Helicobacter pylori outer membrane protein Q genotypes and their susceptibility to anti-adhesive phytotherapeutic agents / 中西医结合学报

<p><b>OBJECTIVE</b>Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q (HopQ) mediates host-pathogen interactions; HopQ genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against HopQ genotypes and H. pylori cytotoxin-associated gene A (CagA).</p><p><b>METHODS</b>DNA was extracted by polymerase chain reaction of the HopQ genotypes (i.e., type 1, type 2 and CagA) from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.</p><p><b>RESULTS</b>C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against HopQ type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against HopQ type 2. C. longa (93%), C. annum (89%) and A. esculentus (75%) had better anti-adhesive activity against H. pylori with HopQ type 1 compared to HopQ type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum (14.7% ± 4.1%), A. esculentus (12.3% ± 4.1%) and Z. officinale (8.4% ± 2.8%) had an anti-adhesion effect against CagA-positive H. pylori strains compared to CagA-negative strains.</p><p><b>CONCLUSION</b>The anti-adhesion properties of the tested phytotherapeutic dietary ingredients were varied with HopQ genotypes. HopQ type 1 was found to be more sensitive to extracts of C. annum, C. longa and A. esculentus compared to the HopQ type 2 genotype.</p>

Clinicopathological study of seronegative celiac disease in adults in Pakistan: a pilot study

Background: celiac disease [CD] is usually missed, if the serology is negative. We aimed to evaluate the clinicopathological characteristics of seronegative CD [SNCD] and its response to gluten-free diet [GFD] in adult patients

Methods: this observational study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from 2009 to 2015. All consecutive adult patients [>/=17 years] with features of marked villous atrophy [Marsh class>/=III] on duodenal biopsy, negative tissue transglutaminase IgA and IgG antibodies [anti-tTg IgA and IgG] and human leukocyte antigen [HLA] DQ2 or DQ8 serotypes were studied. Clinical characteristics, laboratory parameters, and response to GFD were analyzed by SPSS software version 20. Median and interquartile range [IQR] were used for summarizing quantitative data. Frequency [percentages] was used for qualitative data

Results: a total of 12 patients with median age of 31.5 years [IQR: 19.75-46.75 years], of whom five [41.6%] were men were studied. The presenting complaints were: weight loss in 11 [91.6%] and abdominal pain in 9 [75%] patients. Anemia was observed in 10 [83.3%] patients with median hemoglobin of 9.5 g/dL [IQR: 6.3-13.25 g/dL]. Median alanine transaminase [ALT] was 21 U/L [IQR: 13-27 U/L] and median albumin was 3 g/dL [IQR: 2.4-3.6 g/dL]. Anti-tTg IgA and IgG were negative in all patients. HLA DQ serotyping showed homozygous DQ2 and DQ8 in four and one patients, respectively; while heterozygous DQ2 and DQ8 in five and two patients, respectively. All patients were advised to receive GFD. Nine [75%] patients showed complete clinical response. Two patients were non-compliant and one with non-alcoholic fatty liver disease [NAFLD]-related cirrhosis had partial clinical response. Out of the nine responders, two patients showed response within 6 months while the remaining showed improvement over a year period

Conclusion: the diagnosis of SNCD is rewarding as it responds favorably to GFD in most patients. HLA serology provides an important tool for diagnosis of this entity

Interferon lambda-3 rs12979860 variants and response to pegylated interferon in chronic hepatitis-c genotype-3

Objective: To assess the role of single nucleotide polymorphisms [SNPs] near the interferon lambda-3 [IFNX3] [formal IL-28B] gene rs12979860 in predicting sustained virologic response [SVR] in hepatitis-C virus genotype-3 [HCV-3]

Study Design: Descriptive, analytical study

Place and Duration of Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014

Methodology: Patients with HCV-3 were classified as sustained virologic response [SVR], relapsers and non-responders. SNP rs12979860 was determined by PCR-RFLP protocol. Differences between categorical variables were assessed by chi-square or Fisher's exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary logistic regression analysis by forward conditional method was performed by using significant variables with p-values less than 0.05 as the criteria for model inclusion

