Exploring autoantibodies as predictors of severe fibrosis or cirrhosis in metabolic dysfunction associated with steatotic liver disease.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns. Identifying predictive markers for advanced liver disease in MASLD patients is crucial for early intervention. This study investigates the association between autoantibody positivity and risk for severe fibrosis or cirrhosis across various subgroups. Methods: We conducted a retrospective study of adult patients diagnosed with MASLD between 1994 and 2019. Autoantibody status (anti-nuclear and anti-smooth muscle antibodies) was assessed using laboratory studies. Hepatic fibrosis or cirrhosis was determined histologically or through accepted non-invasive measures. Logistic regression analyses were employed to evaluate the association between autoantibody positivity and severe fibrosis or cirrhosis. Patients with comorbid viral and alcohol liver disease were assessed separately. Results: Among 2,749 MASLD patients, 1,425 (51.8%) were male and 1,324 (48.2%) were female, with a mean age of 58.7 years. A total of 541 (19.7%) patients tested positive for autoantibodies. Autoantibody positivity was associated with a higher risk of severe fibrosis or cirrhosis in MASLD patients (odds ratio 1.28, 95% CI [1.0-1.6]). This association persisted across various subgroups, including those with concurrent hepatitis B and C virus infections. In contrast, in alcohol liver disease, autoantibody-positive patients exhibited a lower risk. Conclusion: Autoantibody positivity emerges as a potential predictive marker for advanced liver disease in MASLD patients, facilitating risk stratification and tailored interventions. This study highlights the clinical relevance of autoantibodies in MASLD and underscores the need for prospective validation and mechanistic investigations to refine risk assessment and management strategies.

Identifying patients with diagnosed cirrhosis in administrative health databases: a validation study.

Objectives: Case ascertainment algorithms were developed and validated to identify people living with cirrhosis in administrative health data in Manitoba, Canada using primary care electronic medical records (EMR) to define the reference standards. Methods: We linked provincial administrative health data to primary care EMR data. The validation cohort included 116,675 Manitobans aged >18 years with at least one primary care visit between April 1998 and March 2015. Hospital records, physician billing claims, vital statistics, and prescription drug data were used to develop and test 93 case-finding algorithms. A validated case definition for primary care EMR data was the reference standard. We estimated sensitivity, specificity, positive and negative predictive values (PPV, NPV), Youden's index, area under the receiver operative curve, and their 95% confidence intervals (CIs). Results: A total of 116,675 people were in the validation cohort. The prevalence of cirrhosis was 1.4% (n = 1593). Algorithm sensitivity estimates ranged from 32.5% (95% CI 32.2-32.8) to 68.3% (95% CI 68.0-68.9) and PPV from 17.4% (95% CI 17.1-17.6) to 23.4% (95% CI 23.1-23.6). Specificity (95.5-98.2) and NPV (approximately 99%) were high for all algorithms. The algorithms had slightly higher sensitivity estimates among men compared with women, and individuals aged ≥45 years compared to those aged 18-44 years. Conclusion: Cirrhosis algorithms applied to administrative health data had moderate validity when a validated case definition for primary care EMRs was the reference standard. This study provides algorithms for identifying diagnosed cirrhosis cases for population-based research and surveillance studies.

Comparison of different definitions of metabolic syndrome and their associations with non-alcoholic fatty liver disease: a retrospective study.

Background: Metabolic syndrome (MetS) is considered an important risk factor for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to measure the prevalence of MetS based on six different MetS definitions and compare the performance of various definitions for identifying diabetes, hypertension, and dyslipidemia among NAFLD patients. Methods: The definitions compared were those developed by the World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), American Association of Clinical Endocrinologists (AACE), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), and Interim Joint Statement "harmonized" criteria. Receiver operator characteristic (ROC) curves were plotted for the six MetS definitions with NAFLD diagnosis. The diagnosis for NAFLD was established based on liver imaging or biopsy compatible with fatty liver disease. Results: A total of 500 NAFLD patients were analyzed. The mean age was 61.2 (SD 13.2) years, and BMI was 32.7 (SD 8.0) kg/m2. The most prevalent MetS component was dyslipidemia (83%), followed by hypertension (60%), obesity (61%), and diabetes (57%). The prevalence of MetS according to the WHO, NCEP/ATP-III, IDF, AACE, AHA/NHLBI, and harmonized criteria was 69%, 59%, 54%, 64%, 78%, and 79%, respectively. The highest area under the ROC curve for diabetes and hypertension was with the WHO definition (0.7405) and (0.8120), respectively. Conclusions: The prevalence of MetS in NAFLD patients varies according to the definitions of MetS employed. The modified WHO definition appeared to be most useful for the screening of MetS in NAFLD patients.

Development and validation of a case definition to estimate the prevalence and incidence of cirrhosis in pan-Canadian primary care databases.

Aims: To develop and validate case definitions to identify patients with cirrhosis and alcohol-related cirrhosis using primary care electronic medical records (EMRs) and to estimate cirrhosis prevalence and incidence in pan-Canadian primary care databases, between 2011 and 2019. Methods: A total of 689,301 adult patients were included with ≥1 visit to a primary care provider within the Canadian Primary Care Sentinel Study Network between January 1, 2017, and December 31, 2018. A subsample of 17,440 patients was used to validate the case definitions. Sensitivity, specificity, predictive values were calculated with their 95% CIs and then determined the population-level prevalence and incidence trends with the most accurate case definition. Results: The most accurate case definition included: ≥1 health condition, billing, or encounter diagnosis for International Classification of Diseases, Ninth Revision codes 571.2, 571.5, 789.59, or 571. Sensitivity (84.6; 95% CI 83.1%-86.%), specificity (99.3; 95% CI 99.1%-99.4%), positive predictive values (94.8; 95% CI 93.9%-95.7%), and negative predictive values (97.5; 95% CI 97.3%-97.7%). Application of this definition to the overall population resulted in a crude prevalence estimate of (0.46%; 95% CI 0.45%-0.48%). Annual incidence of patients with a clinical diagnosis of cirrhosis nearly doubled between 2011 (0.05%; 95% CI 0.04%-0.06%) and 2019 to (0.09%; 95% CI 0.08%-0.09%). Conclusions: The EMR-based case definition accurately captured patients diagnosed with cirrhosis in primary care. Future work to characterize patients with cirrhosis and their primary care experiences can support improvements in identification and management in primary care settings.

Insulin secretion in liver transplant recipients following conversion to a prolonged release tacrolimus formulation.

Background: Post liver transplant diabetes mellitus (PLTDM) occurs in 10-40% of liver transplant recipients and is associated with increased morbidity and mortality. An important cause of PLTDM is tacrolimus induced, concentration-dependent, inhibition of insulin secretion. Objective: To determine if a newly licenced formulation of tacrolimus (Envarsus-PA), which achieves peak tacrolimus concentrations 20-30% lower than other tacrolimus formulations has less of an inhibitory effect on insulin secretion. Methods: Homeostatic model assessment (HOMA) for insulin secretion (HOMA-S) values and c-peptide levels were determined in 19 adult liver transplant recipients while being maintained on immediate- or slow-release tacrolimus formulations and repeated a minimum of 30 days following conversion to Envarsus-PA. Results: Insulin secretion was unchanged following conversion to Envarsus-PA (HOMA-S pre-conversion: 154 ± 133 vs. 129 ± 75, post-conversion [p = 0.32], and c-peptide levels; 1059 ± 602 and 934 ± 463 respectively, p = 0.42). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels were also unchanged (FBG 5.7 ± 0.8 pre-conversion vs. 5.6 ± 0.7 post-conversion; p = 0.36 and HbA1c 4.9±1.2 pre-conversion versus 5.5±0.2 post-conversion, p = 0.34). Conclusions: Envarsus-PA had no significant effect on insulin secretion or glucose homeostasis beyond that associated with other tacrolimus formulations in adult liver transplant recipients.

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

OBJECTIVES: We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. MATERIALS AND METHODS: In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. RESULTS: Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. CONCLUSIONS: Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Clinicopathologic characteristics andoutcomes of hepatocellular carcinoma associated with chronic hepatitis B versus hepatitis C infection.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver malignancy and one of the most common cancers worldwide. Few studies in Saudi Arabia have compared the clinicopathologic characteristics of HCC caused by hepatitis B virus (HBV) versus hepatitis C virus (HCV) and their effect on patient survival and prognosis. OBJECTIVES: Identify differences in clinicopathological characteristics and outcomes of hepatocellular carcinoma (HCC) caused by HBV versus HCV. DESIGN: A retrospective medical records review. SETTING: Tertiary medical center in Riyadh. PATIENTS AND METHODS: We included all new cases of HCC with underlying HBV and HCV infection diagnosed between January 2013 and September 2017 that met inclusion criteria. MAIN OUTCOME MEASURES: Clinical, biochemical, pathological and radiological characteristics, and survival differences were compared between HCC that developed in HBV- and HCV-infected patients. SAMPLE SIZE: Of 253 patients evaluated, 172 patients were included in the study. RESULTS: Of the 172 patients, 110 (64%) had HCV-associated HCC and 62 (36%) had HBV-associated HCC. More patients with HBV infection were males (P=.003) and were younger (P=.015) than HCV patients. HCV-infected patients who developed HCC had more advanced cirrhosis (P=.048). The prevalence of comorbidities and pre-existing cir.rhosis was similar in both groups. Seven patients (6.8%) with underlying HCV developed HCC in the absence of cirrhosis. Patients with HBV-associated HCC were less likely to meet Milan criteria at initial diagnosis than those with HCV-associated HCC (33.9% vs. 52.7%, respectively, P=.017). HBV-associated HCC occurred at a more advanced Barcelona Clinic Liver Cancer stage. The overall median survival and treatment outcome for each modality was comparable. CONCLUSIONS: HBV- and HCV-associated HCC have distinct clinical and pathological characteristics, necessitating different screening policies to optimize HCC surveillance and management. However, viral etiology did not affect the treatment outcome and long-term survival. LIMITATIONS: Conducted in a single-center, retrospective and lacks information about the use of antiviral treatment. CONFLICT OF INTEREST: None.

Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

BACKGROUND: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. METHODS: One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. RESULTS: One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. CONCLUSIONS: Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.

Recurrence of autoimmune liver diseases after liver transplantation.

Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT.

Post-transplant lymphoproliferative disorder in liver recipients: Characteristics, management, and outcome from a single-centre experience with >1000 liver transplantations.

BACKGROUND: The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited. OBJECTIVES: To study the incidence, predictors and outcomes of PTLD after liver transplantation in a single, large-volume centre. METHODS: The charts of all LTRs (n=1372) in the authors' centre between January 2000 and June 2012 were retrospectively reviewed and those who developed PTLD were identified. Demographic, clinical and treatment data were prospectively collected. Responses to treatment, including complete response, no response, relapse and survival, were recorded. RESULTS: The incidence of PTLD in LTRs was 32 in 1372 (2.3%). Overall, median survival was 37 months (range 0.5 to 195 months), with one-, three- and five-year survival rates of 81%, 74% and 60%, respectively. Epstein-Barr virus (EBV)-negative patients had a better mean (± SD) survival (95±79 months) than EBV-positive patients (41±42 months) (P=0.02). For stage I/II PTLD, one-, three- and five-year actuarial survival was 87%, 87% and 75%, compared with 50%, 30% and 0% for stage III/IV PTLD, respectively (P=0.001). In patients with complete response, median survival was 58 months (range 10 to 195 months); and one-, three- and five-year actuarial survival was 100%, 94% and 76%, respectively, after diagnosis of PTLD. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival (seven of seven survivors) compared with only decreasing or stopping IS (14 of 25 survivors) (P=0.07). CONCLUSIONS: This series from a single large-volume centre showed excellent short and long-term survival after PTLD in adult LTRs who were EBV negative, had early disease and showed complete response. Consistent with the known in vitro antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival.

High sustained virological response to pegylated interferon and ribavirin for recurrent genotype 3 hepatitis C infection post-liver transplantation.

INTRODUCTION: Treatment outcomes of recurrent HCV genotype 3 (GT-3) after liver transplantation (LT) are ill-defined. AIMS: To determine efficacy, predictors, and long-term survival after treatment of recurrent HCV GT-3 infection, post-LT, with a combination of pegylated interferon (PEG) and ribavirin (RBV). METHODS: We studied all LT recipients (LTR) in our program treated with PEG and RBV for recurrent HCV GT-3 between Jan 1st 2002 and Dec 31st 2013. Antiviral therapy (AVT) was started if histology showed recurrent HCV with ≥ stage 2 fibrosis. Treatment was intended for 24 or 36 weeks, depending on early virologic response, and/or 24 weeks consolidation. Primary endpoint was sustained virological response (SVR). We also studied predictors of SVR and long-term patient survival. RESULTS: Among 492 LT for HCV-related cirrhosis and/or hepatocellular carcinoma performed during the study period, 110 (22%) had HCV GT-3 infection. Fifty-two (10.5%) HCV GT-3 patients had indications for AVT. Six were unable to complete the AVT, three because of clinical decompensation and one each because of metastatic disease involving the brain, lung cancer, and ductopenic rejection. Forty-seven (90%) patients achieved early virological response (EVR) and 37 (71%) achieved SVR. Predictors of SVR were EVR (p < 0.001), stage ≤ 3 fibrosis (p = 0.008), and 36 weeks treatment duration (p < 0.001). Less advanced fibrosis ≤ 3 was independent predictor of SVR (OR 0.18, 95% CI 0.05-0.67). SVR patients had actuarial (Kaplan-Meier) 1, 3, and 10 year post-treatment survival of 100, 100, and 95%, compared with 87, 78, and 20% for non-SVR patients (p < 0.001, log rank test). CONCLUSION: Efficacy of AVT for recurrent HCV GT-3 post-LT is high, and comparable with that for non-transplant patients. Less advanced fibrosis is an independent predictor of SVR. SVR improves long-term survival.

Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience.

INTRODUCTION: Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experience with triple therapy using protease inhibitors (PI) boceprevir (BOC), telaprevir (TVR) in these patients has been limited. MATERIAL AND METHODS: This national multicenter retrospective study included 76 patients (64 male, mean age 57 ± 6 years), treated for G1 HCV recurrence with either BOC (n = 41) or TVR (n = 35), who were non-responders or relapsers (n = 54), treatment naïve (n = 22) or had fibrosing cholestatic HCV (n = 3). 53 patients were on cyclosporine, 22 on tacrolimus and one patient on prednisone alone. RESULTS: On treatment virologic response was observed in 84% (64/76), 83% in BOC and 85% in TVR group. A higher week 4 response after starting triple therapy (RVR) was noted in TVR group 25/35 (81%) as compared to BOC group 26/41 (63%); p value = 0.02. The end of treatment response was 78% and 75% in BOC and TVR group, respectively. SVR 12 weeks after treatment discontinuation was observed in 59.5% (22/37); 58.3% in the BOC group and 61.5% in TVR group. Treatment was discontinued early in 23 patients (serious adverse effects n = 19, treatment failure n = 4). Infections occurred in 5 patients with 2 deaths (all in BOC). Anemia was the most common side effect (n = 55, 72%) requiring erythropoietin and RBV dose reduction. In the BOC group, cyclosporine dose reduction was 2.2 ± 1.0 fold and 8.6 ± 2.4 fold with tacrolimus. In TVR group, dose reduction was 3.0 ± 1.4 with cyclosporine and 12 ± 5.7 fold with tacrolimus. CONCLUSIONS: PI-based triple therapy appears more effective in producing HCV-RNA clearance than dual therapy. Tolerability is a serious issue and drug-drug interactions are manageable with close monitoring.

Midazolam for sedation during diagnostic or therapeutic upper gastrointestinal endoscopy in cirrhotic patients.

AIM: The objective of this study was to determine the frequency of clinically overt hepatic encephalopathy (HE) in cirrhotic patients undergoing diagnostic or therapeutic upper gastrointestinal endoscopy (UGE) who received midazolam for sedation. METHODS: This was an interventional study carried out at Liaquat National Hospital, Karachi. Consecutive patients presenting to the service of a single consultant gastroenterologist for diagnostic or therapeutic UGE between January 2009 and January 2011, who fulfilled the inclusion and exclusion criteria, were prospectively recruited for the study. The administration of intravenous midazolam was carried out in an incremental manner, whereas pulse and oxygen saturation was monitored during every procedure. During the recovery period, the degree of alertness was measured at 2, 4, and 6 h by the resident using the observer's assessment of alertness and sedation score and time to full recovery was determined. RESULTS: A total of 191 consecutive patients who underwent diagnostic or therapeutic UGE fulfilling the inclusion and exclusion criteria were recruited. The mean age was 51.30 ± 10.7 years, with an age range of 12-75 years. The majority of the patients were men (n=108, 56.5%), with 83 women (43.5%). A total of eight patients (4.2%) remained drowsy and developed clinically overt HE after the procedure on assessment at 2 and 4 h. However, all of these patients regained full consciousness at 6 h spontaneously. Among those eight patients who developed clinically overt HE, seven (87.5%) were Child-Pugh class C and one patient (12.5%) was Child-Pugh class B. Overt HE was significantly related to Child-Pugh class (P=0.005) and the dose of midazolam (P=0.02). CONCLUSION: We concluded that intravenous midazolam can be used safely in cirrhotic patients of Child-Pugh class A and B undergoing UGE for conscious sedation, but caution should be exercised for patients with advanced liver disease.

Familial adenomatous polyposis.

Familial adenomatous polyposis represents approximately 1% of all colorectal tumours and is caused by germline mutations in the adenomatous polyposis coli (APC) gene. A 38-year-old lady presented with abdominal pain, diarrhoea and iron deficiency anemia. There was no history of colorectal cancer in the family. Colonoscopy showed hundreds of polyps throughout the colon sparing the rectum, and an ulcerative tumour of the sigmoid colon. The diagnosis was familial adenomatous polyposis (FAP) and adenocarcinoma of the sigmoid colon. Colectomy with ileorectal anastomosis was performed and later on she was given chemotherapy and advice life long surveillance. The patient had one brother and one sister, without clinical symptoms. The brother had a single hyperplastic rectal polyp, while the sister refused colonoscopy. The patient has 2 sons, the elder son had normal colonoscopic findings, and the younger son was also diagnosed as a patient of FAP and referred for colectomy.

Appraisal of the knowledge of Internet users of Pakistan regarding hepatitis using on-line survey.

BACKGROUND: Hepatitis B and hepatitis C are global health care problems causing morbidity and mortality. