Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B.This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months.Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histology activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively.Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.
Purpose: In virus-infected cells, pattern recognition receptors (PRRs) like Toll like receptor (TLR)-3 and RIG-I recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β (TRIF) which through TRAF6 induce the interferon. This study is designed to quantify TLR3, MAVS, TRIF and TRAF6 proteins from liver biopsies of chronic hepatitis C (CHC) cases. Methods: Liver tissue from 46 CHC and 12 healthy individuals were studied for the expression levels of TLR3, MAVS, TRIF and TRAF6 proteins using Semiquantitative Digital Image analysis, after specific detection of these proteins by western blotting followed by immune-detection based chemi-luminance. Results: Out of 46 CHC cases, 13 patients were female (28.26%) and 33 were male (71.73%). In CHC group treatment naïve patients were 39 (84.78%) and treated were 7 (15.22%). Out of these 7 patients, 4 (57.14%) were nonresponders. The TRAF6 expression increased in CHC (0.234±0.027) than healthy (0.212±0.025), whereas TRIF, TLR3 and MAVS were decreased (0.114±0.020, 0.108±0.015 and 0.067±0.012) than healthy individuals (0.142±0.018, 0.182±0.012 and 0.082±0.011). TRAF6 in treated patients (0.244±0.018) expressed less than treatment naïve (0.248±0.017). TRIF, TLR3 and MAVS in treated patients (0.096±0.003, 0.093±0.004 and 0.057±0.009) were significantly less than treatment naïve (0.124±0.018, 0.117±0.011 and 0.073±0.010). TRIF and TLR3 levels were significantly less in non-responders than responders (0.095±0.003, 0.092±0.005 and 0.097±0.004, 0.094±0.004). TRAF6 comes down slightly in responders (0.235±0.018) compared to nonresponder (0.246±0.021), whereas MAVS expression was high (0.070±0.003 and 0.053±0.004). Conclusion: Present preliminary data showed that the TLR3, TRIF, and MAVS protein levels are less in CHC cases and TRAF6 expression is increasing along with increase in liver inflammation.MAVS protein specially expressed at lower levels in all post-infected conditions except in responders, suggesting that the protein is most effected in persistance HCV infection, thus hampering the interferon inducing through cystolic pathway leading to progression of the disease.
The major causes of chronic liver disease (CLD) are infection with Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) either alone or together. The clinical course of the disease varies in cases ofcoinfection with HCV and HBV as compared to single infection. The present study was carried out to determine the occurrence of coinfection of HCV with HBV in CLD patients and to look for the presence of suppressive effect of the two viruses on each other. The severity of liver disease was also assessed and correlated with biochemical profiles. Sera from 150 patients of CLD were tested serologically for the presence of HBsAg, IgG anti HBc and anti-HCV antibodies. HBV DNA and HCV RNA were also detected by amplifying surface region and 5' noncoding-core region respectively by polymerase chain reaction. Forty-seven (31.3%) cases showed the presence of HBsAg or anti IgG-HBc or HBV DNA either alone or together (Group A). Thirty-nine (26%) cases were found to be positive for HCV by detecting either anti-HCV antibodies or HCV RNA (Group B). Coinfection ofHCV with HBV (Group C) could be detected in twenty-four (16%) cases, of these twenty-one cases (87.5%) were positive both for HCV RNA and IgG anti-HBc without the presence of HBV DNA whereas in none of the cases could HBV DNA be detected in the absence of HCV RNA. Forty (26.6%) cases had neither HCV or HBV related CLD. Amongst, the biochemical parameters, the liver function test profiles were altered and found to be statistically significantly in HCV positive cases (Group B) when compared to the negative ones while in case of HBV (Group A) and coinfected (Group C) cases none of the parameters was statistically significant when compared with non-HBV and non-coinfected cases respectively. Thus, coinfection of HCV with HBV is seen in a substantial number of CLD cases. It is also revealed from the present study that HCV infection has a suppressive effect on the replication of HBV as seen by the loss of replicative markers like HBV DNA.
Purpose: The study was designed to 1. Detect and characterize mutations in the precore/core and surface genes using PCR-SSCP of the hepatitis B virus and finally confirming by direct sequencing. 2. To study the clinical and biochemical profile and the final outcome of patients harboring mutant forms of the HBV virus and that of the wild type. Methods: The study included a total of 331 patients (Acute Viral Hepatitis: 115), (Fulminant Hepatitis: 40), (Chronic Hepatitis: 116), (Liver Cirrhosis: 30), (Hepatocellular carcinoma: 30) who were admitted in the wards of Lok Nayak Hospital, New Delhi, India. Surface, Pre-core and Core regions of the viral genome were amplified with the help of PCR. Surface, Pre-core and Core regions of the viral genome were screened for the presence or absence of mutations by SSCP. Ligase chain reaction was performed specifically for the presence or absence of W28 stop codon mutation. Purified products were sequenced with respect to the forward and reverse primers in an automated DNA sequencer. The obtained sequences of the above described regions of the viral genome were compared with reference strain from the Gene bank. Results: Precore, core and surface mutations accounted for 20% (23/115), 8.6% (10/115) and 9.5% (11/115) respectively in patients of acute viral hepatitis. Precore and core mutations accounted for 47.5% (19/40) of the fulminant hepatitis cases. Precore and core mutations accounted for 13.7% (16/116) while surface mutations accounted for 8.6% (10/116) of the cases of chronic hepatitis B. Precore and core mutations were observed in 46.6% (14/30) of the cases of HCC. Stop codon mutations were observed in all the categories. A clear association of genotype D and genotype A was documented in this particular study but the frequency of genotype D (70%) was higher compared to genotype A (30%) with response to the different types of liver diseases evaluated. Conclusion: 1) the study suggested that the prevalence of Precore mutation was significantly higher in fulminant hepatitis cases compared to acute viral hepatitis and chronic hepatitis. 2) the prevalence of Precore stop codon G1896 (W28 stop) was seen in all clinical categories and therefore it rules out its association with any particular spectrum of liver disease. 3) The study revealed that HBeAg does not necessarily associate with W28 stop mutations. 4) G1896 Precore mutation was specifically associated with genotype D. 5) Core gene mutations were found to have no genotype specificity. 6) Prevalence of genotype D was seen in 70% of the cases of different type of liver diseases while 30% were constituted by genotype A. 7) A118 and A128 surface mutants was specifically associated with genotype D.
