Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

QSAR analysis of indazole estrogens as selective beta-estrogen receptor ligands: rationalization of physicochemical properties.

Quantification of structure activity relationships was performed on a series of indazole estrogen analogs, for their relative beta estrogenic receptor agonist activity, in order to understand the essential structural requirements for selectivity of indazole estrogen analogs for beta-estrogenic receptor over alpha-estrogenic receptor. The de novo and Hansch approach suggested that the 3(rd) position of indazole nucleus (R(1)) is decisive for the selectivity of molecules towards beta-estrogenic receptor over alpha-estrogenic receptor. The study also depicted that the substitution of polar group at R(1) position might prove helpful in the beta-estrogenic receptor selectivity (ER(beta/alpha )).

Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of occurrence and clinical importance.

BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC), results from anatomical obstruction or motor abnormalities. We studied patients with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one patients with GBC without endoscopic gastric outlet obstruction and 10 healthy controls were evaluated using a symptom scoring system for gastric stasis, saline load test and water perfusion antroduodenal manometry. Fasting, post-prandial and post-octreotide motility were recorded and analysed on a computer using GiPC manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17] v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460 ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without vomiting. Healthy subjects more often had spontaneous fasting migratory motor complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of contractions in the antrum and duodenum were significantly lower in patients with GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284] v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395], p<0.0001) antral motor indices than healthy subjects. Patients with GBC and vomiting had significantly lower contraction amplitude and motility indices than those without vomiting. Motility indices correlated inversely with the symptom score and volume of aspirate on the saline load test (Spearman correlation, p = 0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in patients with GBC. These may explain the symptoms of gastric stasis and abnormal results of the saline load test in the absence of anatomical obstruction in such patients.

Percutaneous Direct Needle Puncture and Transcatheter N-butyl Cyanoacrylate Injection Techniques for the Embolization of Pseudoaneurysms and Aneurysms of Arteries Supplying the Hepato-pancreato-biliary System and Gastrointestinal Tract.

AIMS: The aim of this study was to evaluate the safety and clinical efficacy of percutaneous direct needle puncture and transcatheter N-butyl cyanoacrylate (NBCA) injection techniques for the embolization of pseudoaneurysms and aneurysms of arteries supplying the hepato-pancreato-biliary (HPB) system and gastrointestinal (GI) tract. SUBJECTS AND METHODS: A hospital-based cross-sectional retrospective study was conducted, where the study group comprised 11 patients with pseudoaneurysms/aneurysms of arteries supplying the HPB system and GI tract presenting to a tertiary care center from January 2015 to June 2016. Four patients (36.4%) underwent percutaneous direct needle puncture of pseudoaneurysms with NBCA injection, 3 patients (27.3%) underwent transcatheter embolization with NBCA as sole embolic agent, and in 4 patients (36.4%), transcatheter NBCA injection was done along with coil embolization. RESULTS: This retrospective study comprised 11 patients (8 males and 3 females) with mean age of 35.8 years ± 1.6 (standard deviation [SD]). The mean volume of NBCA: ethiodized oil (lipiodol) mixture injected by percutaneous direct needle puncture was 0.62 ml ± 0.25 (SD) (range = 0.5-1 ml), and by transcatheter injection, it was 0.62 ml ± 0.37 (SD) (range = 0.3-1.4 ml). Embolization with NBCA was technically and clinically successful in all patients (100%). No recurrence of bleeding or recurrence of pseudoaneurysm/aneurysm was noted in our study. CONCLUSIONS: Percutaneous direct needle puncture of visceral artery pseudoaneurysms and NBCA glue injection and transcatheter NBCA injection for embolization of visceral artery pseudoaneurysms and aneurysms are cost-effective techniques that can be used when coil embolization is not feasible or has failed.

Effect of specific production rate of recombinant protein on multimerization of plasmid vector and gene expression level.

In fed-batch cultures of recombinant Escherichia coli BL21(DE3)[pT7-G3IL2] at high cell concentration, the post-induction specific growth rate was carefully regulated by controlled medium feed to maximize the synthesis level of recombinant fusion interleukin-2, G3.IL-2. A maximum concentration of G3.IL-2 (11.25 g l(-1)) was achieved in the induced recombinant culture growing at the rate of 0.056 h(-1). A steep decrease in the expression level of G3.IL-2 was observed at the post-induction specific growth rates higher than its optimal value (0.056 h(-1)). In the induced recombinant cultures, plasmid multimerization was observed and highly dependent on specific growth and production rate: a higher post-induction specific growth rate and an increased specific production rate tended to significantly promote it much further. Moreover, plasmid stability was found to decrease rapidly in a faster growing culture.