Results: Out of 115 patients, rs12979860 genotype-CC, CT, TT was found in 37 [32.2%], 70 [60.9%], and 8 [7%] patients. 72 patients were male with median age of 45 years. Cirrhosis was present in 32 patients. Patients with response failures [no response and relapse, n=36 and 29, respectively] had higher baseline gamma glutamyl transferase [GOT] level [p < 0.001], higher alanine aminotransferase [p=0.027] and cirrhosis [p=0.001] than patients with SVR. Genotype-CC was present in 16/65 in response failures compared to 21/50 who achieved SVR [p=0.048]. Rapid virologic response [RVR] [p < 0.001], low GGT [p=0.001] and absence of cirrhosis [p=0.039] were the independent predictive factors for SVR. In patients who could not achieve RVR and in patients with cirrhosis, SVR was seen more in with genotype-CC [p=0.007 and 0.038]

Conclusion: In patients infected with HCV-3, IFNA3 rs12979860, SNP has less impact on SVR

Coexistence of celiac and crohn's disease in a patient presenting with chronic diarrhea

Celiac disease [CD] is one of the most common causes of malabsorption. It is an immune-mediated disease manifested by diarrhea, steatorrhea, flatulence, and weight loss, caused by ingestion of gluten containing diets. The disease has typical small intestinal biopsy features of villous atrophy, crypt hyperplasia, and intense inflammation of the mucosal layer. The disease is rarely associated with Crohn's disease [CRD]. Studies on the impact of CD on the natural history of inflammatory bowel disease [IBD] have shown that the natural course of CRD is not influenced by coexistent CD. We report a case of 54-year female who presented with diarrhea and weight loss. On initial evaluation, CD was diagnosed, and responded to gluten-free diet [GFD]. Later on, she developed joint pains and her diarrhea recurred. Further evaluation revealed coexistence of CRD. The treatment of CRD was also initiated and this led to marked improvement in the symptoms of the patient

Ascites in patients on maintenance hemodialysis: causes, characteristics and predicting factors

Objective: To describe the causes, characteristics and factors associated with ascites in patients on maintenance hemodialysis

Study Design: Observational study

Place and Duration of Study: Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from November 2007 to November 2014

Methodology: All patients on maintenance hemodialysis and age > 16 years with ascites were included. Frequencies and percentages were computed for different categorical variables. Chi-square or Fischer exact test were used to identify factors associated with ascites like frequency of hemodialysis, serum albumin and cardiac ejection fraction [EF]. Odds ratios were calculated for associated factors

Results: Ninety patients were included in this study; 55.5% were males. Median age was 33 years. Cause of ascites was nephrogenic in 77.8%, cardiac failure in 16.7%, hypothyroidism in 6.67%, liver cirrhosis in 4.4%, abdominal tuberculosis in 2.2%, and peritoneal carcinomatosis in 1.1% patients. The ascites was severe in 53.3% patients and severity was associated with serum albumin < 2.8 gm/dL [p=0.007] and cardiac EF < 40% [p=0.028]. The ascites was low serum ascites albumin gradient [SAAG], high protein type [LSHP] in 60% patients and associated with hemorrhage [p=0.040]. High SAAG, high protein [HSHP] ascites, found in 33.3%, was associated with cardiac EF < 40% [p=0.005] and portal hypertension [p=0.048]. High SAAG, low protein [HSLP] ascites, seen in 6.7%, was associated with portal hypertension [p=0.006]

Conclusion: The commonest cause of ascites in hemodialysis dependent patients is nephrogenic followed by cardiac failure. Low serum albumin and low cardiac EF predispose to severe forms of ascites

Hypoglycemic and hypolipidemic effects of Lactobacillus fermentum, fruit extracts of Syzygium cumini and Momordica charantia on diabetes induced mice

A lot of treatment strategies available for diabetes but its complications are still a medical problem around the globe. It demands to find out some alternative therapeutic measures. In order to investigate the anti-diabetic potential of probiotics and natural extracts, this study was designed. Accordingly, a local source of yogurt probiotic strain Lactobacillus fermentum was isolated and characterized that showed its probiotic properties. Besides this, natural extracts of plants fruits like java plum [Syzygium cumini] and bitter gourd [M. charantia] were made. Lactobacillus fermentum and the extracts were administered individually as well as in combination to diabetes induced mice. Different parameters like body weight, blood glucose level and lipid profile including total cholesterol, HDL and LDL were analyzed before and after treatment. The results showed that Lactobacillus fermentum and natural extracts have hypoglycemic as well hypolipidemic activity against diabetic mice. This study can further investigated to screen potential compounds from these extracts to control the glucose and the lipid levels in diabetic patients

