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Puja Sakhuja

Publications and source records attributed to Puja Sakhuja.

13 recordsLinked to original sources
PubMed2006

Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease.

Hepatitis C virus (HCV) genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied. HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index < or =5 and/or fibrosis < or =2) or severe (histological activity index > or =6 and/or fibrosis > or =3) liver disease. Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33% of hepatocytes affected), 2 (33%-66% of hepatocytes affected), or 3 (>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and un-subtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and un-subtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%, 4b:0.3%, 4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients. The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade > or =2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes. In conclusion, genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis.

Adolescent↗
PubMed2006

Basal core promoter, precore region mutations of HBV and their association with e antigen, genotype, and severity of liver disease in patients with chronic hepatitis B in India.

Spontaneous mutations of hepatitis B virus (HBV) could influence the severity of liver disease. Since the basal core promoter (BCP) and the precore (Pc) regions are important for viral replication, these regions were examined for naturally occurring mutations and were correlated with the genotype, e antigen status, and severity of liver disease. In 82 patients with histologically confirmed chronic hepatitis B, the BCP and Pc regions were sequenced and aligned with known wild-type sequences. Sequence based HBV genotyping was done and HBV DNA was quantified. Thirty-three (40%) patients had decompensated chronic liver disease and the remaining patients had chronic hepatitis B. Forty-six (56%) patients were HBeAg positive. HBV genotype A was found in 28%, D in 65%, and B/C in 7.3%. The Pc G1896A mutation was more common in HBeAg-negative (33% vs. 2%, P < 0.01) patients and was genotype D specific. The Pc G1862T mutation was detected more often in HBeAg-positive than HBeAg-negative (37% vs. 11%, P < 0.01) patients and was genotype A specific (P < 0.01). BCP mutations at the 1,762/64 nucleotide positions were common in HBeAg negative than positive (36% vs. 13%, P < 0.05) and were equally common in different genotypes. TA 1-3 region mutations of the BCP were significantly higher in HBeAg-negative as compared to HBeAg-positive patients (78% vs. 26%, P < 0.01). BCP mutations had significantly higher HBV DNA levels. It is concluded that Pc G1862T mutant is Genotype A-specific but is not always associated with e antigen. The TA 1-3 rich mutations of BCP region are also associated with the absence of e antigen in Indian patients.

Adolescent↗
PubMed2006

Primary biliary cirrhosis in India.

BACKGROUND: Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India. We analyzed the clinical, biochemical, serological and histological features of patients with PBC for over a 10-year period. METHODS: PBC was diagnosed by the presence of raised level of serum alkaline phosphatase (ALP), anti-mitochondrial antibody (AMA) positivity (1:40 dilution), and/or diagnostic liver histology. RESULTS: Fifteen female patients with mean age of 46.5+/-11 years were studied. Pruritus (80%) followed by jaundice (67%), skin changes (pigmentation, coarsening, xanthelesma and vitiligo) (67%) and fatigue (60%) were common symptoms. The mean duration of the symptoms was 3.5+/-5.4 years (3 months to 20 years). Dryness of eyes was observed in only 2 patients. Hepatomegaly was noted in 87% of the patients and ascites at presentation in 40%. Mean levels of bilirubin and albumin at the time of diagnosis were 3.4+/-3.3 mg/dl and 3.5+/-0.8 g/dl, respectively. The level of serum ALP ranged from 54 to 2400 IU/L, with a median being 552 IU/L (2 x ULN). In all the 15 patients with AMA positive, 8 (53%) were also positive for either anti-nuclear or anti-smooth muscle antibodies. Two patients presented with persistently elevated SAP after an acute hepatitic illness. Liver biopsy was available in 13 patients, diagnostic of PBC II & III (8) and with evidence of cirrhosis (5). Associated autoimmune disorders were observed in 5 patients (33%). The mean time for follow-up was 26+/-21 months (1 to 87 months). In 4 deaths, 3 were due to liver related causes. CONCLUSION: PBC is a rare cause of chronic liver disease in India. PBC in India, unlike in the West, presents late, often with features of cirrhosis and decompensation.

Adult↗
PubMed2006

Nonalcoholic steatohepatitis--a histological perspective.

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease that has gained recognition in the last two decades. It may even account for some of the cases previously diagnosed as cryptogenic cirrhosis. Association of this entity,with obesity, insulin resistance and type II diabetes is well documented. In this review we clarify the terminology and describe the histological features associated with NASH. Criteria for diagnosis, grading and staging systems and role of liver biopsy is also discussed.

Adult↗
PubMed2005

Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients.

