Bio

Publications


2009

Mugambi-Nturibi, E, Otieno CF, kwasa TO, Oyoo GO, Acharya K.  2009.  Stratification of persons with diabetes into risk categories for foot ulceration. Abstract

Patients with diabetes mellitus are at a higher risk of lower extremity complications as compared to their non-diabetic counterparts. OBJECTIVE: To study risk factors for diabetic foot ulcer disease and stratify patients with diabetes into risk categories for foot ulceration. DESIGN: Cross-sectional descriptive study over five months period. SETTING: Diabetic outpatient clinic, at the Kenyatta National Hospital. SUBJECTS: Two hundred and eighteen ambulatory subjects with diabetes mellitus without active foot lesions. RESULTS: The prevalence of previous foot ulceration was 16% while that of previous amputation was 8%. Neuropathy was present in 42% of the study subjects and was significantly associated with age, male gender, duration of diabetes, random blood sugar, systolic blood pressure and the presence of foot deformity. Peripheral arterial disease was present in 12% and showed significant association with male gender. Foot deformities were observed in 46% of study subjects and were significantly associated with age, male gender, and presence of neuropathy. Subsequently 57% were categorised into IWGDF group 0--no neuropathy, 10% were placed in group 1--neuropathy alone, 16% were put in group 2--neuropathy plus either peripheral arterial disease or foot deformity and 17% were placed in risk group 3--previous foot ulceration/amputation. CONCLUSION: More than one third (33%) of diabetic patients were found to be at high risk for future foot ulceration (IWGDF groups 2 and 3). Published evidence exists that shows improved outcomes with interventions targeting individual patients with diabetes at high-risk of foot ulceration. Long term prospective studies to determine outcomes for the different risk categories should be carried out locally.

2008

KIRTDA, DRACHARYAS.  2008.  Madan K, Chalamalsetty SB, Srivastava S, Gupta SD, Mirdha BR, Makharia GK, Samataray JC, Acharya SK.Tropical mayhem: a chronic viral disease with superadded parasitic infection.J Med Microbiol. 2008 Feb;57(Pt 2):232-5. J Med Microbiol. 2008 Feb;57(Pt 2):232-5. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Coexistence of two illnesses in the same patient may result in atypical manifestations of either or both diseases. A case of hepatitis B virus-related cirrhosis in a patient who presented with a pharyngeal mucosal mass lesion as a manifestation of superadded Leishmania infection is presented here. The clue to the diagnosis was the origin of the patient from an area highly endemic for leishmaniasis and the presence of unexplained polyclonal hypergammaglobulinaemia. The patient responded very well to therapy with amphotericin B with complete disappearance of the mucosal lesion.
KIRTDA, DRACHARYAS.  2008.  Bhatia V, Singhal A, Panda SK, Acharya SK.A 20-year single-center experience with acute liver failure during pregnancy: Is the prognosis really worse?Hepatology. 2008 Jul 9;48(5):1577-1585. [Epub ahead of print] Hepatology. 2008 Jul 9;48(5):1577-1585. [Epub ahead of print]. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Pregnant patients with acute liver failure (ALF) are believed to have a worse outcome than nonpregnant women and men with ALF. However objective data supporting this supposition are scant. Therefore, the current study compared the outcome, complications, and causes of ALF among pregnant women and girls with age-matched nonpregnant women and girls and men and boys with ALF. One thousand fifteen consecutive ALF patients in the reproductive age group, admitted at the All India Institute of Medical Sciences, New Delhi, from January 1986 to December 2006, were included in the study. A total of 249 (38.5%) women were pregnant. They were compared with 341 nonpregnant women and girls and 425 men and boys, aged 15 to 45 years. The mortality rate of pregnant women and girls (53.8%) was similar to age-matched nonpregnant women and girls (57.2%), and men and boys (57.9%); P = 0.572.The clinical and biochemical features, disease severity, and complications were also similar in the three groups. A significantly higher proportion of ALF was attributable to hepatitis E virus (HEV) among women and girls who were pregnant (59.4%), as compared with both nonpregnant women and girls (30.4%), and men and boys (23.1%); P < 0.001. However, the outcome of HEV-related ALF was independent of the sex and pregnancy status of the patients (P = 0.103). Mortality in HEV-ALF and non-HEV-ALF patients in pregnant women and girls was 51% (74/145) and 54.7% (52/95)(P > 0.1), respectively. The outcome of pregnant ALF patients was also unrelated to the trimester of pregnancy. The mortality of non-HEV-related ALF among the pregnant women and girls (54.7%), age-matched nonpregnant women and girls (61.7%), and men and boys (62.8%) were also similar (P > 0.1). Conclusion: The mortality of pregnant patients with ALF is similar to that of nonpregnant women and girls and men and boys and is independent of the cause or trimester. Pregnancy per se should not be regarded as a poor prognostic factor for a patient with ALF. (HEPATOLOGY 2008.).
KIRTDA, DRACHARYAS.  2008.  Bhardwaj P, Garg PK, Maulik SK, Saraya A, Tandon RK, Acharya SK.A Randomized Controlled Trial of Antioxidant Supplementation for Pain Relief in Patients with Chronic Pancreatitis.Gastroenterology. 2008 Sep 25. [Epub ahead of print]. Gastroenterology. 2008 Sep 25. [Epub ahead of print]. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
{ BACKGROUND & AIMS: Oxidative stress has been implicated in the pathophysiology of chronic pancreatitis (CP). We evaluated the effects of antioxidant supplementation on pain relief, oxidative stress and antioxidant status in patients with CP. METHODS: In a placebo-controlled double blind trial, consecutive patients with CP were randomized to groups that were given placebo or antioxidants for 6 months. The primary outcome measure was pain relief, and secondary outcome measures were analgesic requirements, hospitalization, and markers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant status (ferric-reducing ability of plasma [FRAP]). RESULTS: Patients (age 30.5 +/- 10.5 years, 86 male, 35 alcoholic and 92 with idiopathic CP) were assigned to the placebo (n = 56) or antioxidant groups (n = 71). After 6 months, the reduction in the number of painful days per month was significantly higher in the antioxidant group compared with the placebo group (7.4 +/- 6.8 vs 3.2 +/- 4, respectively; P < .001; 95% CI, 2.07, 6.23). The reduction in the number of analgesic tablets per month was also higher in the antioxidant group (10.5 +/- 11.8 vs 4.4 +/- 5.8 respectively; P = .001; 95% CI, 2.65, 9.65). Furthermore, 32% and 13% of patients became pain free in the antioxidant and placebo groups, respectively (P = .009). The reduction in the level of TBARS and increase in FRAP were significantly higher in the antioxidant group compared with the placebo group (TBARS: placebo 1.2 +/- 2.7 vs antioxidant 3.5 +/- 3.4 nmol/mL; P = .001; 95% CI 0.96, 3.55; FRAP: placebo -5.6 +/- 154.9 vs antioxidant 97.8 +/- 134.9 muMFe(+2) liberated
KIRTDA, DRACHARYAS.  2008.  Madan K, Batra Y, Jha JK, Kumar S, Kalra N, Paul SB, Singh R, Duttagupta S, Panda SK, Acharya SK.Clinical relevance of HBV DNA load in patients with chronic hepatitis B infection.Trop Gastroenterol. 2008 Apr-Jun;29(2):84-90.. Trop Gastroenterol. 2008 Apr-Jun;29(2):84-90.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Hepatitis B virus (HBV) DNA detection and quantification are now playing an increasing role in the assessment of disease activity and response to therapy. However, viraemia levels which define various stages of HBV infection have not yet been established. AIM: To define viraemia levels which describe various stages of chronic hepatitis B virus infection. METHODS: In a retrospective study, stored sera samples of chronic hepatitis B virus (CHB) infected patients registered at AIIMS liver clinic, from January 1996 to June 2005 were subjected to competitive, quantitative PCR analysis. RESULTS: The median HBV DNA load was lowest among carriers and highest among patients with chronic hepatitis B [0 (0-8) vs. 7 (0-12) log10 copies/ml, respectively; p<0.05]. As compared to chronic hepatitis patients the DNA load was also lower among cirrhotics [7 (0-12) vs. 4.5 (0-8) log10 copies/ml, respectively; p<0.05] and hepatocellular cancer patients [ 7(0-12) vs. 0 (0-8) log10 copies/ml, respectively; p<0.05]. Patients with carriers had a DNA load which was significantly lower than e antigen negative CHB [0 (0-8) vs. 6 (0-10) log10 copies/ml; p<0.05] or e antigen positive CHB [0 (0-8) vs 8 (0-12) log10 copies/ml; p<0.05]. A threshold of 3.5 log10 copies/ml had sensitivity and specificity of 83% and 58% respectively in differentiating carriers from e antigen negative CHB. There was a strong positive correlation of HBV DNA load with inflammatory grade (R=0.334; p=0.0001), fibrosis stage (R=0.276; p=0.001) and ALT levels (R=0.378; p=0.0001). 82% (9/11) of those who lost e antigen had a decline in HBV DNA levels to <5 log10 copies/ml, whereas only 12.5% (1/8) of those who did not lose e antigen had a decline in DNA load below this level. CONCLUSIONS: HBV DNA viraemia levels correlate positively with the inflammatory grade, fibrosis stage and ALT levels. Most patients who loose e antigen have a decline in DNA load to below 5 log10 copies/ml. Further prospective studies employing repeated measurements are required to define a threshold to differentiate between HBV carriers and e antigen negative CHB.

