Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC

BACKGROUND: Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are reported to have the best outcomes after liver transplantation. Based on excellent 5-yr survival results after transplantation, it has been suggested that PSC patients may benefit from "preemptive" transplantation to reduce the risk of cholangiocarcinoma. In this study, we compared 10-yr survival of patients with PSC and PBC using a large database after adjusting for other confounding risk factors. METHODS: The United Network for Organ Sharing (UNOS) database of all patients who had liver transplantation from 1987 to 2001 was used for analysis after excluding patients with multiple organ transplantation, children, and incomplete data. RESULTS: Patients with PSC (n = 3,309) were younger than those with PBC (n = 3,254). Retransplantation rate was high in PSC (12.4%vs 8.5%; p< 0.01), and PSC was an independent predictor for retransplantation on multivariate analysis. Cox regression analysis showed that PSC patients had significantly lower graft and patient survival compared to PBC patients after adjusting for other risk factors. Lower survival in PSC became apparent 7 yr after transplantation. CONCLUSIONS: Patients with PSC had a higher retransplantation rate and lower survival when compared to PBC. Based on this analysis, we do not recommend preemptive liver transplantation for patients with PSC.     

Interferon-β-related DNA on human chromosome 4

A DNA subclone (pPE-4000) derived from the B4 interferon--related human genomic DNA clone was used as a probe in blot-hybridization experiments of DNA from a panel of human-rodent somatic cell hybrids containing overlapping subsets of human chromosomes. The DNA hybridization experiments showed that the B4 IFN- locus is localized to human chromosome 4. A provisional regional assignment to 4q12-qter was also obtained. Thus available hybridization data implicate human chromosomes 2, 4, and 9 in the human IFN- system while the available biological data also implicated human chromosome 5.     

Frequency of Helicobacter pylori and CagA Antibody in Patients with Gastric Neoplasms and Controls: The Indian Enigma

Background Despite association between H. pylori and gastric neoplasm (GN) from the developed world, studies from India, where infection is more common and acquired early, are scant and contradictory. Methods Two hundred and seventy-nine patients with GN from two northern and one eastern Indian centers during the period 1997–2005, 101 non-ulcer dyspepsia (NUD), and 355 healthy volunteers (HV) were evaluated for H. pylori [rapid urease test (RUT), histology and anti-H. pylori, and CagA IgG serology]. Results Patients with GN [263 gastric carcinoma and 16 (6%) primary gastric lymphoma, 208 male] were older than HV (n = 355, 188 male) and NUD (n = 101, 54 male) patients (53 ± 12 versus 44 ± 17 and 43 ± 13 years, respectively; P < 0.001). Eastern Indian patients with GN (n = 145) were younger than those from northern India (n = 134; 52 ± 12 versus 55 ± 12 years; P < 0.007, t-test). In GN and NUD patients H. pylori positivity by RUT [86/225 (38%) versus 46/101 (46%)], anti-H. pylori IgG [154/198 (78%) versus 85/101 (84%)], and histology [136/213 (64%) versus 55/101 (55%)] were comparable (χ ²-test). Serum IgG anti-H. pylori antibody was more common among HV than among GN patients [300/355 (85%) versus 154/198 (78%); P = 0.04, χ ²-test]. Intestinal metaplasia was more common in GN than in NUD patients [101/252 (40%) versus 2/98 (2%), P < 0.000, χ ²-test]. CagAIgG was more common in GN than in NUD patients [124/163 (76%) versus 64/101 (63%)] but comparable to that in HV patients [87/98 (89%), P = NS]. Conclusion Frequency of H. pylori as detected using endoscopy and serology-based tests is not higher among patients with GN as compared with controls in India.     