BACKGROUND: Monotherapy with interferon (IFN) or lamivudine is effective in a limited proportion of chronic hepatitis B (CHB) patients. A sequential combination may have better therapeutic effects by sustained viral suppression combined with immunomodulation. AIM: To compare the efficacy of sequential lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB patients. PATIENTS AND METHODS: Seventy-five treatment naïve HBeAg positive patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 x ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added for 16 wks after the first 8 wks (group A, n = 38; age 30 +/- 12 yr; M:F = 35:3) or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 +/- 16 yr; M:F = 31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and analysis was done on intention-to-treat. Serial samples were studied for the emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing. RESULTS: At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%) in group B (p= 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA levels were seen in 26.3% and 13.5% (p= 0.249), respectively. Nine of 10 (90%) patients in group A and 1 of 5 (20%) in group B maintained the response through week 76 (p= 0.017). At week 76, 5 additional patients in group A and 3 in group B further achieved the primary end point and the overall HBeAg loss was observed in 44.7% and 18.9% (p= 0.025) and HBeAg loss, anti-HBe appearance, and undetectable hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B, respectively (p= 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and 16.2% in groups A and B, respectively (p= 0.039). Normal ALT was seen in 47.7% and 40.5% at week 52 (p= 0.489) and ALT was normal in 39.5% and 13.5% at week 76 (p= 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p= ns). The rate of histological improvement was comparable in the two groups. CONCLUSIONS: Our results demonstrate that sequential therapy is superior to lamivudine monotherapy in achieving sustained seroconversion, ALT normalization, and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian patients with CHB did not relapse after stopping lamivudine monotherapy.

Adolescent↗
PubMed2004

Factors predicting advanced hepatic fibrosis in patients with postcholecystectomy bile duct strictures.

HYPOTHESIS: Simplified evaluation based on clinical and biochemical variables might predict the degree of hepatic fibrosis in patients with postcholecystectomy bile duct strictures. DESIGN: Prospective cohort study. SETTING: Tertiary care referral and teaching hospital. PATIENTS: Sixty-four patients with postcholecystectomy bile duct strictures undergoing definitive repair. Prospectively collected information included demographics, disease-related characteristics, and serial liver function tests. Hepatic histologic features (fibrosis, cholestasis, portal inflammation, and ductular proliferation) were independently graded by 2 pathologists masked to clinical data using a previously validated scale. Patients were dichotomized into groups based on degree of hepatic fibrosis. Univariate and multivariate analyses were performed. MAIN OUTCOME MEASURE: Identification of variables that predict the presence of advanced hepatic fibrosis (grade 2-3). RESULTS: Thirty-five patients (55%) had early hepatic fibrosis (grade 0-1), and the remaining 29 (45%) had advanced fibrosis (grade 2-3). Univariate analysis demonstrated that duration of biliary obstruction, presence of portal hypertension, basal alanine aminotransferase (ALT) levels, and time to normalization of serum total bilirubin, ALT, and alkaline phosphatase levels after surgical drainage were statistically significantly associated with the presence of advanced hepatic fibrosis. However, multivariate analysis revealed that only duration of biliary obstruction (odds ratio [OR], 1.6048; P =.009), basal ALT levels (OR, 0.9634; P =.02), and time to normalization of ALT levels after surgical drainage (OR, 1.6680; P =.006) were significant predictors of advanced hepatic fibrosis. CONCLUSION: Duration of biliary obstruction, basal ALT level, and time to normalization of ALT level after surgical repair are independent predictors of advanced hepatic fibrosis (grade 2-3) in patients with postcholecystectomy bile duct strictures.

Adolescent↗
PubMed2004

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus.

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.

Alleles↗
PubMed2004

Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-alpha inhibitor could prove useful in treating patients with NASH. METHODS: Eighteen patients (mean age, 34 +/- 7.8 yr) with histologically proven NASH and with persistently elevated ALT (>1.5 times) were given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering agent or antioxidants were concurrently advised. RESULTS: Impaired fasting glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia were noted in 6, 35, 17, and 53% of the patients, respectively. After 6 months of therapy, fatigue improved (55.6 vs 20%, p= 0.016), but serum triglyceride (182 +/- 66 vs 160 +/- 55 mg/dl, p= 0.397), cholesterol (173 +/- 46 vs 162 +/- 40 mg/dl, p= 0.440), and body mass index (BMI) (27.3 +/- 3.1 vs 26 +/- 3.1 kg/m(2), p= 0.087) remained unchanged. Mean AST (66 +/- 29 vs 33 +/- 11 IU/l, p < 0.0001) and ALT (109 +/- 44 vs 47 +/- 20 IU/l, p < 0.0001) reduced significantly. ALT normalized in 23% at month 1 (p= 0.125), 35% at month 2 (p= 0.125), and 60% at month 6 (p= 0.008) of treatment. The insulin resistance index assessed by homeostatic metabolic assessment (HOMA(IR)) improved (5.1 +/- 3.4 vs 2.6 +/- 2, p = 0.046) and the serum TNF-alpha reduced significantly after therapy (22.15 +/- 2.49 vs 17 +/- 2.58 pg/ml, p = 0.011). The drug was well tolerated. CONCLUSIONS: In patients with NASH, pentoxifylline therapy effectively achieved significant clinical and biochemical improvement with reduction in HOMA(IR). These benefits are possibly mediated through suppression of TNF-alpha.