Secretory production of Arthrobacter levan fructotransferase from recombinant Escherichia coli.

Levan fructotransferase (LFTase) from Arthrobacter ureafaciens K2032 was expressed with N-terminal fusion of a LacZ-derived secretion motif (TMITNSSSVP) using the lac promoter system in recombinant Escherichia coli JM109 [pUDF-A81]. In flask cultures, recombinant enzyme activity was detected in culture media, and sequence analysis of N-terminal residues showed that about 40% of the extracellular recombinant LFTase had an authentic N-terminus. In a fed-batch bioreactor containing recombinant E. coli at high cell concentrations (OD(600)>200), the extracellular LFTase accumulated to 46000 U ml(-1) (approximately 2.0 g l(-1)) which was almost 40% of total (intra- and extracellular) recombinant LFTase. The synthesized recombinant enzyme was secreted soon after gene expression was induced by IPTG. Prolonged high secretion caused cell lysis and growth inhibition during the production phase in fed-batch cultures. When lactose was added by continuous feed mode, the secretion of recombinant LFTase and hence the cell lysis were significantly delayed in spite of the increased synthesis level. Therefore the induced cell culture of recombinant E. coli could grow up to a much higher cell concentration with continuing recombinant enzyme synthesis. In the case of the controlled feed of lactose, the maximum activities (U ml(-1)) of total and extracellular LFTase were nearly 100% and 70% higher, respectively.

Synthesis and anticonvulsant and neurotoxicity evaluation of N4-phthalimido phenyl (thio) semicarbazides.

The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.

Gastrointestinal endoscopy training in India.

A structured endoscopy training program with clear goals for proper teaching and evaluation serves to alleviate apprehensions in the minds of trainees regarding this crucial area. It also ensures that training is acquired not in isolation but in the setting of ongoing patient care, so that the emphasis is on how the procedure fits into the overall management plan for the patient. By specifying the details of the endoscopy unit set-up, the qualifications of the trainer and the number of procedures to be performed by the trainee, it is hoped that uniformity will be produced in the quality of training imparted, whether it be in a teaching or a non-teaching hospital. The end-product of such training, through the DM/MCh or the DNB stream, is a gastroenterologist who is also a certified endoscopist, capable of performing all standard diagnostic and therapeutic procedures. A further period of focused training for 1 to 2 years is required to achieve the level of competence expected of an advanced therapeutic endoscopist. There is little room for short-term training courses in endoscopy for the basic training of an endoscopist, although such courses are useful as CME activities, for the maintenance and renewal of skills of the trained endoscopist, as well as providing him with exposure to new and evolving therapeutic techniques. Efforts at improving and standardizing the training and practice of GI endoscopy in India are likely to remain exercises in futility without the active and dynamic involvement of all the leading professional societies in the country. The need of the hour is the establishment of technical committees for laying down standards in training and practice of GI endoscopy that should be voluntarily approved by all these societies so that they may then be implemented by the State medical councils and the MCI. A move in this direction from within the profession is far more appropriate and is also likely to find greater acceptance than such moves imposed from above, at the behest of judicial authorities. A system of hospital accreditation committees for large public and private sector hospitals offering endoscopy services, supervised by the accreditation committee of the State medical council, needs to be established. Clinics and nursing homes offering these services also need to be approved by the same committee after meeting standards similar to those laid down for larger hospitals. Mechanisms for audits of performance and outcome of endoscopic procedures as well as periodic participation in CME activities for maintenance of skills and expertise need to be established and linked to periodic renewal of credentials for practising GI endoscopy. Procedures for credentialing for new endoscopic techniques need to be established. The path ahead is long and arduous but we must tread it for it will only become more difficult if we procrastinate.

Duodenoscopic sphincterotomy for common bile duct stones in patients with gallbladder in situ.

