What makes non-cirrhotic portal hypertension a common disease in India? Analysis for environmental factors

In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.

Prevalence of non-responsiveness to an indigenous recombinant hepatitis B vaccine: A study among South Indian health care workers in a tertiary hospital.

Background and Aim: Health care workers (HCW) are at higher risk of contracting HBV infection. Non-response to HBV vaccine is one of the major impediments to prevent healthcare associated HBV infection (HAHI). We estimated the prevalence of non-responsiveness to initial 3-dose regimen of an indigenous recombinant HBV vaccine (GeneVac-B) among South Indian HCWs and typed the HLA in non-responders. Study Design and Method: Of the 778 subjects screened over 1 year, 454 completed all three doses of the hepatitis B vaccination. Anti-HBs titers were estimated by microparticle enzyme immunoassay AxSYM AUSAB, (Abbott, Germany). HLA typing was done using SSP-PCR assay AllSet+™ Gold SSP (Invitrogen, USA). Results: The overall seroconversion rate (anti-HBs > 10 mIU/mL) was 98.89% wherein 90.8% had titers >1000mIU/mL, 7.6% had titers 100–1000mIU/mL, 0.43% had titers < 100 mIU/mL and 1.1% were non-responsive (<10 mIU/mL) to the initial 3-dose regimen. Antibody titers <1000 mIU/mL were signifi cantly associated with the highest quartile of body mass index (BMI) (P < 0.001). We found no signifi cant difference in seroprotection rate between gender (P = 0.088). There was no difference in seroprotection rates among various ethnic groups (P = 0.62). Subjects who were non-responsive in our study had at least one HLA allele earlier known to be associated with non-responsiveness to the vaccine. Conclusion: Our fi ndings suggest that non-response to HBV vaccine is not a major impediment to prevent HAHI. Robust seroprotection rates can be achieved using this indigenous HBV vaccine. However, gender and BMI might infl uence the level of anti-HBs titers. We recommend the use of this cost effective HBV vaccine as well as postvaccination anti-HBs testing to prevent HAHI among HCWs.

A study of aetiology of portal hypertension in adults (including the elderly) at a tertiary centre in southern India.

Background & objectives: There are only a few studies on aetiology of portal hypertension among adults presenting to tertiary care centres in India; hence we conducted this study to assess the aetiological reasons for portal hypertension in adult patients attending a tertiary care centre in southern India. Methods: Causes of portal hypertension were studied in consecutive new adult patients with portal hypertension attending department of Hepatatology at a tertiary care centre in south India during July 2009 to July 2010. Results: A total of 583 adult patients (>18 yr old) were enrolled in the study. After non-invasive testing, commonest causes of portal hypertension were cryptogenic chronic liver disease (35%), chronic liver disease due to alcohol (29%), hepatitis B (17%) or hepatitis C (9%). Of the 203 patients with cryptogenic chronic liver disease, 39 had liver biopsy - amongst the latter, idiopathic non cirrhotic intrahepatic portal hypertension (NCIPH) was seen in 16 patients (41%), while five patients had cirrhosis due to non alcoholic fatty liver disease. Fifty six (10%) adult patients with portal hypertension had vascular liver disorders. Predominant causes of portal hypertension in elderly (>60 yrs; n=83) were cryptogenic chronic liver disease (54%) and alcohol related chronic liver disease (16%). Interpretation & conclusions: Cryptogenic chronic liver disease was the commonest cause of portal hypertension in adults, followed by alcohol or hepatitis B related chronic liver disease. Of patients with cryptogenic chronic liver disease who had liver biopsy, NCIPH was the commonest cause identified. Vascular liver disorders caused portal hypertension in 10 per cent of adult patients. Cryptogenic chronic liver disease was also the commonest cause in elderly patients.

Infection with hepatitis C virus genotype 3 - Experience of a tertiary health care centre in south India.

To analyse the response rate and the predictive values of virological, biochemical and histological factors on HCV antiviral therapy in HCV genotype 3 infected patients, we retrospectively studied 21 HCV genotype 3 infected patients, who underwent HCV antiviral therapy. Low (57%) sustained viral response (SVR) rate and significant association of SVR with normalization of alanine transaminase (ALT) levels were observed in our study. Absence of early viral response (EVR) showed high (80%) predictive value on SVR. Absence of EVR and normalisation of the ALT levels can predict the outcome of HCV antiviral therapy.