2007

KIRTDA, DRACHARYAS.  2007.  Sengupta S, Rehman S, Durgapal H, Acharya SK, Panda SK.Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection.J Med Virol. 2007 Mar;79(3):220-8.. J Med Virol. 2007 Mar;79(3):220-8.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
The production, secretion, and localization of surface proteins of hepatitis B virus (HBV) and the ratio of large to small surface protein S was studied in HepG2 cells transfected with the wild-type and mutant pre-S1 and pre-S2/S promoters of HBV molecular clones 313.1 (GenBank accession no. AY161147) and 761.1 (GenBank accession no. AY161159) from two patients with occult HBV infection. Fusion constructs were made by in frame fusion of the wild-type surface gene to the mutant pre-S1 and pre-S2/S promoters and wild-type promoter so that the structural part of the small surface protein remains identical. HepG2 cells transfected transiently were used for analysis. HBV surface proteins production and secretion was determined by enzyme linked immuno assay (ELISA) and localization by immunofluorescence. Immunoprecipitation of the large, middle, and small surface protein was carried out in transient transfected and metabolically labeled cells to determine the ratio of the large to small surface protein. The results indicate that HepG2 cells transfected with mutant HBV promoters had reduced HBV surface proteins secretion compared to wild-type HBV. HepG2 cells transfected with mutant HBV pre-S1 and pre-S2/S promoters showed cytoplasmic aggregation of HBV surface proteins compared to wild-type HBV promoters, which showed diffuse cytoplasmic localization. In all cases, the HBV surface proteins localized to the endoplasmic reticulum. The ratio between the large and small surface protein was 1.89 and 0.56 with mutant HBV 313.1 and 761.1 pre-S1 and pre-S2/S promoters, respectively, compared to 0.17 in wild-type. Thus, the aggregation of surface proteins, altered ratio and secretion of surface proteins were possibly the causes of occult hepatitis B infection.
KIRTDA, DRACHARYAS.  2007.  Javvaji S, Kumar A, Madan K, Garg PK, Acharya SK.Management of gastric variceal bleeding.Trop Gastroenterol. 2007 Apr-Jun;28(2):51-7.. Trop Gastroenterol. 2007 Apr-Jun;28(2):51-7.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract

OBJECTIVE: This study was undertaken to assess the value of clinical symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha-fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma (HCC) among patients with cirrhosis. MATERIALS AND METHODS: In this cross-sectional study, Child's A/B cirrhosis patients were subjected to clinical evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of clinical symptoms and of AFP at different cut-off levels were determined. Detection rate of HCC and agreement between US and TPCT was estimated. RESULTS: A high proportion of enrolled subjects had HCC at first presentation (40.7%). Significantly higher prevalence of abdominal pain, weight loss, and anorexia was seen in patients with cirrhosis with HCC compared to those without HCC. Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively (positive and negative predictive values of 65 and 85%, respectively). A 100% agreement between TPCT and US was observed for diagnosing HCC cases. However, TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls within the conventional limits of normalcy. CONCLUSION: The study highlights the importance of symptomatology of weight loss, abdominal pain or anorexia as markers for HCC in patients with cirrhosis. AFP was not found to be a useful screening test. TPCT should be undertaken in all cirrhotics presenting to the hospital for the first time. Copyright 2007 S. Karger AG, Basel.

KIRTDA, DRACHARYAS.  2007.  Paul SB, Gulati MS, Sreenivas V, Madan K, Gupta AK, Mukhopadhyay S, Acharya SK.Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein.Oncology. 2007;72 Suppl 1:117-23. Epub 2007 Dec. Oncology. 2007;72 Suppl 1:117-23. Epub 2007 Dec 13.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract

OBJECTIVE: This study was undertaken to assess the value of clinical symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha-fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma (HCC) among patients with cirrhosis. MATERIALS AND METHODS: In this cross-sectional study, Child's A/B cirrhosis patients were subjected to clinical evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of clinical symptoms and of AFP at different cut-off levels were determined. Detection rate of HCC and agreement between US and TPCT was estimated. RESULTS: A high proportion of enrolled subjects had HCC at first presentation (40.7%). Significantly higher prevalence of abdominal pain, weight loss, and anorexia was seen in patients with cirrhosis with HCC compared to those without HCC. Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively (positive and negative predictive values of 65 and 85%, respectively). A 100% agreement between TPCT and US was observed for diagnosing HCC cases. However, TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls within the conventional limits of normalcy. CONCLUSION: The study highlights the importance of symptomatology of weight loss, abdominal pain or anorexia as markers for HCC in patients with cirrhosis. AFP was not found to be a useful screening test. TPCT should be undertaken in all cirrhotics presenting to the hospital for the first time. Copyright 2007 S. Karger AG, Basel.

KIRTDA, DRACHARYAS.  2007.  Paul SB, Sreenivas V, Gulati MS, Madan K, Gupta AK, Mukhopadhyay S, Panda SK, Acharya SK.Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India.Indian J Gastroentero. Indian J Gastroenterol. 2007 Nov-Dec;26(6):274-8.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract

BACKGROUND/AIM: Despite bearing the main burden of HCC, prospective studies from developing countries are lacking. This prospective observational study was designed to estimate the incidence of HCC among Indian patients with hepatic cirrhosis. METHODS: Between April 2001 and November 2004, we enrolled 301 patients with liver cirrhosis. Patients found to be free of HCC using baseline abdominal ultrasound, triple-phase computed tomography (TPCT) and serum alpha-fetoprotein (AFP) levels were followed up prospectively for detection of HCC using ultrasound and AFP every 6 months, and TPCT annually. RESULTS: Among the 194 patients (mean age [SD] 45.1 [+/-13.1] years; male:female 6.1:1.0) followed up, 154 had Child's A and 40 had Child's B disease. The causes of cirrhosis were: hepatitis B-71 (36.6%), hepatitis C-54 (27.8%), dual infection with hepatitis B and C-12 (6.2%) and others including autoimmune, alcoholic and cryptogenic cirrhosis 57 (29.4%). During a cumulative follow up period of 563.4 person-years, 9 cases of HCC were detected, with an incidence rate of 1.60 per 100 person-years. CONCLUSION: In our study, the incidence of HCC among patients with liver cirrhosis was intermediate, being lower than that in Japan but higher than that reported from Europe.

