts, smooth muscle cells, and prominent vessels in the stroma of each tumor. Most cysts and tubules within the tumors had a distinctive immunohistochemical profile, similar to that of collecting duct but different from those of other portions of the nephron in the normal control kidneys. After total or partial nephrectomy, without adjuvant chemotherapy or radiotherapy, 19 patients, including the 2 with cellular MN, were alive and well at 8-months to 48-years follow-up. Follow-up was not available in two patients. The remaining patient had recurrence at the surgical site 24 years after nephrectomy. Adult MN displays a distinctive morphologic spectrum that parallels that of its pediatric congener. It probably is a benign tumor that can be treated successfully by complete excision. The collecting duct differentiation expressed by most tubules and cysts of adult MN implies ureteric bud, which is the exclusive embryologic origin of collecting duct, as an important element in the histogenesis of this rare but fascinating type of tumor.

Adult↗
PubMed1998

Split liver transplantation: King's College Hospital experience.

BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs.

Adolescent↗
PubMed1998

Earlier identification of patients at risk from acetaminophen-induced acute liver failure.

OBJECTIVE: To determine whether the Acute Physiology and Chronic Health Evaluation (APACHE) II system for the measurement of severity of illness is able to provide an accurate risk of hospital death in patients with acetaminophen-induced acute liver failure or identify those patients needing transfer for possible hepatic transplantation. DESIGN: Data for admission (first 24 hrs) APACHE II scores and King's criteria for urgent transplantation were collected prospectively to compare the APACHE II system and the King's criteria for the prediction of death or need for transplantation. SETTING: A nine-bed specialist liver failure unit (LFU). PATIENTS: One hundred two consecutive patients admitted to the LFU with acetaminophen self-poisoning and a prolonged prothrombin time were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An APACHE II score of > 15 points was associated with a high mortality (13/20 patients, five of whom survived following hepatic transplantation). There was no relation between APACHE II risk and outcome (mean APACHE II risk of death 0.8%, actual hospital mortality 16%). An APACHE II score of > 15 had a similar power of prediction of death as the King's criteria (sensitivity 82% and 65%, respectively; specificity 98% and 99%, respectively), when considering those patients who were transplanted as "deaths." An APACHE II score of > 15 was able to identify four more patients than the King's criteria on the first day of admission to the LFU. CONCLUSIONS: The crude admission APACHE II score correlated well with mortality in patients with acetaminophen-induced acute liver failure. However, the calculated APACHE II risk of death, using the original drug overdose coefficient, was poorly calibrated. Since specialist liver scores are unfamiliar in the general intensive care setting, the use of an APACHE II score might earlier identify more patients at risk of needing a liver transplant, and hence, expedite appropriate transfer to a specialist liver unit.

APACHE↗
PubMed1998

A clinical study of hair removal using the long-pulsed ruby laser.

BACKGROUND: Laser hair removal is rapidly becoming a widely used modality. Clinical studies are needed to assess these hair removal systems. The long-pulsed ruby laser is one such modality for the removal of unwanted hair. OBJECTIVES: To evaluate the efficacy of the long-pulsed ruby laser (694 nm, 3-msec pulsewidth, 7- or 10-mm spot size) in removing unwanted hair, and to provide treatment guidelines for the proper utilization of this laser system. METHODS: Forty-eight areas of unwanted facial and body hair from 25 patients with blonde, brown, or black hair were treated with the long-pulsed ruby laser at fluences between 10 and 40 J/cm2. Hair regrowth was measured at 4 weeks after the first treatment, 4 weeks after the second treatment, 4 weeks after the third treatment, and 16 weeks after the third treatment by counting the number of terminal hairs compared with baseline pretreatment values. All complications and treatment outcomes were documented. RESULTS: The mean percent of regrowth after the first treatment was 65.5%, 41% after the second treatment, and 34% after the third treatment. Overall, regardless of skin type or targeted body region, patients who underwent three treatment sessions demonstrated an average 35% regrowth in terminal hair count compared with baseline pretreatment values 6 months after initial therapy. CONCLUSION: Long-pulsed ruby laser treatment resulted in significant hair growth delay in most cases. Repeated laser treatments produced an increased number of vellus hairs, an increase in growth delay, and a decreased percentage of hair regrowth.

Abdomen↗
PubMed1998

Liver damage in human small intestinal bacterial overgrowth.

OBJECTIVE: Some rodent strains with experimental small intestinal bacterial overgrowth (SIBO) unrelated to jejunoileal bypass are susceptible to hepatic damage, possibly because of increased small intestinal permeability to proinflammatory bacterial polymers. However, data on the prevalence of hepatic damage in human subjects with SIBO in this setting are lacking. This study addressed this issue. METHODS: Seventy adult subjects were investigated for possible SIBO and hepatic damage with bacteriological analysis of small intestinal aspirates and measurement of serum concentrations of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, and alanine aminotransferase. Nutritional indices (serum albumin and anthropometry) and the urinary lactulose/mannitol ratio, an index of small intestinal permeability, were measured in all subjects with SIBO and liver damage. RESULTS: SIBO was present in 40 of 70 subjects (57.1%). Overgrowth flora included salivary-type bacteria alone in 11 subjects and colonic-type bacteria in 29 subjects (facultative anaerobes [Enterobacteriaceae] alone in 21 subjects and both facultative and obligate anaerobes [Enterobacteriaceae and Bacteroides spp] in eight subjects). Biochemical evidence of liver damage was found in zero of 30 subjects without SIBO, zero of 11 subjects with SIBO with salivary-type bacteria alone, zero of 21 subjects with SIBO with facultative but not obligate anaerobic colonic-type bacteria, and in one of eight subjects (12.5%) with SIBO with obligate anaerobic colonic-type bacteria, in whom serum alkaline phosphatase and gamma-glutamyl transpeptidase levels were elevated. Nutritional indices were normal in this patient. Small intestinal permeability was increased and, along with liver enzyme abnormalities, normalized after eradication of SIBO. Small intestinal permeability was also increased in three of six patients (50.0%) with SIBO with obligate anaerobic colonic-type bacteria who had no evidence of liver damage. CONCLUSIONS: SIBO per se is not a major risk factor for liver damage in humans, even when the overgrowth flora includes obligate anaerobes. Liver damage is not a necessary consequence of increased small intestinal permeability in this setting.

Adolescent↗