Hep-net opinion about the management of patients with chronic hepatitis C in Pakistan in the era of available direct acting antivirals

In Pakistan, we have 4.9% prevalence of HCV in general population, with 79% genotype 3. Recently Sofosbuvir has been made available at compassionate price in Pakistan. Management of chronic hepatitis C includes counseling of HCV patients, their proper assessment to select those who need antiviral therapy, initiation of appropriate antiviral agents and duration of therapy, along-with careful monitoring for safety and efficacy. Hepatic status as well as previous history of HCV therapy needs to be taken in the consideration before starting antiviral therapy. Other factors include co-morbid conditions like obesity, DM, NASH, etc. Treatment of special populations like liver transplant patients, patients with HBV co-infection, chronic kidney disease and hemoglobinopathies need special considerations when initiating HCV therapy

Clinical presentation and predictors of survival in patients with Budd Chiari syndrome: experience from a tertiary care hospital in Pakistan

To determine aetiology, clinical presentation and predictors of survival in Budd Chiari Syndrome patients. The prospective observational study based on non-probability convenient sampling was conducted at the Sindh Institute of Urology and Transplantation [SIUT], Karachi, and comprised Budd Chiari Syndrome patients between January 2004 and December 2013. The patients were evaluated for onset of symptoms, causes, mode of presentation and predictors of survival. SPSS 20 was used for statistical analysis. Of the 25 patients, 16[64%] were males, and 16[64%] belonged to the paediatric age group. Overall age range was 2-50 years with a mean of 14.7 +/- 12.41 years. Presentation was chronic in 14[56%] patients, acute in 10[40%] and acute on chronic in 1[4%]. Commonest morphological abnormality involved was hepatic veins alone in 14[56%]. Probable aetiologies were hypercoagulable states in 21[84%] patients, infections in 2[8%] and malignancy in 1[4%]. Among hypercoagulable states, protein C deficiency was the commonest, affecting 9[36%] patients. Seven [28%] patients died; acute 4[16%] and chronic 3[12%]. Causes of death included sepsis 4[16%], fulminant hepatic failure 1[4%], gastrointestinal bleeding 1[4%], and bleeding from liver biopsy site 1[4%]. Poor survival was associated with bilirubin >5mg/dl [p<0.031], serum alanine transaminase >40U/L [p<0.005], serum albumin <2.8 g/dl [p<0.008], Child-Turcotte-Pugh score >10 [p<0.001] and absence of varices [p<0.025]. Cox regression analysis failed to show any significant independent predictors of survival. Budd Chiari Syndrome affected young patients more frequently and was associated with high mortality. The commonest aetiology was hypercoagulable state. Survival was poor in patients with decompensated liver disease and those with an acute clinical presentation

Varied presentation of celiac disease in Pakistani adults

The objective of this retrospective study was to evaluate presentation of celiac disease in adults. It included 77 patients, 41 [53.2%] males with median age 26 years and median body mass index of 18 [16 - 22] kg/m[2]. Typical presentation with gastrointestinal symptoms was seen in 76.6%. Atypical presentation with extra intestinal complaints in 7.8% and silent presentation in 15.6%. Major symptoms were diarrhea in 64.9%, weight loss 36.4%, abdominal pain 35.1%, vomiting 32.5%, pallor 24.7%, and weakness 13%. Iron deficiency was documented in 20.8%, B12 deficiency in 9.1%, folic acid deficiency in 6.5% and vitamin D deficiency in 10.4%. Half of the patients had haemoglobin less than 11 g/dl. Osteoporosis and osteomalacia, hypothyroidism, diabetes and atrophic gastritis were seen in 2.6% each. Raised alanine aminotransferase was documented in 23.4%. Duodenal biopsy, done in 39 patients, revealed increased intraepithelial lymphocytes in 11, along with crypt hyperplasia in 3, partial villous atrophy in 15 and sub-total villous atrophy in 10. In conclusion, celiac disease in adults should be looked for in patients with chronic diarrhea or irritable bowel syndrome like symptoms, underweight, anaemic, or having nutritional deficiencies

Comparison of the virulence markers of helicobacter pylori and their associated diseases in patients from Pakistan and Afghanistan

Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E [cagA, cagE] and vacuolating-associated cytotoxin gene [vacA] alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied. Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. The cagA, cagE, and vacA allelic status was determined by polymerase chain reaction. The nonulcer dyspepsia [NUD] was common in the Afghan patients [P = 0.025]. In Afghan H. pylori strains, cagA was positive in 14 [82%] with gastric carcinoma [GC] compared with 29 [45%] with NUD [P = 0.006], whereas cagE was positive in 11 [65%] with GC and 4 [67%] with duodenal ulcer [DU] compared with 12 [18%] with NUD [P < 0.001 and 0.021, respectively]. The vacA s1a/b1was positive in 10 [59%] of GC compared with 20 [31%] in NUD [P = 0.033]. In Pakistani strains, cagE was positive in 12 [60%] with GC, 7 [58%] with GU, 12 [60%] with DU compared with 11 [16%] with NUD [P < 0.001, 0.004, and < 0.001, respectively]. In Pakistani strains, cagA/s1a/m1 was 39 [33%] compared with Afghans in 17 [19%] [P = 0.022]. Moderate to severe mucosal inflammation was present in 51 [43%] Pakistani patients compared with 26 [28%] [P = 0.033] in Afghans. It was also associated with grade 1 lymphoid aggregate development in Pakistani patients 67 [56%] compared with 36 [40%] [P = 0.016] in Afghans. Distribution of H. pylori virulence marker cagE with DU was similar in Afghan and Pakistan H. pylori strains. Chronic active inflammation was significantly associated with Pakistani H. pylori strains

Hepatocellular carcinoma in hepatitis D: does it differ from hepatitis B monoinfection?

Hepatitis D virus [HDV] superinfection in patients with chronic hepatitis B leads to accelerated liver injury, early cirrhosis, and decompensation. It may be speculated that hepatocellular carcinoma [HCC] may differ in these patients from hepatitis B virus [HBV] monoinfection. The aim of this study was to compare clinical aspects of hepatocellular carcinoma in patients of hepatitis D with HBV monoinfection. A total of 92 consecutive HCC cases seropositive for antibody against HDV antigen [HDV group] were compared with 92 HBsAg-positive and anti-HDV-negative cases [HBV group]. The features including sex, body mass index, presence of ascites, serum biochemistry, gross tumor appearance, child class, barcelona cancer liver clinic and okuda stages were not significantly different between the 2 groups. Decreased liver size was noticed more in cases of HDV compared with HBV group where the liver size was normal or increased [P=0.000]. HDV patients had lower platelets [P=0.053] and larger varices on endoscopy [P=0.004]. Multifocal tumors and elevated alpha-fetoprotein level>1000 IU/mL were more common in HBV group [P=0.040 and P=0.061]. TNM classification showed more stage III-IV disease in HBV group [P=0.000]. Decreased liver size and indirect evidence of more severe portal hypertension and earlier TNM stage compared with HBV monoinfection indicate that HDV infection causes HCC in a different way, possibly indirectly by inducing inflammation and cirrhosis

Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy

To evaluate the efficacy of L-ornithine-L-aspartate [LOLA] as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy [HE]. Randomized placebo controlled study. The Aga Khan University Hospital, Karachi in the year 2003-2004. Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A [NCT-A], ammonia level, clinical grade of HE and duration of hospitalization were assessed. Out of 120 patients, there were 62 males with mean age of 57 +/- 11 years. Improvement in HE was higher [n=40, 66.7%] in LOLA group as compared to the placebo group [n=28, 46.7%, p=0.027]. In patients with grade I or less encephalopathy, improvement was seen in 6 [35.3%] and 3 [20%] patients in LOLA and placebo groups respectively [p=0.667]. Patients with HE grade II and above showed improvement in 34 [79.1%] and 25 [55.6%] cases in LOLA and placebo group respectively [p=0.019]. On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 +/- 25.7 hours and 135.2 +/- 103.5 hours in LOLA and placebo groups respectively [p=0.025]. No side effects were observed in either groups. In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay

Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan

The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth [SIBO]. The aim of this study was to determine the frequency of SIBO and lactose intolerance [LI] occurrence in patients with diarrhea-predominant irritable bowel syndrome [IBS-D] according to Rome III criteria. In this retrospective case-control study, patients over 18 years of age with altered bowel habit, bloating, and patients who had lactose Hydrogen breath test [H2 BT] done were included. The "cases" were defined as patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea [CNSD] who did not fulfill Rome III criteria for IBS-D. Demographic data, predominant bowel habit pattern, concurrent use of medications, etc., were noted. Patients with IBS-D were 119 [51%] with a mean age of 35 +/- 13 years, while those with CNSD were 115 [49%] with mean age 36 +/- 15 years. Patients in both IBS-D and CNSD were comparable in gender, with male 87 [74%] and female 77 [64%]. SIBO was documented by lactose H2 BT in 32/234 [14%] cases. It was positive in 22/119 [19%] cases with IBS-D, while 10/115 [9%] cases had CNSD [P = 0.03]. LI was positive in 43/234 [18%] cases. Of these, 25/119 [21%] cases had IBS-D and 18/115 [16%] cases had CNSD [P = 0.29]. SIBO was seen in a significant number of our patients with IBS-D. There was no significant age or gender difference in patients with or without SIBO

Management of hepatitis B: Pakistan society for the study of liver diseases [PSSLD] practice guidelines

Pakistan remains in the intermediate prevalence area for Hepatitis B with an estimated carrier rate of 25%. Chronic Hepatitis B patients should be considered for treatment if Alanine transaminase [ALT] is persistently elevated in the last 6 months and HBV DNA is > 2000 IU/ml, irrespective of HBeAg status. In case of normal ALT and HBV DNA > 2000 IU/ml, treatment should only be considered if there is advanced fibrosis or cirrhosis on liver biopsy. HBV DNA positive cirrhotic patients should receive treatment irrespective of ALT status. Medicine available for the treatment of Hepatitis B in Pakistan are lamivudine, adefovir, telbivudine, entecavir, standard and pegylated interferon and thymosin. Patients who fail to achieve primary response as evidenced by < 2 log decrease in serum HBV DNA level after 6 months of nucleos [t] ide analogue therapy should have modification of treatment. Add-on adefovir therapy is indicated in those showing resistance to lamivudine or else switch to entecavir. For lamivudine-naive patients who develop drug resistance while on adefovir, add-on or switching to lamivudine, telbivudine or entecavir is indicated. Treatment should be stopped in HBeAg positive patients on oral antiviral agents who seroconvert [disappearance of HBeAg and appearance of anti-HBe antibody] with undetectable HBVDNA documented on two separate occasions at least 6 months apart. In HBeAg negative patients, discontinuation may be considered if undetectable HBV-DNA has been documented on three separate occasions 6 months apart although current evidence seems to support long term therapy in this group

Associations between the Plasticity Region Genes of Helicobacter pylori and Gastroduodenal Diseases in a High-Prevalence Area

BACKGROUND/AIMS: Genes associated with the Helicobacter pylori (H. pylori) plasticity region may play a role in the pathogenesis of H. pylori. We compared the genes jhp0940, jhp0947, and jhp0986 in H. pylori isolates from patients with different gastroduodenal diseases and in different age groups. METHODS: The H. pylori hyperplasticity region genes jhp0940, jhp0947, and jhp0986 were studied by PCR. We also evaluated whether these genes were related to the cytotoxin-associated gene (cagA) and histology findings. RESULTS: Of the patient cohort, 71 (62%) were positive for jhp0940, 67 (59%) for jhp0947, 12 (10%) for jhp0986, and 69 (60%) for cagA. jhp0940 (n=18, 67%) and jhp0947 (n=23, 85%) were found more frequently in duodenal ulcer (DU) patients than in gastritis patients (n=14, 39%; p=0.029 and p<0.001, respectively). Gastric ulcer (GU) was more frequently associated with jhp0940 (17 patients, 77%; p=0.003) than with gastritis (14 patients, 39%). Gastric carcinoma (GC) was more strongly associated with both jhp0940 (22 patients, 76%; p=0.003) and jhp0947 (22 patients, 76%; p=0.003) than was gastritis (14 patients, 39%). jhp0947 was more frequently associated with chronic active inflammation (58 patients, 87%; p=0.009) than with chronic inflammation (9 patients, 13%). Multivariate analysis demonstrated that jhp0947 was associated with DU (odds ratio, 6.1; 95% confidence interval, 1.87-20). CONCLUSIONS: The genes jhp0947 and jhp0940 were identified in H. pylori isolates from patients with GC and DU, while jhp0940 was also isolated from patients with GU. jhp0947 was independently associated with DU.