KIRTDA, DRACHARYAS.  2007.  Goyal R, Chalamalasetty SB, Madan K, Paul SB, Arora R, Safaya R, Acharya SK.Acral and palmo-plantar hyperpigmentation in a patient with disseminated hepatocellular carcinoma.Indian J Gastroenterol. 2007 Nov-Dec;26(6):292-3.. Indian J Gastroenterol. 2007 Nov-Dec;26(6):292-3.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Capecitabine (5-fluorouracil prodrug) is being evaluated for the management of hepatocellular carcinoma, and is associated with a peculiar skin reaction called hand and foot syndrome (HFS). We describe one patient with HCC and drug-induced HFS.
KIRTDA, DRACHARYAS.  2007.  Role of surface promoter mutations in hepatitis B surface antigen production and secretion in occult hepatitis B virus infection. J Med Virol. 2007 Jan 23;79(3):220-228. J Med Virol. 2007 Jan 23;79(3):220-228. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
The production, secretion, and localization of surface proteins of hepatitis B virus (HBV) and the ratio of large to small surface protein S was studied in HepG2 cells transfected with the wild-type and mutant pre-S1 and pre-S2/S promoters of HBV molecular clones 313.1 (GenBank accession no. AY161147) and 761.1 (GenBank accession no. AY161159) from two patients with occult HBV infection. Fusion constructs were made by in frame fusion of the wild-type surface gene to the mutant pre-S1 and pre-S2/S promoters and wild-type promoter so that the structural part of the small surface protein remains identical. HepG2 cells transfected transiently were used for analysis. HBV surface proteins production and secretion was determined by enzyme linked immuno assay (ELISA) and localization by immunofluorescence. Immunoprecipitation of the large, middle, and small surface protein was carried out in transient transfected and metabolically labeled cells to determine the ratio of the large to small surface protein. The results indicate that HepG2 cells transfected with mutant HBV promoters had reduced HBV surface proteins secretion compared to wild-type HBV. HepG2 cells transfected with mutant HBV pre-S1 and pre-S2/S promoters showed cytoplasmic aggregation of HBV surface proteins compared to wild-type HBV promoters, which showed diffuse cytoplasmic localization. In all cases, the HBV surface proteins localized to the endoplasmic reticulum. The ratio between the large and small surface protein was 1.89 and 0.56 with mutant HBV 313.1 and 761.1 pre-S1 and pre-S2/S promoters, respectively, compared to 0.17 in wild-type. Thus, the aggregation of surface proteins, altered ratio and secretion of surface proteins were possibly the causes of occult hepatitis B infection. J. Med. Virol. 79:220-228, 2007. (c) 2007 Wiley-Liss, Inc.

