Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India.

Background & objectives: Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Methods: Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. Results: HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. Interpretation & conclusions: HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to initiate appropriate ART regimen.

Effect of drinking arsenic-contaminated water in children.

Chronic arsenic toxicity due to drinking of arsenic-contaminated water has been a major environmental health hazard throughout the world including India. Although a lot of information is available on health effects due to chronic arsenic toxicity in adults, knowledge of such effect on children is scanty. A review of the available literature has been made to highlight the problem in children. Scientific publications on health effects of chronic arsenic toxicity in children with special reference to psychological issues are reviewed. The prevalence of skin abnormalities such as pigmentation change and keratosis, the diagnostic signs of chronic arsenic toxicity, vary in various arsenic-exposed children population in different regions of the world. The occurrence of chronic lung disease including pulmonary interstitial fibrosis has been described in arsenic-exposed children in Chile. Affection of intellectual function has also been reported to occur in arsenic-exposed children studied in Thailand, Bangladesh, and India. Methylation patterns of arsenic in children aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Chronic arsenic toxicity due to drinking of arsenic-contaminated water causes significant morbidity in children resulting in skin lesions, lung disease, and defect in intellectual function.

Systemic manifestations in chronic arsenic toxicity in absence of skin lesions in West Bengal.

BACKGROUND & OBJECTIVE: Pigmentation and keratosis are the prerequisites to diagnose arsenicosis. However, many systemic manifestations occur in association with pigmentation and keratosis in people exposed to chronic drinking of arsenic contaminated water. The present study aim to find out whether systemic manifestations occur in significant number of cases in arsenic exposed people in the absence of skin lesions in an affected district in West Bengal, India. METHODS: A cross-sectional study was carried out in South 24 Parganas, an arsenic affected district of West Bengal, India. Both dermatological and systemic manifestations were recorded and water samples collected for arsenic analysis from 7683 participants. A correlation of systemic manifestations in relation to arsenic exposure was carried out in subjects having no arsenical skin lesion. Prevalence odds ratio (POR) was calculated for each outcome comparing those with high arsenic exposure with those with lowest exposure. RESULTS: The frequency of occurrence of various clinical manifestations like weakness, anaemia, diarrhoea, hepatomegaly and lung disease was found to be significantly higher among participants drinking water having arsenic concentration > or = 50 microg/l in comparison to those taking water with arsenic content below this level. Further, there was increased occurrence of these manifestations with increasing concentration of arsenic level in drinking water, and this followed a dose-response relationship. INTERPRETATION & CONCLUSION: It appears that it is worthwhile to include people with systemic manifestations in absence of skin lesions with evidence of arsenic exposure as suspected cases of arsenicosis for case detection and in surveillance programme.

Chronic arsenic toxicity & human health.

Chronic arsenic toxicity (arsenicosis) due to drinking of arsenic contaminated ground water is a major environmental health hazard throughout the world including India. A lot of new information is emerging from extensive research on health effects of chronic arsenic toxicity (CAT) in humans during the last two decades. Available literature has been reviewed to highlight the problem including its malignancies. Pigmentation and keratosis are the specific skin lesions characteristics of CAT. CAT also produces various systemic manifestations over and above skin lesions, important ones being chronic lung disease like chronic bronchitis, chronic obstructive pulmonary disease and bronchiectasis, liver disease like non-cirrhotic portal fibrosis and other diseases like polyneuropathy, peripheral vascular disease, hypertension and ischeamic heart disease, diabetes mellitus, non-pitting oedema of feet/hands, weakness and anaemia. Cancer of skin, lung and urinary bladder are important cancers associated with chronic arsenic toxicity. Stoppage of drinking of arsenic contaminated water is the main stay in the management of arsenicosis as specific chelation therapy has limited value. Early skin cancer, detectable by regular active surveillance, is curable. In addition to dermatological features, CAT produces protean clinical manifestations. Treatment of arsenicosis is unsatisfactory and is mostly symtomatic.

Effect of drinking arsenic contaminated water in children.

OBJECTIVE: Chronic arsenic toxicity due to drinking of arsenic contaminated water is a major environmental health hazard throughout the world including India. Though lot of information is available on health effects due to chronic arsenic toxicity in adults, knowledge of such effect on children is scanty. A review of available literature has been made to highlight the problem in children. REVIEW METHODS: Scientific publication in journals, monograph, thesis and proceedings of conferences on arsenic in regard to epidemiological, clinical and psychometric studies were reviewed. RESULTS: Skin abnormalities including pigmentation change and keratosis are the diagnostic signs of chronic arsenic toxicity in adults. Incidence of skin manifestations vary between 1.9-37.1% in various arsenic exposed children populations in different regions of the world. Occurrence of chronic lung disease including pulmonary interstitial fibrosis was described in arsenic exposed children in Chile. Affection of intellectual function is also reported from Thailand, Bangladesh and India. CONCLUSION: Chronic arsenic toxicity due to drinking of arsenic contaminated water causes significant morbidity in children in different parts of the world.

Seasonal variation of arsenic concentrations in tubewells in west Bengal, India.

