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.

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.

Quantitation of hepatitis B virus DNA in plasma using a sensitive cost-effective "in-house" real-time PCR assay.

BACKGROUND: Sensitive nucleic acid testing for the detection and accurate quantitation of hepatitis B virus (HBV) is necessary to reduce transmission through blood and blood products and for monitoring patients on antiviral therapy. The aim of this study is to standardize an "in-house" real-time HBV polymerase chain reaction (PCR) for accurate quantitation and screening of HBV. MATERIALS AND METHODS: The "in-house" real-time assay was compared with a commercial assay using 30 chronically infected individuals and 70 blood donors who are negative for hepatitis B surface antigen, hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody. Further, 30 HBV-genotyped samples were tested to evaluate the "in-house" assay's capacity to detect genotypes prevalent among individuals attending this tertiary care hospital. RESULTS: The lower limit of detection of this "in-house" HBV real-time PCR was assessed against the WHO international standard and found to be 50 IU/mL. The interassay and intra-assay coefficient of variation (CV) of this "in-house" assay ranged from 1.4% to 9.4% and 0.0% to 2.3%, respectively. Virus loads as estimated with this "in-house" HBV real-time assay correlated well with the commercial artus HBV RG PCR assay ( r = 0.95, P < 0.0001). CONCLUSION: This assay can be used for the detection and accurate quantitation of HBV viral loads in plasma samples. This assay can be employed for the screening of blood donations and can potentially be adapted to a multiplex format for simultaneous detection of HBV, HIV and HCV to reduce the cost of testing in blood banks.

Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population.

BACKGROUND/OBJECTIVES: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. METHODS: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. RESULTS: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). CONCLUSIONS: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.

Direct intrahepatic cavo-portal shunts in Budd-Chiari syndrome: Role of simultaneous fluoroscopy and trans-abdominal ultrasonography.

BACKGROUND: Transjugular intrahepatic porto-systemic shunt (TIPS) for Budd-Chiari syndrome (BCS) can be inserted from inferior vena cava or hepatic vein to portal vein. The former is performed when hepatic veins are not suitable and is technically more challenging. METHODS: In this retrospective study, 7 patients with chronic BCS needed cavo-portal shunt as hepatic veins were neither amenable to plasty nor provided access for TIPS placement. Simultaneous fluoroscopic and trans-abdominal ultrasound guidance was used at the time of portal vein puncture. RESULTS: Technical success and clinical improvement were obtained in all patients. Median 3 (range 1-4) attempts were needed to puncture the portal vein. There were no significant complications. Uncovered stents were used in six patients and stent occlusion was common, but could be managed by re-intervention. CONCLUSION: Cavo-portal shunt is an effective technique for patients with BCS uncontrolled by medical therapy. Additional trans-abdominal ultrasound in oblique parasagittal plane keeps the procedure safe.

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.

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.

Assessing the severity of hepatic encephalopathy.

The diagnosis of hepatic encephalopathy (HE) is based mostly on clinical criteria. It is important to assess the severity of HE quantitatively for both clinical practice and research; however, this remains a difficult and challenging problem. Modalities like psychometric tests, electroencephalography, evoked potentials, and several innovative biochemical indices have shown promise in this regard. No single parameter or index has yet been shown to be infallible in assessing the severity of HE.

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.

Acute fatty liver of pregnancy: a report of two cases.

Acute fatty liver of pregnancy is an uncommon, potentially fatal disorder. Between 1998 and 2000, two patients with acute fatty liver of pregnancy presented at the Christian Medical College Hospital, Vellore. Both patients were in the thirty-sixth week of pregnancy. jaundice and encephalopathy were the predominant symptoms. Both the mothers died after they delivered a stillborn Infant each. The maternal deaths were due to multiorgan failure and/or postpartum haemorrhage and sepsis. The route of delivery was vaginal in both the patients. Extrahepatic and metabolic complications in both cases Included renal failure, sepsis, hypoglycaemia, disseminated intravascular coagulation and gastrointestinal bleeding. Liver biopsy done in both patients was consistent with the diagnosis of acute fatty liver of pregnancy. To the best of our knowledge, this is the first report from India on acute fatty liver of pregnancy.