Prevalence and Clinical Differentiation of Dengue Fever in Children in Northern India

Study  Although an increasing trend in outbreaks of dengue infection is seen in the northern Indian plains, the importance of dengue infection as a cause of acute undifferentiated febrile illness (AUFI) round the year is not known and the validity of clinical signs and simple laboratory parameters in differentiating dengue from other causes of AUFI has been sparsely reported. Objectives  To study the prevalence of dengue infection as a cause of AUFI seen round the year and validity of clinical and simple laboratory features for its diagnosis. Methods  Consecutive children between 6 months and 12 years of age presenting to outpatients on 3 predecided weekdays with complaints of fever of 15 days or less duration and having no localizing signs of infection were enrolled over a 1-year period. Blood counts, liver function tests and ELISA test for dengue IgM were performed besides other investigations. Those testing positive for IgM were considered “probable dengue” (PD) while those with negative IgM tested after 5 days of illness were considered “nondengue” (ND). Clinico-laboratory features were compared between PD and ND. A randomly selected subsample of IgM +ves was tested for dengue genome by real time PCR assay. Results  Of 298 children enrolled over 1 year, 56 (18.8%) tested positive for dengue IgM and 132 were ND. Comparing PD and ND, age, duration of illness at presentation, rash, bleeding manifestations, vomiting, platelet count, liver transaminases, serum proteins, albumen and bilirubin were significant features on univariate analysis. On logistic regression younger age, rash and higher serum alanine transaminase (sALT) levels were the only significant independent predictors for PD. Taking cutoff of age as 60 months or less and sALT > 40 units, one or more of these features were seen in 50/56 PD cases (sensitivity 89.3%). All of these were present in only 1 of 132 ND cases (specificity 99.2%). Randomly selected 44 of the 56 IgM +ve patients were subjected to PCR assay, of which 15 were positive. Conclusions  Dengue transmission occurs round the year in this region. The cause of AUFI was definitely dengue in 15/298, i.e., 5% cases and likely to be dengue in another 13.8% cases. In children presenting to outpatients here with AUFI, young age, rash, and raised sALT are significant independent pointers to dengue. A combination of clinical and laboratory features including liver enzymes could be used to achieve high sensitivity and specificity. These results should be validated in a separate data set.     

The effectiveness of long-acting penicillin (penidur) in preventing recurrences of dermatolymphangioadenitis(DLA) and controlling skin, deep tissues, and lymph bacterial flora in patients with "filarial" lymphedema

Dermatolymphangioadenitis (DLA) is a common and serious complication of so-called "filarial" and bacterial non-filarial lymphedema of the limb, affecting skin, lymphatics and lymph nodes. In our previous studies, we demonstrated that more than 60% of patients revealed presence of bacterial isolates in deep tissues, tissue fluid and lymph from the lymphedematous limbs. The question remained open whether elimination or suppression of bacteria dwelling in lymphedematous tissues by administration of low doses of penicillin for long time periods would prevent recurrence of DLA attacks. In this study, we retrospectively evaluated a self/community-selected group of patients with lymphedema of the lower limbs with respect to the efficacy of long-acting penicillin in preventing episodes of DLA. There were no microfilariae or anti-filarial antibodies detected in the investigated group. The questions we asked were: (a) how effective is the benzathine penicillin in preventing recurrences of DLA attacks and (b) how does its long-term administration influence the bacterial spectrum of leg skin, deep tissues, lymph and lymph nodes and sensitivity to antibiotics. Two randomly selected groups of patients, receiving and not receiving penicillin during the same period of time, were compared. Evidently lower recurrence rate of DLA was observed in the treated group (p < 0.002). There was increased prevalence of cocci and gram-positive bacilli with a concomitant decrease of gram-negative bacilli on the foot and calf skin surface. Simultaneously, decreased prevalence of gram-positive cocci and gram-negative bacilli isolates in limb deep tissues and lymph was seen. No resistance to penicillin and other tested antibiotics developed in isolates from the skin surface, deep tissues and lymph. We conclude that long-lasting penicillin is effective in preventing recurrent DLA attacks.     