This study was conducted to monitor the changes in arsenic concentration during different seasons in a one-year period during 2002-2003 in selected tubewells in an arsenic-affected area in the district of South 24 Parganas in West Bengal, India, and to map the location of the wells. Seasonal variations in concentrations of arsenic in water were measured from 74 selected tubewells, ranging in depth from 40 to 500 feet. Water samples were collected from these wells during winter, summer, monsoon, and the following winter in 2002-2003. A global positioning system was used for locating the tubewells, and a geographic information system was used for mapping. There was evidence of seasonal variation in concentrations of arsenic in water (p=0.02) with the minimum average concentration occurring in the summer season (694 microg/L) and the maximum in the monsoon season (906 microg/L). From the winter of 2002 to the winter of 2003, arsenic concentrations increased, irrespective of the depth of the tubewells, from an average of 464 microg/L to 820 microg/L (p<0.001). This extent of variation in arsenic concentration, if confirmed, has important implications for both epidemiological research and mitigation programmes.

Arsenic and liver disease.

The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

Oxidative stress in liver of mice exposed to arsenic-contaminated water.

BACKGROUND: Oxidative stress has been implicated in the initiation of hepatic damage caused by various agents. Not much data on oxidative stress in liver in chronic arsenic exposure are available in the literature. We therefore studied this aspect in a murine model. METHODS: BALB/c mice were given arsenic-contaminated (3.2 mg/L) or arsenic-free (< 0.01 mg/L, control) drinking water ad libitum. Batches of mice were sacrificed after 2 and 4 months, and blood samples and liver tissue were collected. Liver histology was examined and levels of hepatic reduced glutathione (GSH), malondialdehyde, and enzymes of the antioxidant defense system in the liver tissue were determined. Arsenic content in liver tissues obtained at 4 months was estimated. RESULTS: Two-month exposure to arsenic caused significant elevation of hepatic GSH (11.4 [0.8] micrograms/mg protein) compared to control mice (9.3 [0.4]; p < 0.01). Levels of enzymes related to GSH homeostasis were also elevated. At 4 months, hepatic GSH was significantly reduced (8.4 [0.5] micrograms/mg protein) when compared to control mice (9.3 [0.4]; p < 0.01). Arsenic content in the liver tissue after 4 months of exposure was significantly higher (0.40 [0.05] microgram/g) as compared to control mice (0.04 [0.04]; p < 0.01). CONCLUSION: The results suggest that the antioxidant defense system in the liver of mice is activated after exposure to arsenic for 2 months. However, prolonged exposure to arsenic probably causes overuse failure of this system, which might result in initiation of biochemical injury to the liver.

Esophageal and gastric dysmotility in non ulcer dyspepsia.

BACKGROUND: The pathophysiology of non ulcer dyspepsia is poorly understood. Data on gastrointestinal motility alterations in this condition in the Indian population are scanty. We studied esophageal and gastric motility in patients with non ulcer dyspepsia. METHODS: 58 consecutive patients with non ulcer dyspepsia (according to the Rome criteria) were studied; 10 healthy volunteers were studied as controls. Esophageal transit of solid and liquid boluses (in all patients) and solid-phase gastric emptying (in 20 patients) were studied using scintigraphic techniques. RESULTS: Delayed esophageal transit and delayed gastric emptying were observed in 32 (55%) and 9 (45%) patients, respectively. Delay of both esophageal and gastric transit was found in 5 patients. Mean (SD) esophageal transit for liquid bolus was significantly delayed in patients (9.3 [3.7] s) compared to controls (7.0 [2.0] s; p < 0.01). Mean (SD) gastric emptying time (T50) was significantly delayed in patients (61.6 [13.6] min) compared to controls (50.0 [5.0] min; p < 0.001). Esophageal and gastric delayed transit was found in about two thirds of patients with dysmotility-like dyspepsia, but there were no significant difference in these abnormalities among different subgroups of dyspepsia. CONCLUSION: High prevalence of esophageal and gastric transit delay was found in non ulcer dyspepsia, particularly in the dysmotility subgroup.

Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.

Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes. We have studied skin biopsies from 42 patients of CAT. Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases. Squamous cell carcinoma was present in 2, basisquamous in 1 and basal cell carcinoma in 1 case. Changes of skin lesions after drug DMSA and DMPS therapy compared to placebo were studied. The result was inconclusive. Proliferative activity of skin lesions in CAT were studied by AgNOR stain to assess the biological behaviour of the lesions. AgNOR score showed--normal control 1.08, benign changes (e.g. Hyperkeratosis, parakeratosis, acanthosis, papillomatosis etc.) without dysplasia--1.35, mild to moderate dysplasia--1.735, severe dysplasia--3.0 and carcinoma--3.56. Thus, AgNOR score gives some idea on the biological behaviour of CAT lesions. It is suggested that AgNOR staining should be done regularly along with H&E staining for proper assessment of the cases.

Development of an animal model of hepatic fibrosis by excretory-secretory antigen of Ascaris suum.