2006

KIRTDA, DRACHARYAS.  2006.  Bose B, Khanna N, Acharya SK, Sinha S.Generation and characterization of a high-affinity chimaeric antibody against hepatitis B surface antigen.Biotechnol Appl Biochem. 2006 Feb;43(Pt 2):93-101.. Biotechnol Appl Biochem. 2006 Feb;43(Pt 2):93-101.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Antibody against HBsAg (hepatitis B surface antigen) is advocated for the passive immunotherapy in certain cases of hepatitis B infections. A recombinant monoclonal antibody against HBsAg would offer several advantages over the currently used polyclonal human hepatitis B immunoglobulin. 5S is a mouse monoclonal antibody that binds to HBsAg with very high affinity. However, this mouse antibody cannot be used for therapeutic purposes, as it may elicit antimouse immune responses. Chimaerization, by replacing mouse constant domains with human counterparts, can reduce the immunogenicity of this molecule. We have cloned the V(H) (heavy-chain variable region) and V(L) (light-chain variable region) genes of this mouse antibody, and fused them with C(H)1 (heavy-chain constant domain 1) of human IgG1 and C(L) (light-chain constant domain) of human kappa chain respectively. These chimaeric genes were cloned into a mammalian expression vector (pFab-CMV), which has a modular cassette coding for part of the hinge, C(H)2 and C(H)3 of human IgG1. The recombinant construct was transfected in CHO (Chinese-hamster ovary) cells to generate a stable transfectoma. The resulting transfectoma was maintained in a serum-free medium and the full-length chimaeric anti-HBsAg antibody was purified from the culture supernatant. The yield of the purified chimaeric antibody was moderate ( approximately 5.5 mg/l). We further characterized the chimaeric antibody using several in vitro techniques. It was observed that the chimaeric molecule was glycosylated and expressed in the expected heterodimeric form. This chimaeric antibody has very high affinity and specificity, similar to that of the original mouse monoclonal antibody.
KIRTDA, DRACHARYAS.  2006.  Madan K, Batra Y, Gupta SD, Chander B, Rajan KD, Tewatia MS, Panda SK, Acharya SK.Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians.World J Gastroenterol. 2006 Jun 7;12(21):3400-5.. World J Gastroenterol. 2006 Jun 7;12(21):3400-5.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
{ AIM: To evaluate the clinical and biochemical profile of patients with non alcoholic fatty liver disease (NAFLD) and to assess their histological severity at presentation. METHODS: Consecutive patients presenting to the liver clinic of All India Institute of Medical Sciences (AIIMS) with raised transaminases to at least 1.5 times upper limit of normal, and histologically confirmed non-alcoholic fatty liver disease were included. Patients who had significant alcohol intake or positive markers of other liver diseases or who were taking drugs known to produce fatty liver were excluded. The clinical, biochemical and histological profile of this group was studied. RESULTS: Fifty-one patients with NAFLD formed the study population. Their median age and BMI were 34(17-58) years and 26.7(21.3-32.5) kg/m(2) respectively and 46 (90.1%) were males. The majority of the patients had mild inflammation, either grade 1 [32 (63%)] or grade 2 [16 (31%)] and only 3 (6%) patients had severe (grade 3) inflammation. Twenty-three (45%), 19 (37%), 8(16%) and 1(2%) patient had stage 0, 1, 2 and 3 fibrosis respectively on index biopsy and none had cirrhosis. On univariate analysis, triglyceride levels more than 150 mg % (OR = 7.1; 95% CI: 1.6-31.5
KIRTDA, DRACHARYAS.  2006.  Kumar A, Bal C, Srivastava DN, Thulkar SP, Sharma S, Acharya SK, Duttagupta S.Management of multiple intrahepatic recurrences after radiofrequency ablation of hepatocellular carcinoma with rhenium-188-HDD-lipiodol.Eur J Gastroenterol Hepatol. 2006 Feb;18(. Eur J Gastroenterol Hepatol. 2006 Feb;18(2):219-23.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
We tried to evaluate the role of dosimetry-guided transarterial radionuclide therapy (TART) with rhenium-188 (Re-188)-4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)-lipiodol in a patient with multiple intrahepatic recurrences after radiofrequency ablation of hepatocellular carcinoma (HCC). The dosimetry helped in delivering the maximum possible activity of Re-188, thus the radiation-absorbed dose, safely to the tumour without jeopardizing other organs. There was no procedure-related complication and the patient tolerated therapy well with no adverse effects. The lesions were completely ablated with a single dose of Re-188 and the patient has been disease free for the past 18 months. TART with Re-188-HDD-lipiodol appears to be a promising therapeutic option in patients with HCC who experience recurrence after percutaneous ablative therapy.
KIRTDA, DRACHARYAS.  2006.  Bose B, Khanna N, Acharya SK, Sinha S.Generation and characterization of a single-gene mouse-human chimeric antibody against hepatitis B surface antigen.J Gastroenterol Hepatol. 2006 Sep;21(9):1439-47.. J Gastroenterol Hepatol. 2006 Sep;21(9):1439-47.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Antibody against hepatitis B surface antigen (HBsAg) is used for passive immunotherapy in certain cases of hepatitis B infection. The authors have earlier reported a high-affinity mouse monoclonal (5S) against HBsAg. However, this mouse antibody cannot be used for therapeutic purposes because it may elicit antimouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody. METHODS: A single-chain variable fragment (scFv), derived from the mouse monoclonal 5S, was fused with the fragment crystallisable (Fc) fragment of human IgG1. The scFv region is expected to bind to the antigen, whereas the Fc fragment can provide the effector functions required for virus neutralization. This chimeric molecule was expressed in Chinese hamster ovary (CHO) cells in serum-free medium. It was purified by affinity chromatography and characterized by in vitro binding studies. RESULTS: Purification and characterization indicated that this chimeric scFv-Fc fusion protein is secreted as a disulfide-linked, glycosylated, homodimeric molecule. The yield of the purified chimeric antibody was approximately 4.6 mg/L. In vitro analyses confirmed that this chimeric molecule retained the high affinity and specificity of the original mouse monoclonal. CONCLUSION: Because it is a single-gene product, this chimeric scFv-Fc has the advantage of stable expression. Being chimeric and bivalent, it is expected to be less immunogenic and therefore suitable for further in vivo studies on virus neutralization.
KIRTDA, DRACHARYAS.  2006.  Acharya SK, Panda SK.Hepatitis E virus: epidemiology, diagnosis, pathology and prevention.Trop Gastroenterol. 2006 Apr-Jun;27(2):63-8.. Trop Gastroenterol. 2006 Apr-Jun;27(2):63-8.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
HEV, a positive stranded RNA virus, is responsible for most of the epidemics of hepatitis in the developing world and is transmitted through contaminated water. It is the major aetiological agent for acute hepatitis and acute liver failure in endemic regions. It causes severe liver disease among pregnant females and patients with chronic liver disease. Serodiagnosis of HEV is now available and should be used routinely for diagnosis. The available evidence suggests that HEV may also be transmitted parenterally as well as vertically particularly in endemic areas. Experimental studies suggest that an HEV vaccine is a distinct possibility in the near future. In the absence of an effective vaccine, public health measures such as clean water supply, improved sanitation and public education are the major tools to prevent HEV epidemics in developing nations.
KIRTDA, DRACHARYAS.  2006.  Sugiyama M, Tanaka Y, Kato T, Orito E, Ito K, Acharya SK, Gish RG, Kramvis A, Shimada T, Izumi N, Kaito M, Miyakawa Y, Mizokami M.Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens.Hepatology. 200. Hepatology. 2006 Oct;44(4):915-24.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Various genotypes of the hepatitis B virus (HBV) induce liver disease of distinct severity, but the underlying virological differences are not well defined. Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3 each for Bj/B1 and C). HBV DNA levels in cell lysates, determined by Southern hybridization, were the highest for C followed by Bj/Ba and D/Ae (P < .01), and the lowest for Aa (P < .01), whereas in culture media, they were the highest for Bj, distantly followed by Ba/C/D and further by Ae/Aa (P < .01). The intracellular expression of core protein was more than 3-fold lower for Ae/Aa than the others. Hepatitis B e antigen (HBeAg) was excreted in a trend similar to that of HBV DNA with smaller differences. Secretion of hepatitis B surface antigen (HBsAg) was most abundant for Ae followed by Aa, Ba, Bj/C and remotely by D, which was consistent with mRNA levels. Cellular stress determined by the reporter assay for Grp78 promoter was higher for C and Ba than the other genotypes/subgenotypes (P < .01). Severe combined immunodeficiency mice transgenic for urokinase-type plasminogen activator (uPA/SCID), with the liver replaced for human hepatocytes, were inoculated with virions passed in mouse and recovered from culture supernatants. HBV DNA levels in their sera were higher for C than Ae by 2 logs during 4-7 weeks after inoculation. In conclusion, virological differences among HBV genotypes were demonstrated both in vitro and in vivo. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings.
KIRTDA, DRACHARYAS.  2006.  Acharya SK.HBV treatment: the hazy endpoint.Trop Gastroenterol. 2006 Jul-Sep;27(3):103-4.. Trop Gastroenterol. 2006 Jul-Sep;27(3):103-4.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies.
KIRTDA, DRACHARYAS.  2006.  Viral hepatitis in India. Natl Med J India. 2006 Jul-Aug;19(4):203-17.. Natl Med J India. 2006 Jul-Aug;19(4):203-17.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies.