Branding to treat jaundice in India.

Jaundice is regarded as a mysterious disease rather than a symptom of disease in several parts of India. We describe 8 cases that underwent branding to treat jaundice and subsequently presented to our centre. The causes for jaundice in these patients included a variety of benign and malignant disorders. Our report suggests that despite being literate, strong cultural beliefs lead people to seek potentially harmful procedures like branding to treat jaundice in parts of India.

Idiopathic non-cirrhotic intrahepatic portal hypertension: common cause of cryptogenic intrahepatic portal hypertension in a Southern Indian tertiary hospital.

Background and aim Patients with intrahepatic portal hypertension and negative etiological work-up for liver disease are often labeled as having cryptogenic cirrhosis. The aim of this study was to evaluate causes of liver disease in patients with unexplained intrahepatic portal hypertension. Methods We retrospectively analyzed cause of liver disease in all patients with cryptogenic intrahepatic portal hypertension who underwent liver biopsies between June 2005 to June 2007 in our center. Results Five hundred and seventeen patients underwent liver biopsies of whom 227 had portal hypertension. Of these, the cause of liver disease could not be detected prior to liver biopsy in 62 patients. Causes of liver disease identified after liver biopsy in these 62 patients were: idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) (30 patients, 48 ), cirrhosis (14), fatty liver disease (7) and other causes (11). Initial presentations in idiopathic NCIPH patients were splenomegaly and anemia (18 patients), variceal bleed (9) and ascites (3). Median age (range) of patients at first presentation was 32 (15-57) years, and 19 were male. Majority (90 ) were in Child’s class A. Hepatic vein pressure gradient was <5 mmHg in 2 of 7 NCIPH patients tested. Conclusions We identified 30 patients with idiopathic NCIPH at our center over the 2 year study period. The clinical presentation and investigations of NCIPH closely mimic cryptogenic cirrhosis. Idiopathic NCIPH should be considered as a differential diagnosis of cryptogenic cirrhosis in India.

Changing profile of Budd Chiari syndrome in India.

There is increasing evidence that Budd Chiari syndrome occurs when acquired predisposing factor(s) affect a susceptible individual with one or more underlying thrombophilic conditions. Geographical variations in disease pattern of Budd Chiari syndrome exist, which may reflect differing predisposing factors. We review a change in disease profile of Budd Chiari syndrome in India over the past three decades. While earlier studies from India reported isolated inferior vena cava (IVC) obstruction as the commonest disease type, this is a minority in more recent reports where a combination of IVC and hepatic vein obstruction is the commonest type. Longer duration of illness has been shown to be associated with IVC obstruction and the recent change in disease profile in India may reflect earlier diagnosis of Budd Chiari syndrome. Poverty, malnutrition, recurrent bacterial infections and filariasis have been previously suggested as predisposing factors for IVC obstruction. Improvement in hygiene and sanitation may partly explain the recent change in disease profile of Budd Chiari syndrome in India.

ATP7B mutations in families in a predominantly Southern Indian cohort of Wilson's disease patients.

OBJECTIVE: To analyze ATP7B mutations in Wilson's disease (WD) patients from the Indian subcontinent and to correlate these with WD phenotype. METHODS: We studied 27 WD patients from 25 unrelated families. Twenty-two families were from three southern Indian states - Tamil Nadu andhra Pradesh and Kerala. We applied conformation- sensitive gel electrophoresis (CSGE) to screen for the mutations in patients and their families. PCR products exhibiting aberrant patterns in CSGE were subjected to direct DNA sequencing. As siblings affected by WD within a family share identical ATP7B genotype, we compared WD phenotype among affected siblings within families. RESULTS: ATP7B mutations were detected in 22 of the 25 probands -13 were homozygotes and 9 were compound heterozygotes. Eleven novel mutations were detected. Only two common mutations were found: G3182A in 4 (16%) and C813A in 3 (12%) probands. 'Hot spots' for ATP7B mutations were exons 18 and 13. Lack of common dominant mutations prevented correlation of individual ATP7B mutations with WD phenotype. Symptomatic WD in a live sibling was not found in any family. In 8 families, a sibling died of presumed WD - in 6 of these, WD phenotype was identical to that in the proband. CONCLUSIONS: We describe the spectrum of ATP7B mutations including 11 novel mutations in Indian WD patients and document lack of a single dominant mutation. Identical WD phenotype among siblings in only 6 of 8 families with >1 child affected by WD suggests that factors other than ATP7B mutations influence WD phenotype.

Liver histology and immunohistochemical findings in asymptomatic Indians with incidental detection of hepatitis B virus infection.

BACKGROUND AND OBJECTIVES: The relationship between hepatocyte expression of hepatitis B virus (HBV) antigens, liver histology and viral replication in asymptomatic subjects with incidental detection of hepatitis B surface antigen (HBsAg) remains unclear. We evaluated the histological activity index (HAI) and hepatocyte expression of viral antigens with replicative status in asymptomatic chronic HBV infection. METHODS: Asymptomatic subjects with incidental detection of HBsAg and ALT levels less than twice the upper limit of normal were grouped as follows: Group A - negative for HBeAg and HBV DNA (no HBV replication); B - HBeAg negative, HBV DNA positive (low HBV replication or pre-core mutant); C - positive HBeAg and HBV DNA (high viral replication). Liver biopsies were assessed for HAI (Ishak's scoring system). These were also subjected to immunohistochemistry for expression of HBsAg and hepatitis B core antigen (HBcAg); distribution, staining pattern and quantitative measurement of antigen expression were assessed. RESULTS: Median HAI was similar in the three groups (1.0, 2.0 and 2.0 in groups A, B and C, respectively). All subjects in Group C showed discrete cytoplasmic expression of HBsAg, whereas the other two groups showed heterogeneity in distribution and pattern of HBsAg staining. Quantitative measurement of cytoplasmic HBsAg revealed similar results in the three groups. Core antigen (nuclear) was detected in 4 of 5 subjects in Group C and none of those in Groups A and B. Ground-glass hepatocytes were seen in 20 and orcein-positive cells in 26 cases. HBsAg was detected by immunohistochemistry in 37 biopsies. CONCLUSIONS: Among asymptomatic subjects with chronic HBV infection, those with high rate of viral replication had discrete cytoplasmic HBsAg expression and nuclear expression of core antigen; these findings were uncommon in subjects with low or no viral replication.

Tyrosinemia type I: a clinico-laboratory case report.

Progressive hepatocellular dysfunction in a neonate, resulting in elevated serum alpha-fetoprotein together with raised blood levels of tyrosine and methionine, a generalized amino aciduria and the absence of urinary delta-aminolevulinic acid and succinylacetone, suggests a diagnosis of tyrosinemia type Ib. Classical tyrosinemia type I arises from a deficiency of fumarylacetoacetate hydrolase while the variant tyrosinemia type Ib results from a deficiency of maleylacetoacetate isomerase.

Transcatheter hepatic artery embolization for spontaneous rupture of amyloid liver.

Spontaneous rupture of amyloid liver is a fatal complication. A 48-year-old man with systemic amyloidosis secondary to multiple myeloma presented with acute hemoperitoneum. Emergency angiogram showed extravasation of contrast from the liver into the sub-hepatic space, which was successfully stopped by embolization of the right hepatic artery.

Neurologic deterioration in a child with Wilson's disease on penicillamine therapy.

Penicillamine is the standard therapy for Wilson's disease in children. We report an 8-year-old-girl with liver disease due to Wilson's disease who developed extrapyramidal symptoms following administration of penicillamine. Symptoms resolved within 20 hours of stopping the drug but recurred within 24 hours when gradually increasing small doses were recommenced.

Intussusception in southern Indian children: lack of association with diarrheal disease and oral polio vaccine immunization.

BACKGROUND: Intussusception is the most common cause of intestinal obstruction in young children and has been reported as a complication of a recently withdrawn tetravalent reassortant rotavirus vaccine. METHODS: We studied the history, clinical presentation, management and outcome of intussusception presenting to a tertiary care hospital in southern India over a 10-year period, in order to assess potential association with diarrheal disease and immunization. RESULTS: Data from 137 index cases and 280 control subjects indicated that the risk of diarrheal disease or oral polio vaccine administration in the month prior to presentation was similar in the index cases and controls. Mean time to presentation to hospital after developing symptoms was 1.8 days, and 77.3% of patients required surgery, with 47.4% undergoing intestinal resection. Mortality was 0.006%. CONCLUSIONS: No association could be demonstrated between gastroenteritis or oral poliovirus vaccine immunization and intussusception in southern Indian children. These children presented later and required operative intervention more frequently than has been reported in other studies, but had a good outcome with low mortality.