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Subrat Kumar Acharya

Publications and source records attributed to Subrat Kumar Acharya.

17 recordsLinked to original sources

Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death.

BACKGROUND/AIMS: India is hyper-endemic for hepatitis E virus (HEV). HEV infection in cirrhosis may cause high mortality. Prospective study evaluating HEV infection in cirrhotics is scarce. METHODS: Consecutive patients with cirrhosis and healthy controls were included. Cirrhotics were categorized to 3 groups, (Group I - rapid decompensation, Group II - chronically decompensated, Group III - cirrhotics without decompensation). Sera from cirrhotics and controls were tested for HEV-RNA (RT-PCR). HEV-RNA positivity among cirrhotics and controls was compared. Natural course and mortality rate between HEV infected and non-infected cirrhotics were assessed during a 12-month follow-up. RESULTS: 107 cirrhotics and 200 controls were included. 30 (28%) cirrhotics and 9 (4.5%) controls had detectable HEV-RNA (p<0.001). HEV- RNA positivity among Group I (n=42), II (n=32) and III (n=33) cirrhotics was 21 (50%), 6 (19%) and 3 (10%), respectively (p=0.002). 70% (21/30) with HEV infection and 27% (21/77) without it had rapid decompensation (p=0.001). Mortality between HEV infected and non-infected cirrhotics at 4 weeks (43% vs. 22%, p=0.001) and 12 month (70% vs. 30%, p=0.001) was different. Multivariate analysis identified HEV infection, Child-Pugh's score, renal failure, and sepsis as independent factors for mortality. CONCLUSIONS: In India, cirrhotics were prone to HEV infection, which was associated with rapid decompensation and death.

Adult↗

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.

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.

Genotype↗

Prophylactic phenytoin does not improve cerebral edema or survival in acute liver failure--a controlled clinical trial.

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.

Adolescent↗

Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter.

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.

Adolescent↗

Treatment of hepatitis C virus infection in patients of northern India.

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.

Adult↗

Role of polymerase chain reaction and liver biopsy in the evaluation of patients with asymptomatic transaminitis: implications in diagnostic approach.

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.

Adolescent↗

Seroepidemiology of hepatitis A virus infection among school children in Delhi and north Indian patients with chronic liver disease: implications for HAV vaccination.

BACKGROUND: Universal vaccination against hepatitis A virus (HAV) has been recommended for children because of the changing epidemiological pattern of HAV. Vaccination has also been advised for patients with chronic liver disease as HAV superinfection in these patients can result in severe or even fatal disease. In India, the indications for HAV vaccination are not clear due to contradictory seroepidemiological data in children and lack of data on HAV seroprevalence in patients with chronic liver disease. METHODS: Sera were collected from children studying in two government-run schools and from patients with chronic liver disease attending the Liver Clinic at the All India Institute of Medical Sciences (AIIMS). The sera were tested for anti-HAV antibodies. The incidence of HAV-induced acute hepatitis and acute liver failure at AIIMS over the last 10 years was also assessed. RESULTS: A total of 93.2% (1328/1424) of the school children between 4-18 years of age who were included in the study had anti-HAV antibody in their sera. Eighty percent of the children had antibodies against HAV in their sera by the age of 5 years, whereas all the children above 16 years were positive for anti-HAV antibody. A total of 256 patients with chronic liver disease (94 with cirrhosis of the liver, 160 with chronic hepatitis) were tested for the presence of anti-HAV antibody. Of them, 97.6% (248/254) had anti-HAV antibody in their sera. The annual frequency of HAV-induced acute viral hepatitis and acute liver failure at AIIMS during the last 10 years did not show any change. CONCLUSION: Mass vaccination against HAV is not required in north India because of the presence of protective antibodies against HAV in the majority of the population.

Adolescent↗

Vaccination against hepatitis A virus may not be required for schoolchildren in northern India: results of a seroepidemiological survey.

OBJECTIVES: To evaluate the current seroprevalence of antibodies against hepatitis A virus (HAV) in a sample of schoolchildren above 10 years of age and to determine the prevalence of HAV-induced hepatitis in adults at a tertiary care hospital in northern India between January 1992 and December 2000. METHODS: Sera from 276 male and 224 female schoolchildren aged 10-17 years were tested for anti-HAV antibodies by enzyme-linked immunosorbent assay. Consecutive patients with a diagnosis of acute viral hepatitis who attended a liver clinic were tested for the serological markers of HAV, hepatitis B Virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus. FINDINGS: Of the male and female children, 96.3% and 98.2%, respectively had anti-HAV antibodies in their sera. The prevalence of these antibodies in the age groups 10-12, 13- 14, and 15-17 years were 98.6%, 94.8%, and 98.3% respectively. The frequency of HAV- induced acute viral hepatitis (69/870, 8%) in adults did not show an increasing trend. CONCLUSION: Mass HAV vaccination may be unnecessary in northern India because the seroprevalence of protective antibodies against HAV in schoolchildren aged over 10 years remains above 95% and there has been no apparent increase in HAV-induced acute viral hepatitis in adults.

Adolescent↗

Spectrum of hemostatic derangements, in Budd-Chiari syndrome.

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.

Budd-Chiari Syndrome↗

Molecular adsorbent and re-circulating system.

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.

Equipment Design↗

Hepatitis E virus: epidemiology, diagnosis, pathology and prevention.

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.

Genotype↗