2005

KIRTDA, DRACHARYAS.  2005.  Bhatia V, Singh R, Acharya SK.Predictive value of arterial ammonia for complications and outcome in acute liver failure.Gut. 2006 Jan;55(1):98-104. Epub 2005 Jul 15.. Gut. 2006 Jan;55(1):98-104. Epub 2005 Jul 15.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND AND AIMS: In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with ALF. METHODS: Eighty consecutive ALF patients admitted from March 2001 to December 2003 were followed up until death or complete recovery. All had arterial ammonia estimation at admission (enzymatic method). Logistic regression analysis was performed to identify independent predictors of mortality. RESULTS: Forty two (52.5%) patients died. Non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 micromol/l; p<0.001). An arterial ammonia level of > or = 124 micromol/l was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy. Patients with higher ammonia levels also developed more complications, including deeper encephalopathy (p = 0.055), cerebral oedema (p = 0.020), need for ventilation (p<0.001), and seizures (p = 0.006). Logistic regression analysis showed that pH, presence of cerebral oedema, and arterial ammonia at admission were independent predictors of mortality (odds ratios 6.6, 12.6, and 10.9, respectively). Incorporating these variables, a score predicting mortality risk at admission was derived: 2.53 + 2.91 ammonia + 2.41 oedema + 1.40 pH, where ammonia is scored as 0 (if <124 micromol/l) or 1 (if > or =124 micromol/l); oedema is scored as 0 (absent) or 1(present); and pH is scored as 1 (if < or =7.40) or 0 (if >7.40). Levels of partial pressure of ammonia were equally correlated with outcome. CONCLUSION: Arterial ammonia at presentation is predictive of outcome and can be used for risk stratification. Ammonia lowering therapies in patients with ALF should be evaluated.
KIRTDA, DRACHARYAS.  2005.  Prasad HK, Singhal A, Mishra A, Shah NP, Katoch VM, Thakral SS, Singh DV, Chumber S, Bal S, Aggarwal S, Padma MV, Kumar S, Singh MK, Acharya SK.Bovine tuberculosis in India: potential basis for zoonosis.Tuberculosis (Edinb). 2005 Sep-Nov;85(5-6):421-8. Ep. Tuberculosis (Edinb). 2005 Sep-Nov;85(5-6):421-8. Epub 2005 Oct 25.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Our laboratory has designed a specific nested-PCR (N-PCR) assay, based on the hupB gene of Mycobacterium tuberculosis (Rv2986c) and Mycobacterium bovis (Mb3010c) as a method to differentiate these closely related species. The present paper deciphers the utility of this assay for identification of pathogenic Mycobacteria in clinical samples. Extra-pulmonary clinical samples obtained from cattle and humans were investigated. Pre-dominance of M. tuberculosis (15.7%) and M. bovis (26.8%) was seen in humans and cattle, respectively. However, more importantly, both mycobacterial pathogens (mixed infection) were identified in a number of samples. In humans 8.7% of the samples and 35.7% in cattle were classified as mixed infection. The detection of mixed infection with the mycobacterial pathogenic duo in humans and bovines denotes the prospect of potential transmission of these pathogens from humans to cattle (zoonosis) and vice versa (reverse zoonosis).
KIRTDA, DRACHARYAS.  2005.  Pal S, Sahni P, Pande GK, Acharya SK, Chattopadhyay TK.Outcome following emergency surgery for refractory severe ulcerative colitis in a tertiary care centre in India.BMC Gastroenterol. 2005 Nov 30;5:39.. BMC Gastroenterol. 2005 Nov 30;5:39.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Steroid-based intensive medical therapy for severe ulcerative colitis is successful in 60-70% of such patients. Patients with complications or those refractory to medical therapy require emergency colectomy for salvage. Little is known about the impact of timing of surgical intervention and surgical outcomes of such patients undergoing emergency surgery in India where the diagnosis is often delayed or missed in patients who are poor, malnourished and non-compliant to medical treatment. METHODS: The clinical records of all patients undergoing emergency surgery for severe ulcerative colitis or its complication in the Department of GI surgery AIIMS, New Delhi, India, between January 1985 and December 2003 were retrieved and data pertaining to demographic features, duration of intensive medical therapy, presence of complications, time from admission to emergency surgery, surgical procedure, in-hospital morbidity and mortality and follow up status extracted. RESULTS: A total of 72 patients underwent emergency surgery (Subtotal colectomy: 60; ileostomy alone under local anaesthesia: 12). Poor nutritional status was seen in 61% of the patients. Twenty-one patients (29%) underwent emergency surgery for complications of severe ulcerative colitis such as colonic perforation (spontaneous 6, iatrogenic 4), massive lower gastrointestinal haemorrhage (5), toxic megacolon (4) and large bowel obstruction (2). The remaining patients (n = 51) underwent emergency surgery following failed intensive therapy; 17 underwent surgery < or = 5 days (Group I) and 34 were operated > 5 days (Group II) after initiation of intensive therapy. In this group all the post-operative deaths (n = 8) occurred in those who were operated after 5 days. The difference in mortality in these two groups (i.e. surgical intervention < or = or > 5 days) was statistically significant {0/17 (Group I) vs 8/34 (Group II); p = 0.03}. Overall, 12 patients died (in-hospital mortality: 16.7%). The mortality was higher (10/43; 23.3%) in our early experience (i.e. 1985-1995) when compared to our subsequent experience (2/29; 6.9%) (1996-2003). A total of 48 patients (including 3 awaiting a restorative procedure) are alive on follow up (66.7%; 3 patients lost to follow up). A restorative procedure could be successfully completed in 81% of the survivors of the emergency procedure. CONCLUSION: To optimize the outcome, a combined team of physicians and surgeons should be involved in the management of patients with severe ulcerative colitis with focus on nutritional support, correction of metabolic derangements, close clinical monitoring and timely assessment for the need for emergency surgery. This retrospective analysis shows that improved results can be achieved with experience and by following a policy of early surgical intervention within 5 days, especially in patients who have failed intensive medical therapy.
KIRTDA, DRACHARYAS.  2005.  Madan K, Batra Y, Gupta DS, Chander B, Anand Rajan KD, Singh R, Panda SK, Acharya SK.Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease.Indian J Gastroenterol. 2005 Nov-Dec;24(6):251-5.. Indian J Gastroenterol. 2005 Nov-Dec;24(6):251-5.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and weight management programs among patients with nonalcoholic fatty liver disease (NAFLD) are lacking. AIM: To find an effective single agent or combination of agents for management of NAFLD. METHODS: In this retrospective study, consecutive patient with histologically confirmed NAFLD with raised ALT were included. The patients received either weight management (exercise and therapeutic lifestyle changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I) ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA + vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT. RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were included between 1996 and 2004. All patients in group III normalized their ALT levels, which was significantly higher than numbers in group I (8/18) and group II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]); (p=0.01). Type of therapy received was the only factor predictive of ALT normalization. CONCLUSION: Combination regimen containing vitamin E appears to be effective in normalizing ALT among NAFLD patients.
KIRTDA, DRACHARYAS.  2005.  Acharya SK.Management of chronic hepatitis B: the Indian perspective. Trop Gastroenterol. 2005 Oct-Dec;26(4):171-2.. Trop Gastroenterol. 2005 Oct-Dec;26(4):171-2.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody. METHODS: We cloned the V(H) and V(L) genes of this mouse antibody, and fused them with CH1 domain of human IgG1 and C(L) domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. coli. RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal. This chimeric antibody fragment was further expressed in different strains of E. coli to increase the yield. CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a full-length chimeric antibody for therapeutic uses.
KIRTDA, DRACHARYAS.  2005.  High affinity mouse-human chimeric Fab against hepatitis B surface antigen. World J Gastroenterol. 2005 Dec 28;11(48):7569-78. ;21(9):1439-47.. World J Gastroenterol. 2005 Dec 28;11(48):7569-78. ;21(9):1439-47.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody. METHODS: We cloned the V(H) and V(L) genes of this mouse antibody, and fused them with CH1 domain of human IgG1 and C(L) domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. coli. RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal. This chimeric antibody fragment was further expressed in different strains of E. coli to increase the yield. CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a full-length chimeric antibody for therapeutic uses.

