Factor V Leiden and prothrombin gene G20210A mutations are uncommon in portal vein thrombosis in India.

BACKGROUND: Extra-hepatic portal vein obstruction due to portal vein thrombosis (PVT) is an important cause of portal hypertension in several regions including India. The cause of thrombosis in these patients remains unclear. We studied the frequency of mutations in genes for coagulation factors V and II (prothrombin) in 61 Indian patients with PVT and 49 healthy control subjects. METHODS: The presence of factor V Leiden mutation and of G20210A prothrombin gene mutation was determined using polymerase chain reaction followed by restriction fragment length polymorphism. Chi-squared test was used to compare patients and controls. RESULTS: Of the 61 patients (median age 11 years; 47 male) studied, 49 were children. One of 61 (1.6%) patients with PVT was heterozygous for factor V Leiden mutation and none had the G20210 prothrombin gene mutation. The frequencies of these mutations were not different from those in control subjects (2/49 and 0/46, respectively). CONCLUSION: Factor V Leiden and G20210 prothrombin gene mutations are infrequent in Indian patients with PVT. Thus, these mutations are unlikely to be responsible for PVT in the Indian population.

Low frequency of factor V Leiden and prothrombin G20210A mutations in patients with hepatic venous outflow tract obstruction in northern India: a case-control study.

BACKGROUND: Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are known to be associated with venous thromboembolism. Several studies have shown an association of these mutations with hepatic venous outflow tract obstruction (HVOTO). We studied the prevalence of these mutations among patients with HVOTO in northern India in comparison with healthy population. METHODS: Genomic DNA from patients with HVOTO and healthy controls was analyzed for the presence of FVL and prothrombin gene G20210A mutations, using PCR and restriction-fragment length polymorphism. RESULTS: Fifty-nine patients with HVOTO (age 5-69 years, median 27; 39 male) and 49 unrelated healthy controls from the same geographic region were studied. Of the 59 patients, 19 had a block in the hepatic vein, 7 in inferior vena cava, and 33 had mixed block. Presentation was with acute thrombosis in 9 patients and with long-standing obstruction in 50 patients. Among 49 controls, heterozygous and homozygous FVL mutations were observed in 2 and 0 subjects, respectively, with an allele frequency of 2% (2 of 98). In comparison, among 59 patients with HVOTO, four had heterozygous and none had homozygous FVL mutation, with an allele frequency of 3.4% (p=ns versus controls). The G20210A prothrombin gene mutation was not found in any of the patients or controls. CONCLUSION: FVL and prothrombin G20210A mutations appear to have no role in the pathogenesis of HVOTO in our patients with Budd-Chiari syndrome, consisting largely of those with long-standing obstruction of the inferior vena cava.

Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D.

BACKGROUND: The clinical outcome of chronic hepatitis B may depend on hepatitis B virus (HBV) genotype. Data from India on this aspect are limited and contradictory. We studied the frequency of HBV genotypes and their clinical significance. METHODS: Stored sera from patients with chronic HBV infection were tested for HBV genotype using PCR-RFLP. Clinical data, and biochemical and serological parameters were retrieved from medical records; patients were classified as having chronic hepatitis or cirrhosis. RESULTS: Of 70 patients studied (mean age [SD] 38.4 [17.0] years; 63 men; ALT 140 [177] U/L), 32 had chronic hepatitis and 38 had cirrhosis. HBeAg was positive in 50/67 (75%), and anti-HBe in 12/66 (18%). Genotype A was the commonest (37; 53%), followed by D (32; 46%) and C (1; 1%). Patients with genotype A more often had ALT elevation exceeding 1.5 times normal (30/37 [81%] than those with genotype D (18/31 [58%]; p< 0.05). They also more often had positive HBeAg (32/37; 86%) and negative anti-HBe (33/36; 92%) than those with genotype D (18/29 [62%] and 21/29 [72%], respectively; p< 0.05 each). Of 37 patients with genotype A, 23 (62%) had cirrhosis and 14 (38%) had chronic hepatitis; of 32 patients with genotype D, 15 (47%) had cirrhosis and 17 (53%) had chronic hepatitis (p=ns). In the subgroup aged> 25 years, genotype A patients more often had cirrhosis than those with genotype D (23/28 [82%] vs 13/23 [57%]; p < 0.05). CONCLUSION: HBV genotypes A and D were the commonest in our population. Genotype A was more often associated with ALT elevation, HBeAg positivity, absence of anti-HBe and, among those aged 25 years and above, cirrhosis of liver, than was genotype D.