Preference-weighted health-related quality of life measures and substance use disorder severity

Aims   Examine the validity of preference-weighted health-related quality of life measures in a sample of substance use disorder (SUD) patients. The implications of cost–utility analyses (CUAs) of SUD interventions are discussed.
Design   Cross-sectional analysis of subjects seeking SUD treatment.
Setting   Seven SUD treatment centers in a medium-sized Midwestern metropolitan area in the United States.
Participants   Data from 574 SUD subjects were analyzed from a study to test interventions to improve linkage and engagement with substance abuse treatment.
Measurements   Subjects completed the following preference-weighted measures: self-administered Quality of Well-Being scale (QWB-SA) and Medical Outcomes Study SF-12 (standard gamble weighted or SF-12 SG); and clinical measures: Addiction Severity Index (ASI) and a symptom checklist based on the DSM-IV.
Findings   In unadjusted analyses, the QWB-SA was correlated significantly with six of seven ASI subscales and the SF-12 SG was correlated with four of seven. In adjusted analyses, both preference-weighted measures were significantly correlated with diagnostic, physical health, mental health and drug use measures, but not with legal or alcohol use measures. The QWB-SA was also correlated with employment problems and the SF-12 SG was correlated with family/social problems.
Conclusions   This study generally supports the construct validity of preference-weighted health-related quality of life measures in SUD patients. However, the QWB-SA and SF-12 SG did not correlate with all ASI scales. Cost–benefit analysis may be preferable when policy-makers are interested in evaluating the full range of SUD intervention outcomes.     

Acute hepatitis C

Symptomatic acute hepatitis C occurs in only about 15% of patients who are infected with hepatitis C virus (HCV). Acute hepatitis C is most often diagnosed in the setting of post-exposure surveillance, or seroconversion in high-risk individuals (eg, health-care professionals or injecting drug users) previously known to be seronegative. Although transmission via transfusion and injecting drug use has declined in developed countries, unsafe blood products and medical practices continue to increase transmission of HCV in many developing countries. Clinically, acute hepatitis C can increase concentrations of alanine aminotransferase to ten times the upper limit of normal but almost never causes fulminant hepatic failure. Diagnosis of HCV infection in the acute phase is difficult since production of antibodies against HCV can be delayed by up to 12 weeks, and about a third of infected individuals might not have detectable antibody at the onset of symptoms. Therefore, testing for HCV RNA by PCR is the only reliable test for the diagnosis of acute infection. Symptomatic patients with jaundice have a higher likelihood of spontaneous viral clearance than do asymptomatic patients, and thus should be monitored for at least 12 weeks before initiating antiviral therapy. By contrast, asymptomatic patients have a much lower chance of spontaneous clearance, and might benefit from early antiviral therapy. Antiviral therapy for 12 weeks is generally effective in treating patients who are HCV RNA negative after 4 weeks of treatment; lengthier courses could be needed for those who relapse or fail to show early virological clearance.     

Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain

Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP(+) cells does so, prompting the question of whether the proliferating GFAP(+) cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP(+) cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the platelet-derived growth factor (PDGFRalpha) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.     

Patients with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection have less severe gastroesophageal reflux disease: a study using endoscopy, 24-hour gastric and esophageal pH metry

Background and aim  

The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion.     

Endocrine diseases and the liver

Liver disease and endocrine disorders, both common in the general population, have a bidirectional and complex relationship. Certain liver diseases are more commonly associated with endocrine disorders, including nonalcoholic fatty liver disease, autoimmune hepatitis, and primary biliary cirrhosis. There may be an association between hepatitis C and type 2 diabetes mellitus as well as thyroid disorders, and sex hormonal preparations may cause specific hepatic lesions. The presence of relative adrenal insufficiency in patients with end-stage liver disease may have therapeutic implications in patients admitted with acute-on-chronic liver failure. The objective of this review is to focus on the effect of endocrine disorders on liver.