2004

KIRTDA, DRACHARYAS.  2004.  Bhatia V, Batra Y, Acharya SK.Prophylactic phenytoin does not improve cerebral edema or survival in acute liver failure–a controlled clinical trial.J Hepatol. 2004 Jul;41(1):89-96.. J Hepatol. 2004 Jul;41(1):89-96.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND/AIMS: Seizure activity in patients with acute liver failure (ALF) may increase cerebral oxygen requirements and worsen cerebral edema. Recently, prophylactic phenytoin has been recommended to suppress sub-clinical seizure activity evident on electroencephalographic monitoring. To determine the clinical utility of prophylactic phenytoin therapy in patients with ALF. METHODS: Forty two patients with ALF were randomized. Twenty two patients were given prophylactic phenytoin and 22 patients acted as controls. The baseline clinical and biochemical features were similar in the two groups and patients with > or =2 poor prognostic variables were equally represented. RESULTS: Sixteen patients in the phenytoin group, and 15 in the control group developed cerebral edema (P=0.38). Mechanical ventilation was required in 10 and 12 patients in the phenytoin and control groups, respectively, (P=0.77). Seizures occurred in 5 (22.7%) control patients and 5 (25%) phenytoin treated patients (P=0.86). Fourteen (70%) patients randomized to phenytoin and 15 (68.2%) control patients died (P=0.89). CONCLUSIONS: Seizure was common in patients with ALF. Prophylactic use of phenytoin did not prevent cerebral edema, seizures or need for mechanical ventilation, and did not improve survival.
KIRTDA, DRACHARYAS.  2004.  Hasegawa I, Tanaka Y, Kramvis A, Kato T, Sugauchi F, Acharya SK, Orito E, Ueda R, Kew MC, Mizokami M.Novel hepatitis B virus genotype a subtyping assay that distinguishes subtype Aa from Ae and its application in epidemiological studies.J Virol. 2004 Jul;. J Virol. 2004 Jul;78(14):7575-81.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
The eight genotypes of hepatitis B virus (HBV) have different geographical distributions, virological characteristics, and clinical manifestations. A unique subtype of HBV genotype A (HBV/A) was reported in sub-Saharan Africa, raising the possibility that patients infected with this subtype (HBV/Aa ["a" for African and Asian]) may have different clinical outcomes than other HBV/A isolates (HBV/Ae ["e" for European]). Comparison between 30 HBV/Aa and 30 HBV/Ae isolates indicated that almost all HBV/Ae isolates had G at nucleotide (nt) 1809 and C at nt 1812, whereas HBV/Aa isolates had T1809/T1812. Taking advantage of these two single nucleotide polymorphisms (SNPs), a novel subtype-specific PCR assay in the X/precore/core region was developed. This assay was combined with a restriction fragment length polymorphism assay using BglII in a different region (nt 1984 to 1989), which has a SNP distinguishing HBV/Aa from HBV/Ae, resulting in 100% specificity for the combined assay. Application of the subtyping assay using sera from 109 paid donors in the United States indicated significantly different distributions of HBV/A subtypes among races; African-Americans, Caucasians, and Hispanics had HBV/Ae, whereas Asians had mainly HBV/Aa, suggesting that the HBV/Aa isolates may have been imported by recent immigration from Asia. In conclusion, the specificity and sensitivity of the combined subtyping assay were confirmed, and its usefulness was demonstrated in a practical context.
KIRTDA, DRACHARYAS.  2004.  Hazari S, Panda SK, Gupta SD, Batra Y, Singh R, Acharya SK.Treatment of hepatitis C virus infection in patients of northern India.J Gastroenterol Hepatol. 2004 Sep;19(9):1058-65.. J Gastroenterol Hepatol. 2004 Sep;19(9):1058-65.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract

BACKGROUND AND AIM: The purpose of the present study was to evaluate the therapeutic response of north Indian patients with chronic hepatitis C (CH-C) to two different treatment regimens of interferon and ribavirin. METHODS: Consecutive patients with a diagnosis of CH-C attending the Liver Clinic at the All India Institute of Medical Sciences, New Delhi between April 1999 and April 2002 were included in the study. A competitive reverse transcription-polymerase chain reaction (RT-PCR) method developed in the authors' laboratory was used for quantification of hepatitis C virus (HCV)-RNA. Genotyping of HCV was also determined. The clinical, biochemical, virological and histological parameters were used to assess the therapeutic response among a clinical cohort of patients with chronic hepatitis C. They were treated with two different protocols (interferon [IFN]-alpha-2b, 3 million units daily and ribavirin 10.6 mg/kg daily in two divided doses for 6 months or IFN-alpha-2b, 3 million units thrice weekly and ribavirin 10.6 mg/kg daily for 6 months). RESULTS: Sixty-five patients with CH-C were included in the study. Blood transfusion (n = 28, 43%) and community-acquired (n = 23, 35%) HCV infections were the commonest. The mean HCV load was high (24.14 +/- 12.5 x 10(8) copies/mL). Genotype 2 and 3 were prevalent in 80% (41/51) of the patients. Forty-five patients received 3 million units of IFN thrice weekly and 20 received the same dose daily. All received the same dose of ribavirin. A sustained virological response (SVR) of 95% (19/20) was achieved among patients receiving daily IFN, whereas 64.4% (29/45) of those who received IFN thrice weekly had SVR. The virological relapse was significantly lower among patients who received daily IFN than in those treated with thrice weekly IFN (n = 1/20, 5% vs 10/39, 25.6%; P = 0.015). The proportion of patients receiving daily IFN among those achieving SVR (19/48, 40%) was significantly higher than the proportion of patients receiving similar therapy among patients without SVR (1/17, 6%; P = 0.02). CONCLUSIONS: Transfusion and community-acquired HCV infection were the major causes of CH-C. Genotype 2 and 3 HCV were most prevalent among these patients. Despite high viral load, these patients responded well to a combination of daily IFN-alpha-2b and ribavirin. Copyright 2004 Blackwell Publishing Asia Pty Ltd