Summary To study the role of heat shock protein A1L ( HSPA 1L) and A1B ( HSPA 1B) polymorphisms and subsequent risk of hepatocellular carcinoma ( HCC ) in India. Subjects enrolled included 185 cases of HCC , 182 cases of chronic hepatitis ( CH ) and 200 healthy controls. Genomic DNA was typed for HSPA 1L2437 and HSPA 1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. Other risk factors were also analysed. Hepatitis B virus ( HBV ) infection, older age >35 years and high aflatoxin level in urine increased the risk of HCC . The frequencies of HSPA 1L BB genotype and B allele in HCC were more than in CH [odds ratio ( OR ): 9.83; P = 0.000], but also in HBV ‐related HCC than Chronic Hepatitis B (CHB) [ OR : 3.44; P = 0.004] and HCV ‐related HCC compared to CHC [ OR : 6.32; P = 0.010]. The frequency of HSPA 1B genotype in the homozygous state was more in CH [ OR : 6.01; P = 0.001] and is a good marker to predict the risk of HCV ‐related CH ( CHC ) compared to controls. HCV ‐related HCC has a higher frequency of the B allele of HSPA 1B than healthy controls [ OR : 3.95; P = 0.000] and CHC [ OR : 2.35; P = 0.000], respectively. The frequencies increased further significantly in CHC compared to healthy controls [ OR : 9.26; P = 0.000]. The risk for the development of CH and HCC compared to healthy controls irrespective of the aetiology was significant in terms of the HSPA 1B marker than HSPA 1L in the Indian population.
Introduction: Hepatitis E virus (HEV) infection has distinct features, depending upon the genotype and geographical area. HEV genotypes 1 and 2 are endemic to various developing countries causing epidemics of acute viral hepatitis with human to human transmission. On the other hand, HEV genotypes 3 and 4 prevalent in developed countries commonly lead to subclinical infection and are transmitted zoonotically. HEV infection typically causes acute self-limiting illness associated with low morbidity and mortality. Infection with HEV genotype 1 or 2 in pregnancy, especially in the third trimester may lead to severe illness and fulminant liver failure. Poor maternal and fetal outcomes have been reported.Areas covered: This review highlights the various aspects of HEV infection in pregnancy including diagnosis, management, and prevention.Expert commentary: Treatment is mainly supportive with diligent monitoring and intensive care. Therapeutic termination of pregnancy cannot be recommended based to the available literature. Early liver transplantation (LT) should be considered in these patients although the indications and timing of LT are still controversial. Prevention of HEV infection or illness by improved sanitation and active/passive immunization needs further research.
*Senior Resident, **Post Graduate Student, ***Director Professor, †Professor, ‡Assistant Professor, Department of Medicine, Maulana Azad Medical College, New Delhi Received; 15.10.2013; Accepted: 27.11.2013 M soft tissue tumours of anterior abdominal wall is not a common ent i ty compris ing < 1% of adult mal ignant growths. 1 They arise from musculoaponeurotic fascia of anterior abdominal wall and are generally aggressive tumours with high incidence of local recurrence (25%) and propensity for distant metastases.2 They generally present as painless, rapidly growing abdominal wall mass which can cause complications when it involves the surrounding structures. Its presentation as gastrointestinal bleeding is extremely rare. We present a case of 40 year old non-alcoholic male, a diagnosed case of abdominal wall spindle cell tumour who had been operated twice in the last three years with wide local excision and skin grafting without any post-operative chemoradiotherapy, presented this time with swelling at the site of previous tumour excision for last six months and melaena for last one week. He complained of generalised weakness and weight loss for few months. There was no history of haematemesis, chest pain, dyspnoea or jaundice. On examination the patient was of average built. He was afebrile and haemodynamically stable. There was a firm soft tissue swelling on abdomen (10×10 cm size) with well def ined margin having superf ic ia l ulcerat ions. Invest igat ions showed microcytic hypochromic anaemia with deranged iron studies (S. Ferritin 47.37 ng/dl, TIBC-358.6 ng/dl). His liver and kidney function tests were within normal limits. CECT of abdomen and thorax was suggestive of a heterogeneous enhancing solid cystic mass lesion of anterior abdominal wall with abdominal and mediastinal extensions. UGI endoscopy was suggestive of mass lesion over anterior gastric wall (about 5 cm × 5 cm) with central ulceration. Endoscopic guided b iopsy f rom the mass was suggestive of tumour composed of spindle cells with ovoid to irregular nuclei with nuclear polymorphism (mitotic figures 10/10 hpf). Tumour cells were negative for S-100, CD -34, SMA and CD-117. The tumour was diagnosed as recurrent malignant spindle cell tumour with intra-abdominal and mediastinal extension. A gastrosurgery opinion was taken but the tumour was found to be inoperable in view of its mediastinal extension. Finally the patient was started on chemotherapy in form of MAID regimen (mesna, doxorubicin, ifosfamide, dacarbazine) and radiotherapy. Patient is currently doing well after receiving 4 cycles of monthly treatment with further plan of debulking surgery
Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF.Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes.Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH.Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.
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