OBJECTIVE: The excretory-secretory (ES) antigens of Ascaris suum are known to cause hepatic damage in animals. The present study was aimed at developing an animal model of hepatic fibrosis with these antigens. METHODS: Three doses of ES antigens of A. suum were injected into 24 golden hamsters on days 0, 10 and 20. Batches of 8 animals each were sacrificed at 3 days, 45 days and 90 days after the third injection, after collection of blood. Three groups of 6 control animals each were injected with normal saline and were sacrificed similarly. Liver biochemistry, leukocyte migration inhibition test on cells separated from spleen, and liver histology were carried out. RESULTS: Serum ALT levels in experimental animals were significantly higher than those in control animals at days 3, 45 and 90 after the last antigen dose; AST levels were elevated 45 and 90 days after the last dose of ES antigen. Leukocyte migration inhibition in experimental animals was 58.2 (8.5)%, 51.6 (11.2)% and 50.5 (12.8)% at days 3, 45 and 90 after the last antigen dose. Marked centrivenular degeneration and necrosis were observed in liver tissue in all the experimental animals sacrificed 72 h after the last antigen dose. Condensation of reticulin around the portal zone with extension into the liver lobule was observed in 4 of 8 and 7 of 8 experimental animals sacrificed 45 and 90 days, respectively, after the last dose. Control animals did not have such lesions. CONCLUSION: An animal model of hepatic fibrosis could be produced by repeated injection of ES antigens of A. suum.

Oxidative stress in gastric mucosa in Helicobacter pylori infection.

BACKGROUND: Infection with Helicobacter pylori is believed to be associated with generation of reactive oxygen molecules which leads to oxidative stress in the gastric mucosa; but the relation between oxidative stress and gastrointestinal mucosal damage has not been documented. AIM: To look for evidence of oxidative stress and lipid peroxidation in the gastric mucosa in H. pylori-associated peptic ulcer. METHODS: 34 duodenal ulcer (DU) patients with H. pylori infection, 14 DU patients without H. pylori infection and 10 healthy subjects without H. pylori infection were studied. H. pylori infection was diagnosed by histology and rapid urease test on endoscopic biopsies from the gastric body and antrum. Reduced glutathione (GSH) and malondialdehyde (MDA) content were measured in biopsies taken from the gastric antrum. Statistical analysis was done using Student's t test. RESULTS: Tissue levels of GSH were significantly lower (91.7 [35.4] nmole/100 mg versus 147.3 [41.2] nmole/100 mg; p < 0.001) and MDA higher (163.0 [83.4] nmole/100 mg versus 109.2 [51.3] nmole/100 mg; p < 0.01) in patients with DU associated with H. pylori infection as compared to those without H. pylori infection. GSH levels were significantly lower and MDA levels higher in DU patients with or without H. pylori infection as compared to control subjects. Serum MDA levels in DU patients with H. pylori infection were also significantly higher than in patients without H. pylori infection. CONCLUSION: Depletion of gastric mucosal glutathione in H. pylori-infected DU patients may be due to failure of the antioxidant defense system. Failure of the glutathione-dependent defense system results in accumulation of free radicals which can initiate membrane damage by lipid peroxidation.

Hepatic manifestations in chronic arsenic toxicity.

OBJECTIVE: The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognized. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. We report the nature and degree of liver involvement on the basis of hospital-based and cohort follow-up studies in patients who consumed arsenic-contaminated drinking water for 1 to 15 years. METHODS: 248 patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examinations including liver function tests and HBsAg status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. A cohort follow up of 23 patients who took arsenic-free water for 2-12 years was also carried out. RESULTS: Hepatomegaly was present in 190 of 248 patients (76.6%). Noncirrhotic portal fibrosis (91.3%) was the predominant lesion in liver histology. The maximum arsenic content in liver was 6 mg/Kg (mean 1.46 [0.42], control value 0.16 [0.04]; p < 0.001); it was undetected in 6 of 29 samples studied. Cohort follow-up studies showed elevation of globulin in four cases and development of esophageal varices in one case. CONCLUSION: We report the largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic-contaminated water. Noncirrhotic portal fibrosis is the predominant lesion in this population.

Prevalence of hepatitis B infection in the general population: a rural community based study.

BACKGROUND: Available seroprevalence studies of hepatitis B in Indian population has limitations. A community based door to door epidemiological study was conducted between December 1997 and January 1988 to look for the dynamics of hepatitis B exposure in a single village of West Bengal. METHODS: In all, 960 inhabitants out of 1261 (according to 91 census) in a village of Birbhum district in West Bengal were interviewed and their blood were tested by ELISA for HBV exposure. Odds ratio was calculated to estimate the relative risks for each potential factor facilitating virus transmission. RESULTS: Participation rate in the present study was 76.1%. Over all HBsAg carrier rate was found to be 5.3%. Only 2/51 (3.9%) carriers were HBeAg positive. Injection by glass syringe (odds ratio = 3.01), age < 20 years (odds ratio = 1.41) and male sex (odds ratio = 1.57) were significant risk factor. CONCLUSION: The results of this rural, predominantly poor, agrarian worker based community data reveals a fairly large reservoir of infection (5.3%). It is mainly built-up early in life. Injection practices need to be safer in addition to HBV vaccination to fight this menace.