KIRTDA, DRACHARYAS.  2004.  Batra Y, Dutta AK, Acharya SK.Molecular adsorbent and re-circulating system.Trop Gastroenterol. 2004 Apr-Jun;25(2):60-4.. Trop Gastroenterol. 2004 Apr-Jun;25(2):60-4.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
The molecular adsorbent recirculating system (MARS) is a non-biological artificial liver support system. Used for almost a decade, there are only two randomized controlled trials on the efficacy of MARS till date. A number of uncontrolled studies have documented a marked improvement in the biochemical parameters of patients after MARS. Although MARS seems to be an effective and promising tool in the management of liver failure, its cost needs to be reduced to enable it use in a member of indications.
KIRTDA, DRACHARYAS.  2004.  Tanaka Y, Hasegawa I, Kato T, Orito E, Hirashima N, Acharya SK, Gish RG, Kramvis A, Kew MC, Yoshihara N, Shrestha SM, Khan M, Miyakawa Y, Mizokami M.A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae. Hepatology. 2004 Sep;40(3):747-55.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
There are two subtypes of hepatitis B virus genotype A (HBV/A) and they are provisionally designated Aa ("a" standing for Africa/Asia) and Ae ("e" for Europe). In a case-control study, 78 HBV/Aa, 78HBV/Ae, and 78HBV/D carriers from several countries were compared. The prevalence of HBe antigen (HBeAg) in serum was significantly lower in carriers of HBV/Aa than in carriers of HBV/Ae (31% vs. 49%; P = .033), with a difference more obvious in the carriers aged 30 years or younger (34% vs. 67%; P = .029). HBV DNA levels in the carriers of HBV/Aa (median, 3.46 log copies/mL; 95% CI, 2.93-3.95) were significantly lower than those of carriers of HBV/Ae (6.09 log copies/mL; 95% CI, 4.24-7.64) or of carriers of HBV/D (5.48 log copies/mL; 95% CI, 4.06-7.02), regardless of the HBeAg status (P < .001). The most specific and frequent substitutions in 54 HBV/Aa isolates were double substitutions for T1809 (100%) and T1812 (96%) immediately upstream of the precore initiation codon, which would interfere with the translation of HBeAg in HBV/Aa infections. They were not detected in 57 HBV/Ae or 61 HBV/D isolates examined. The double mutation in the core promoter (T1762/A1764) was more frequent in both HBV/Aa (50%) and HBV/Ae (44%) than in HBV/D isolates (25%; P < .01), whereas the precore mutation (A1896) occurred in HBV/D isolates only (48%; P < .0001). In conclusion, the clearance of HBeAg from serum may occur by different mechanisms in HBV/Aa, HBV/Ae, and HBV/D infections, which may influence clinical manifestations in the Western countries where both genotypes A and D are prevalent. Copyright 2004 American Association for the Study of Liver Diseases
KIRTDA, DRACHARYAS.  2004.  Madan K, Batra Y, Panda SK, Dattagupta S, Hazari S, Jha JK, Acharya SK.Role of polymerase chain reaction and liver biopsy in the evaluation of patients with asymptomatic transaminitis: implications in diagnostic approach.J Gastroenterol Hepatol. 2004 Nov;. J Gastroenterol Hepatol. 2004 Nov;19(11):1291-9.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND AND AIM: Detection of an asymptomatic rise in the hepatic aminotransferase (ARHA) value has become a distinct and frequent clinical problem. We evaluated a three-step diagnostic algorithm in such patients for maximum yield. METHODS: Consecutive patients with an ARHA value 1.5-fold the upper limit of normal for at least 4 weeks and who were apparently healthy were included in the study. Each patient underwent standard biochemical investigations and a stepwise investigative protocol. In the first step, serological markers for hepatitis viruses, serum ferritin, 24-h urinary copper, alpha-1-antitrypsin phenotyping, and autoimmune markers were carried out. In step two, patients who tested negative for all the above markers had polymerase chain reaction (PCR) analysis for hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA. Patients without a diagnosis despite the above investigations underwent a liver biopsy as part of step three. RESULTS: Of 105 patients with ARHA, 38 were excluded for various reasons and 67 were included for the final analysis. The mean age was 35.11 +/- 11.96 years and 56 patients were men. The mean body mass index was 24.17 +/- 3.2 kg/m(2). The stepwise diagnostic algorithm achieved a diagnosis in 65/67 (97%) patients. Non-alcoholic steatohepatitis (NASH) and chronic viral hepatitis were the most common diagnoses, in 24 (36%) patients each. Using the diagnostic algorithm a diagnosis was reached in 34% of patients with only serological and biochemical investigations, whereas PCR for HBV and HCV could further detect the presence of active HBV or HCV viremia in 21% (14/97) and a liver biopsy was necessary to establish the diagnosis in 28/67 (42%) patients. CONCLUSIONS: A stepwise diagnostic algorithm in patients with ARHA resulted in an optimal use of PCR and invasive tests such as liver biopsy. Cryptic HBV and HCV infection was frequent among these patients and PCR was necessary in such cases. NASH and chronic viral hepatitis were the most frequent causes of ARHA.
KIRTDA, DRACHARYAS.  2004.  Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK.Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter.Gastroenterology. 2004 Nov;127(5):1356-71. Gastroenterology. 2004 Nov;127(5):1356-71. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND AND AIMS: Genome sequence of hepatitis B virus (HBV) from occult chronic infection is scarce. Fifty-six (9.4%) of 591 patients seronegative for hepatitis B surface antigen (HBsAg) with chronic liver disease were positive for HBV DNA. The complete HBV genome from 9 of these patients (S1-S9) and 5 controls positive for HBsAg (SWT.1-SWT.5) were analyzed. METHODS: Overlapping genome fragment amplification, cloning, and sequencing was performed on these cases. Functional analysis of surface promoter was conducted using fusion construct. RESULTS: All patients with occult infection except one (S8) had a low viral titer. Eight patients had infection with genotype A (S1-S5, SWT.1-2, SWT.5) and 6 had infection with genotype D (S6-S9, SWT.3-4). S4 and S5.1 of genotype A had the characteristic nucleotide deletions in core and pre-S1 region seen in genotype D. The major observations in patients with occult HBV infection were as follows: frequent quasispecies variation, deletions in pre-S2/S region affecting the surface promoters (nt 3025-54) and pre-S protein (S3, S5, S6, S8), truncated precore (S6, S8, S7.1) and core (S9) owing to stop signal, alternate start codon for the Polymerase gene (S3, S9), and YMDD mutation (S1, S4, S9) in patients not on antiviral therapy. HBsAg and core proteins could be shown immunohistochemically in 3 of 5 liver biopsy specimens available. The mutant surface promoters (pre-S2 and S) on functional analysis showed alterations in HBsAg expression. CONCLUSIONS: These changes in the regulatory region with possible alterations in the ratio of large and small surface proteins along with other mutations in the genome may decrease the circulating HBsAg level synergistically, making the immunodetection in serum negative.
KIRTDA, DRACHARYAS.  2004.  Prakash S, Dash SC, Kumar A, Dinda AK, Agarwal SK, Acharya SK.Frequency and role of hepatitis-C virus and type II cryoglobulinemia in membranoproliferative glomerulonephritis.J Assoc Physicians India. 2004 Jun;52:451-3.. J Assoc Physicians India. 2004 Jun;52:451-3.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Many studies have claimed a major role of chronic hepatitis-C virus (HCV) infection in immune-mediated diseases such as membranoproliferative glomerulonephritis (MPGN). Chronic HCV infection is also known to produce essential mixed cryoglobulinemia (EMC), which in turn may manifest as vasculitis and cryoglobulinemic MPGN. OBJECTIVE: The aim of the study therefore, was to determine frequency of association and pathogenetic role of HCV infection as well as that of EMC in MPGN patients. METHODS: Fifty-three adult patients of MPGN were studied for HCV, HBsAg, EMC, C3, anti-nuclear antibody (ANA), rheumatoid factor serologically. Histopathology, immunofluorescence (IF) were conducted in all patients and electron microscopy (EM) in those who were found HCV positive. Simultaneously 37 follow-up patients of HCV associated chronic hepatitis were investigated for EMC, renal functions and urinalysis done for evidence of glomerulonephritis (GN). RESULTS: Thirteen percent MPGN patients were HCV positive, however, no viral particle could be seen in electron microscopy in glomeruli of these patients. There was no serologic evidence of HCV induced immune complex GN. None of the MPGN patients showed cryoglobulinaemia. Similarly none from HCV associated chronic hepatitis group had EMC nor showed evidences of glumerulonephritis. CONCLUSION: Thirteen percent of adult MPGN patients in north India were seropositive for HCV, indicating significant association. However, clear evidence in favour of its pathogenetic role was lacking in our study. Secondly, this study reveals that MPGN is non-cryoglobulinemic and HCV is not a major cause in our population compared to what is reported from other countries. These observations need confirmation by a larger study.
KIRTDA, DRACHARYAS.  2004.  Development and evaluation of a quantitative competitive reverse transcription polymerase chain reaction (RT-PCR) for hepatitis C virus RNA in serum using transcribed thio-RNA as internal control. J Virol Methods. 2004 Mar 1;116(1):45-54.. J Virol Methods. 2004 Mar 1;116(1):45-54.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
A method for quantitation of hepatitis C virus (HCV) RNA was developed based on competitive reverse transcription polymerase chain reaction (RT-PCR) using in vitro transcribed mutated thio-RNA as a competitor template. The thio-RNA is more resistant to RNAse and is stable over a year. This assay was compared with the commercially available Roche Amplicor HCV Monitor assay V 2.0 and real time PCR using SYBR green 1 dye method. A total of 18 pre-therapy serum samples from chronic hepatitis C cases were tested in parallel by the three assays. All samples could be quantitated using the in-house competitive RT-PCR and real time PCR and there was a significant correlation in the virus titer (P<0.05). However, 8 (44%) samples could not be quantified by Amplicor HCV Monitor assay, which has a lower detection range (10(2) to 10(5.5) copies/ml). The in-house method of competitive RT-PCR showed a detection range of 10(3) to 10(10) copies/ml. In the patients the mean viral titer was found to be (9.66+/-9.3)x10(6) copies/ml. Ten (55%) of the samples, assessed by the Amplicor HCV Monitor assay showed a mean viral titre of (1.13+/-0.75)x10(6) copies/ml, which was lower than the other two tests. The competitive PCR method and real time PCR could amplify all prevalent genotypes. This in-house quantitative competitive RT-PCR method is simple, cheap, reproducible and useful for estimation of HCV RNA load.

