Recombinant macrophage targeted enzyme replacement therapy for Gaucher disease in India.

OBJECTIVE: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease. DESIGN: Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase. SETTING: Five centers from India with experience in treating lysosomal storage disorders. PATIENTS: The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombo-cytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days. MAIN OUTCOME MEASURES: Hemoglobin, platelet counts, liver and spleen volumes and growth parameters. RESULTS: 22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 10(9)/L (-98.5 x 109 to 145.5 x10(9))/L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static. CONCLUSIONS: This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.

Transjugular intrahepatic portosystemic shunt (TIPSS) for Budd Chiari syndrome.

We report a four year old boy who presented with liver failure secondary to anti-thrombin III deficiency related Budd Chiari syndrome. He was treated with TIPSS (transjugular intrahepatic porto systemic shunt) which reversed the encephalopathy, normalised the liver function and improved growth, pre-empting the need for a liver transplantation. This is the first reported case of TIPSS in a child with a fulminant presentation of Budd-Chiari Syndrome.

Dapsone hypersensitivity syndrome with coexisting acute hepatitis E.

A 14-year-old girl presented with fever, generalized lymphadenopathy, skin rash and hepatitis after starting dapsone. All abnormalities reversed with institution of prednisolone therapy after discontinuation of dapsone. The hepatic involvement was of hepatocellular type; it was associated with IgM anti-HEV antibodies, suggesting coexisting acute hepatitis E. We believe a causal link between the hepatotrophic viruses and dapsone hypersensitivity syndrome could exist.

Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease.

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2-24.8) mg/l. compared with 6.6 mg/l (11.2-24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.

Portal hemodynamics in chronic liver disease.

Portal hypertension is a result of interplay of numerous static and dynamic forces. Portal hemodynamic characterization involves pressure and flow studies which in turn estimate portal pressure. Hepatic venous pressure gradient is the gold standard for determining portal pressure. Portal hemodynamic measurement has helped to understand the pathogenesis and prognosis of chronic liver disease and to define clinically important hepatic venous pressure gradients. Management strategies for ascites and prevention of variceal hemorrhage have been influenced by hemodynamic studies in animals and humans. The hemodynamics in non-cirrhotic portal fibrosis is ambiguous. The role of portal hemodynamic studies outside clinical trials needs further study.

Hepatic sickling crisis mimicking recurrent cholangitis.

A 22-year-old man with homozygous sickle cell disease presented with recurrent fever, right upper quadrant pain and jaundice. Liver biopsy confirmed the diagnosis of hepatic sickling crisis; the symptoms responded to hydroxyurea therapy. Hepatic vasocclusive crisis can diagnosed on liver biopsy, and need not be a diagnosis of exclusion.

Autoimmune sclerosing cholangitis: an overlap syndrome in a child.

We report an overlap syndrome of autoimmune chronic liver disease and primary sclerosing cholangitis in a young girl. This could be the first such report from India.

Eosinophils in acute cellular rejection in liver allografts.

Eosinophils have a role in various allergic and inflammatory disease processes and participate in the process of acute rejection in solid organ allografts. Initial studies described the diagnostic value of eosinophils in kidney allograft rejection. Graft eosinophilia is a sensitive and specific marker of acute rejection in liver allografts and has been incorporated as one of the diagnostic criteria of acute rejection by the Royal Free Hospital scoring system. Blood eosinophilia also has been investigated and is a useful diagnostic marker of acute rejection in liver and kidney allografts, although studies differ in defining the day of onset of eosinophilia in relation to rejection. Eosinophils probably act through the chemokines interleukin-5 and RANTES (regulated on activation, normal T cells expressed and secreted) in the pathogenesis of acute rejection. Basic cytotoxic proteins, such as eosinophil cationic protein and major basic protein, are released by the eosinophils, and their effector role in acute rejection has been studied through the use of specific monoclonal antibodies. Successful treatment of acute rejection with corticosteroids has been associated with a decrease in graft and blood eosinophil counts. Eosinophils also act as prognostic markers of acute rejection, as shown by studies reporting that patients with elevated eosinophil counts and steroid-resistant rejection showed a worse prognosis. Further research into the effector mechanisms of eosinophils in acute rejection needs to be performed. The ability of eosinophils to distinguish those diseases with different responses to standard immunosuppression and other diseases in the context of acute rejection also needs to be studied.