Adult↗
PubMed2004

Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection.

This study compares the histology of liver biopsies in precore mutant (PCM) and wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of wild-type HBV infection were included. Patients were diagnosed on the basis of serological profile and HBV DNA assessment. Liver biopsies in each case were assessed for histological activity and stage of fibrosis using a modification of Knodell's scoring system. There was no statistically significant (P=0.14) difference in histological activity in the two groups. The difference in stage of fibrosis in the two groups was statistically significant (P=0.001). Quantitative estimation of viral load did not show any correlation with liver histology. PCM HBV showed greater stage of fibrosis compared with wild-type infection, and this may be related to disease progression and lack of response to therapy.

Adult↗
PubMed2003

Primary rhabdoid tumor of the gallbladder: report of a case.

A 46-year-old man was operated on for cholelithiasis with chronic cholecystitis. On gross inspection of the resected gallbladder, a slight thickening in the body wall, in an area measuring about 1 x 0.5 cm, was noted. On light microscopic and immunohistochemical examinations, the lesion was diagnosed to be a rhabdoid tumor. After a thorough review of the literature we failed to find any reference to such a lesion in the gallbladder. This is the first known case report of a rhabdoid tumor of the gallbladder.

Gallbladder↗
PubMed2003

Histological profile of liver disease in patients with dual hepatitis B and C virus infection.

UNLABELLED: There is limited information on the histological profile of chronic liver disease due to dual infection with hepatitis B virus and hepatitis C virus infection. Few studies have indicated higher histological activity with dual infection as compared to HBV and HCV infection present alone. This study aims at reviewing the histological profile of liver biopsies in the three groups. Liver biopsies of 25 patients serologically diagnosed as HBV and HCV dual infection (Group I), were compared with 25 age and sex matched cases of HBV infection (Group II) and HCV infection (Group III). RESULTS: Mean Histological Activity Score in group I was 8, which was higher than the scores of group II (6.2) and group III (7.3). The mean stage of fibrosis was also slightly higher in group I (2.3) as compared to group II (1.9) and group III (1.7). However, when stage 3 and 4 fibrosis (extensive fibrosis) were combined and compared with the number of patients with stage 1 and 2 fibrosis in each group, we found Group I (dual infection) had larger number of patients with extensive fibrosis (48%) than in Groups II and III (20% and 36% respectively). In addition, there was no significant difference in presence of features like fatty change, bile duct injury and lymphoid aggregates in the three groups. CONCLUSION: Patients with dual HBV and HCV infection are more likely to have an advanced stage of disease than those with a single infection, however there is no significant difference in histologic activity or any other histological parameter between these groups.

Adult↗
PubMed2002

Profile of asymptomatic chronic HBV infection in India.

BACKGROUND & OBJECTIVES: In India, horizontal transmission in early childhood has been shown to be a significant mode of transmission of hepatitis B virus (HBV). This prospective, cross-sectional study was undertaken to study the biochemical, serological and histological profile of incidentally detected asymptomatic HBsAg positive subjects (IDAHS) picked up at a tertiary care referral centre. METHODS: In 157 (M:F::123:34) HBsAg positive subjects, clinical, biochemical, virological and histological assessment was done. The histological activity index (HAI) of > 3 was considered as chronic hepatitis. Serum was tested for HBsAg, HBeAg, HBeAb, HBV DNA and alanine transaminase (ALT). RESULTS: Seventy (45%) subjects were HBeAg and 83 (53%) anti-HBe positive. While 71 per cent of the subjects with elevated ALT had an HAI > 3, only 36 per cent with normal ALT showed significant histological changes (P < 0.001). Significant histopathological lesions in the liver biopsy were seen in 92 (59%) subjects, with moderate to severe lesions in 14. IDAHS who were HBeAg +ve were more likely to have significant histological lesion than those who were anti-HBe +ve (P < 0.01). In the anti-HBe +ve group, 35 of 57 (61%) subjects for whom HBV-DNA was available, were HBV-DNA positive. Anti-HBe+ve, HBV-DNA+ ve IDAHS with elevated ALT were more likely to have chronic hepatitis vis-a-vis those subjects in this group who had a normal ALT (P < 0.001). INTERPRETATION & CONCLUSION: ALT is a reliable discriminant of significant histological lesion in IDAHS. The relatively young mean age of Anti-HBe +ve IDAHS suggests an early age of infection and hence, early seroconversion or mutant virus infection in this cohort. A significant proportion of these IDAHS have HBV-DNA positivity and HAI > 3. Our results clearly demonstrate ongoing liver disease in asymptomatic, so-called "HBV carriers". We propose that the term hepatitis B 'carrier' should be abandoned and replaced by 'chronic HBV infection'.

Adolescent↗