2003

KIRTDA, DRACHARYAS.  2003.  Pati HP, Dayal S, Srivastava A, Pande GK, Acharya SK.Spectrum of hemostatic derangements, in Budd-Chiari syndrome.Indian J Gastroenterol. 2003 Mar-Apr;22(2):59-60.. Indian J Gastroenterol. 2003 Mar-Apr;22(2):59-60.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
BACKGROUND: Hemostatic abnormalities have been reported in various hepatocellular diseases. We evaluated the hemostatic functions in patients with Budd-Chiari syndrome. METHODS: Biochemical liver function tests, and measurement of prothrombin time, activated partial thromboplastin time, and plasma levels of anti-thrombin III (antigen) and activity of protein C were done in 36 patients with Budd-Chiari syndrome. RESULTS: Liver biochemistry was abnormal in 34 patients. Plasma prothrombin time and activated partial thromboplastin time were prolonged in 17 (47%) and 23 (64%) patients, respectively. Antithrombin III antigen levels and protein C activity were reduced in 15 (50%) and 25 (83%) patients, respectively, among the 30 patients studied. Albumin levels showed significant correlation with coagulation test results, levels of anti-thrombin-III, and protein C activity. CONCLUSION: Hepatic synthesis of coagulation factors and anticoagulants is reduced in Budd-Chiari syndrome; this may play a role in recurrence of thrombosis.
KIRTDA, DRACHARYAS.  2003.  Occult hepatitis B infection: the enigmatic virus.Indian J Gastroenterol. 2003 Jul-Aug;22(4):121-3.. Indian J Gastroenterol. 2003 Jul-Aug;22(4):121-3.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
We report a patient with fibrosing cholestatic hepatitis (FCH)-like syndrome in renal transplant recipient, who was negative for hepatitis-B and C-virus infection. The patient presented initially with extrahepatic biliary obstruction due to stricture at the lower end of the common bile duct. Cholestasis persisted inspite of effective biliary drainage. He was operated for empyema of the gallbladder and histological examination showed the presence of cytomegalovirus inclusions in the wall of the gallbladder. The patient died inspite of aggressive management; autopsy examination of the liver revealed evidence of FCH-like changes.
KIRTDA, DRACHARYAS.  2003.  Acharya SK, Batra Y.Is cirrhosis of the liver reversible? The ultimate that a hepatologist wishes.Trop Gastroenterol. 2003 Jan-Mar;24(1):1-2. Trop Gastroenterol. 2003 Jan-Mar;24(1):1-2.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
We report a patient with fibrosing cholestatic hepatitis (FCH)-like syndrome in renal transplant recipient, who was negative for hepatitis-B and C-virus infection. The patient presented initially with extrahepatic biliary obstruction due to stricture at the lower end of the common bile duct. Cholestasis persisted inspite of effective biliary drainage. He was operated for empyema of the gallbladder and histological examination showed the presence of cytomegalovirus inclusions in the wall of the gallbladder. The patient died inspite of aggressive management; autopsy examination of the liver revealed evidence of FCH-like changes.
KIRTDA, DRACHARYAS.  2003.  Duseja A, Nada R, Kalra N, Acharya SK, Minz M, Joshi K, Chawla Y.Fibrosing cholestatic hepatitis-like syndrome in a hepatitis B virus and hepatitis C virus-negative renal transplant recipient: a case report with autopsy findings.Trop Gastroenterol. 2003 J. Trop Gastroenterol. 2003 Jan-Mar;24(1):31-4.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
We report a patient with fibrosing cholestatic hepatitis (FCH)-like syndrome in renal transplant recipient, who was negative for hepatitis-B and C-virus infection. The patient presented initially with extrahepatic biliary obstruction due to stricture at the lower end of the common bile duct. Cholestasis persisted inspite of effective biliary drainage. He was operated for empyema of the gallbladder and histological examination showed the presence of cytomegalovirus inclusions in the wall of the gallbladder. The patient died inspite of aggressive management; autopsy examination of the liver revealed evidence of FCH-like changes.
KIRTDA, DRACHARYAS.  2003.  Bose B, Chugh DA, Kala M, Acharya SK, Khanna N, Sinha S.Characterization and molecular modeling of a highly stable anti-Hepatitis B surface antigen scFv.Mol Immunol. 2003 Dec;40(9):617-31.. Mol Immunol. 2003 Dec;40(9):617-31.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract

We raised a mouse monoclonal antibody (5S) against the 'a' epitope of the Hepatitis B surface antigen (HBsAg) by selecting for binding of the hybridoma supernatant in conditions that usually destabilize protein-protein interactions. This antibody, which was protective in an in vitro assay, had a high affinity with a relative dissociation constant in the nanomolar range. It also displayed stable binding to antigen in conditions that usually destabilize antigen-antibody interactions, like 30% DMSO, 8 M urea, 4 M NaCl, 1 M guanidium HCl and extremes of pH. The variable regions of the antibody were cloned and expressed as an single chain variable fragment (scFv) (A5). A5 had a relative affinity comparable to the mouse monoclonal and showed antigen binding in presence of 20% DMSO, 8 M urea and 3 M NaCl. It bound the antigen in the pH range of 6-8, though its tolerance for guanidium HCl was reduced. Sequence analysis demonstrated a significant increase in the frequency of somatic replacement mutations in CDRs over framework regions in the light but not in the heavy chain. A comparison of the molecular models of the variable regions of the 5S antibody and its germ-line precursor revealed that critical mutations in the heavy and light chains interface resulted in better inter-chain packing and in the movement of CDR H3 and CDR L1 from their germline positions, which may be important for better antigen binding. In addition to providing a reagent for neutralizing for the virus, such an antibody provides a model for the evolution of stable high affinity interaction during antibody maturation.

KIRTDA, DRACHARYAS.  2003.  Saraya A, Acharya SK, Vashisht S, Tandon RK.A pancreaticographic study of malnutrition-related diabetes mellitus.Trop Gastroenterol. 2003 Jul-Sep;24(3):120-3.. Trop Gastroenterol. 2003 Jul-Sep;24(3):120-3.. : The Icfai University Journal of Architecture, Vol. II No.1, February 2010 Abstract
Pancreatic involvement is considered to be the hallmark of malnutrition-related diabetes mellitus (MRDM). Of the 2 subgroups of the disease, fibrocalculous pancreatic diabetes (FCPD) is characterized by pancreatic calcification. The nature of pancreatic abnormalities in MRDM have not been studied extensively in Indian patients. The present study was designed to compare pancreatic abnormalities (exocrine and endocrine) including endoscopic retrograde pancreaticography in patients with FCPD and protein deficient pancreatic diabetes (PDPD), in relation to controls. Ten patients each of FCPD and PDPD were studied with regard to clinical features, biochemical exocrine and endocrine pancreatic responses, C-peptide response, islet cell antibody, and pancreatographic changes. Five normal pancreatograms were taken as control. Clinical and biochemical features in patient with FCPD and PDPD were as follows: pain in 8 and 2 patients, respectively; the mean duration of diabetes was similar in both groups (62.28 +/- 71.92 months V. 72 +/- 50.9 months); and faecal fat excretion and insulin requirements were comparable in both groups. The main pancreatic duct was dilated in 6 of 10 patient with FCPD and only 1 of 10 with PDPD on ultrasonography. On pancreatography the duct was dilated in 9 of 10 patients with FCPD and only 1 of 10 patients with PDPD. The number of side branches was reduced in all cases with MRDM; in those with FCPD, these were stunted and dilated while in PDPD side branches are thin and spastic. We conclude that pancreatic ductal changes involving the main duct and side branches are more frequent in patients with FCPD as compared to those with PDPD.

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