"Salvage" transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.

BACKGROUND & AIMS: The optimal emergency treatment for gastric fundal variceal bleeding is still unclear. In this study, the efficacy of transjugular intrahepatic portosystemic stent/shunt (TIPS) in patients with uncontrolled gastric fundal vs. esophageal variceal bleeding was compared. METHODS: One hundred twelve consecutive patients with uncontrolled variceal bleeding required emergency TIPS, 84 with esophageal varices (EV group) unresponsive to endoscopic and vasoconstrictor therapy and 28 with gastric fundal varices (GV group) unresponsive to vasoconstrictor therapy. Clinical and biochemical data were retrieved, and the two groups were compared. RESULTS: Variceal bleeding was controlled in all patients after TIPS except for 1 in each group. There were no significant differences between the two groups in terms of markers of disease severity, severity of bleeding, or portal hemodynamics. During a median follow-up period of 7 months, 20 in the EV group (24%) and 8 in the GV group (29%) developed clinical rebleeding. Most early rebleeding (within 7 days after TIPS) was related to esophageal ulceration secondary to previous sclerotherapy. Rates of mortality were similar in both groups. CONCLUSIONS: These results suggest that emergency TIPS is equally effective in the immediate short-term control of gastric fundal variceal bleeding compared with esophageal variceal bleeding.

Alpha-glutathione-S-transferase in acute rejection of liver transplant recipients.

BACKGROUND: Alpha-glutathione-S-transferase (alphaGST) has been suggested as a sensitive marker of acute cellular rejection in liver transplantation. This study evaluated the usefulness of alphaGST as a marker of acute rejection in comparison with standard liver function tests. METHODS: Daily measurements of liver function tests and alphaGST (enzyme immunometric assay, Biotrin) were prospectively recorded in 23 consecutive liver transplant recipients up to the time of discharge. Liver biopsies were performed as protocol biopsies or after clinical or biochemical deterioration in liver function, 38 of 56 showed acute rejection. RESULTS: AlphaGST peaked on the second day (median, 125 microg/L; interquartile [IQ] range, 75-321 microg/L) and preceded the alanine transaminase (ALT) peak by 1 day. AlphaGST levels then steadily declined, reaching baseline by day 6, plateauing until day 8. After the initial peak, alphaGST still correlated well with the ALT (median correlation coefficient, 0.6; IQ range, 0.45-0.77) and with bilirubin concentration (median correlation coefficient, 0.47; IQ range, 0.14-0.6). There was no significant difference in alphaGST levels between those with rejection compared with other causes of hepatic dysfunction. The sensitivity and specificity of alphaGST for diagnosing acute rejection was 63.1% and 38.8%, respectively, compared with 97.4% and 16.7% for ALT. In 14 of the 16 patients treated for moderate or severe rejection, the improvement in the histological score of rejection was not associated with a consistent change in the alphaGST. CONCLUSIONS: AlphaGST is not more useful than ALT in diagnosing rejection or determining response to treatment, but is a sensitive marker of liver injury.

Epidemiology of digestive tract cancers in India. II. Stomach, and gastrointestinal lymphomas.

The incidence of stomach cancer and GI lymphomas is low in most parts of India. There is paucity of analytical epidemiologic data on these from India. While the time trends for the incidence of gastric cancer are encouraging, most cancers are diagnosed in an advanced stage when long-term cure is only a remote possibility. Multi-center epidemiologic studies should be undertaken to solve some of the enigmas and observations peculiar to India.