Duodenoscopic sphincterotomy (DS) is a well established treatment for common bile duct (CBD) stones in post-cholecystectomy patients, but not in patients with gallbladder in situ. The main argument against the procedure in the latter set of patients has been that by performing it, one is leaving behind the diseased gallbladder which may require further treatment. We have, however, performed 60 DS in 49 patients with gallbladder in situ. The clinical picture of these patients was characterized by abdominal pain in 79.6%, jaundice in 91.8%, history of cholangitis in 46.9%, severe acute cholangitis at the time of DS in 28.6% and a major associated illness in 10.2% of them. Adequate sphincterotomy was performed in 91.8% of the patients with successful stone extractions in 93.3% and an overall CBD clearance in 85.7%. One patient (2%) with severe acute cholangitis, who had presented in a moribund state, died despite adequate DS. Three patients (6%) experienced an exacerbation of acute cholangitis after DS, two of them requiring emergency surgery. During subsequent follow-up, elective cholecystectomy was performed in 26 (54%) patients. Five additional patients are awaiting surgery. Seventeen (36%) patients continue to have their gallbladders in situ and over a mean follow-up period of 12.8 months (range, 4-32 mos) they have remained asymptomatic except for brief episodes of biliary pain in 2 patients. It is concluded that DS relieves the symptoms of CBD stones even in patients with gallbladders in situ and may suffice for patients who are frail, elderly and who have major associated illnesses.

Symptomatic chronic calcific pancreatitis in a patient with idiopathic ulcerative colitis and sclerosing cholangitis.

Although sclerosing cholangitis is well recognized to occur in patients with idiopathic inflammatory bowel disease, pancreatitis as a complication of ulcerative colitis is uncommon. We describe a patient who had idiopathic ulcerative colitis, primary sclerosing cholangitis and calcific pancreatitis with endocrine pancreatic deficiency, a rare combination.

Duodenoscopic sphincterotomy in a northern Indian hospital.

In a 36-month period, 154 duodenoscopic sphincterotomies (DS) were performed on 120 patients in a Northern Indian hospital. The major indication for DS was choledocholithiasis (95.8%), the rest being done for indications like papillary stenosis, periampullary carcinoma and the sump syndrome. Seven patients (5.8%) had significant associated medical illnesses. An adequate sphincterotomy was achieved in 91.6% of patients, with successful stone extraction in 95.3% of them. Overall clearance of the common bile duct (CBD) was thus achieved in 87.5% of the patients subjected to DS. Two patients (1.7%) died after undergoing DS, and six (5%) experienced early complications that necessitated emergency operation in two of them (1.7%). DS appears to be the treatment of choice for the management of choledocholithiasis in the postcholecystectomy patient as well as in the patient with gallbladder in situ who has cholangitis or jaundice or associated medical illness that may constitute a high risk for surgery.

Minimal hepatic encephalopathy: natural history, impact on daily functioning, and role of treatment.

Cirrhosis of liver is often complicated by minimal hepatic encephalopathy (mHE), which is detected by neuropsychiatric and neurophysiological tests. mHE develops more commonly in cirrhotics with severe liver disease and in those with esophageal and gastric varices. On follow up, these patients more often develop overt encephalopathy as compared to cirrhotics without mHE. mHE may affect daily activities like sleep, driving ability, alertness, social interaction, and communication. It is probably also an independent predictor of survival. The most practical treatment strategy for mHE has not been established; however, it can be treated as effectively as overt encephalopathy with similar agents. Treatment improves mHE in terms of psychometric tests, but improvement in daily functioning has not been well documented.

Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver.

INTRODUCTION: Gastric Helicobacter pylori infection is believed to be associated with a higher risk of hepatic encephalopathy among patients with cirrhosis of liver. However, the role of this infection in causation of subclinical hepatic encephalopathy has not been studied in detail. METHODS: Patients with cirrhosis of liver but no hepatic encephalopathy underwent venous blood ammonia measurement, psychometric tests (number connection tests [NCT] and figure connection tests [FCT]), and gastric biopsies for presence of H. pylori infection. The results of blood ammonia and psychometric tests in the H. pylori-positive and -negative study subjects were compared. RESULTS: Of 58 patients with liver cirrhosis studied, 31 had evidence of gastric H. pylori infection. Venous blood ammonia levels were comparable in patients with (median 29 mmol/L; range 18-47) and without (34 [15-48] mmol/L; p=ns) H. pylori infection. The time taken to complete NCT trail A (median 37 s [range 25-69] versus 36.5 [26-62]), NCT trail B (64 s [48-91] versus 63.5 [42-88]), FCT trail A (59 s [31-115] versus 58 [38-590]) and FCT trail B (76 s [55-187] versus 82 [36-125]) were similar in those with and those without H. pylori infection. For each of the four tests, the proportion of subjects with abnormal test results was similar among H. pylori-positive and -negative subjects. CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function.

Extra corporeal shock wave lithotripsy of bile duct stones: absence of short term complications with the use of very high number of shock waves.

Extracorporeal shock wave lithotripsy (ESWL), generated by the Siemens lithotripter (Lithostar), was used in six patients (two males, four females, aged 28 to 70 years) with large bile duct stones (diameter 16 mm to 30 mm; single in five, multiple in one) in whom routine endoscopic measures had failed. Disintegration of stones was achieved in four patients. The mean number of shocks delivered per patient, at energy levels generated by 19 kv, was 18,267 (range 4200-39,000) over 1 to 8 sessions, with a maximum of 6000 shocks per session. Exacerbation of cholangitis occurred in one patient after stone disintegration. Cutaneous petechiae were noted in four patients. Our report describes the use of a very high number of shock waves in the treatment of bile duct stones, with no appreciable short term complications noted in this small experience. Our initial experience of treating large bile duct stones with ESWL appears encouraging and safe.

Frequency, microbial spectrum and outcome of spontaneous bacterial peritonitis in north India.

AIM: To determine the prevalence, microbial spectrum and outcome of spontaneous bacterial peritonitis (SBP) and its variants in hospitalized cirrhotics. STUDY DESIGN: Prospective cohort study at a tertiary referral center in North India. METHODS: Over a four-month period, 70 consecutive adult patients with decompensated cirrhosis were screened for the presence of SBP or its variants. Ascitic fluid culture was done by direct inoculation of blood culture bottles at the bedside. Blood, urine and other fluids were cultured during hospital stay when clinically indicated. Ascitic fluid total leukocyte count and culture were repeated at any time during hospital stay if the patient showed clinical signs of deterioration. Patients with SBP and culture-negative neutrocytic ascites (CNNA) were treated empirically on the basis of ascitic fluid leukocyte count. RESULTS: Twenty-one of 70 (30%) patients with cirrhosis were diagnosed to have SBP or its variants CNNA and monomicrobial bacterascites (MBA). Ninety-five percent of the patients who developed this complication were in Child-Pugh class C. A causative organism was isolated in 62% of these patients. Gram-negative bucilli accounted for 6 of 10 patients with SBP whereas all cases of MBA were due to infection with Gram-positive cocei. A third of patients with SBP/CNNA had evidence of extra-abdominal focus of infection with the same organism. All episodes of SBP/CNNA were initially treated with either ciprofloxacin (12 patients) or a combination of third generation cephalosporin, cefotaxime and an aminoglycoside, gentamicin (n = 6). Fourteen patients (67%) recovered whereas 6 patients died during hospital stay. CONCLUSION: SBP is a common complication of decompensated liver disease in North India and is associated with significant in-hospital mortality. Ciprofloxacin is an effective drug for initial treatment of SBP/CNNA. Synchronous extra-peritoneal focus of infection is a frequent occurrence in these patients.

Membranous glomerulonephritis in association with ulcerative colitis.

Glomerulonephritis is a rare association of ulcerative colitis. We report a patient with ulcerative colitis who developed proteinuria due to membranous glomerulonephritis which responded to colectomy.

Young age carcinoma stomach with spontaneous bacterial peritonitis.

A case of disseminated carcinoma stomach at the age of thirteen years is reported. The patient in addition had spontaneous bacterial peritonitis.

Rapid reversal of manifestations of acquired zinc deficiency in alcoholic cirrhosis with diet therapy.

Features of acquired zinc deficiency syndrome occurred in an alcoholic cirrhotic during hospital stay while he was on parenteral nutrition. Rapid reversal of symptoms occurred with resumption of normal diet without additional zinc supplementation.

Primary biliary cirrhosis without pruritus--an Indian variant.

Primary biliary cirrhosis (PBC) is extremely rare in India. We report three cases of PBC without pruritus. The absence of pruritus in the present cases and in those reported earlier from India is highlighted.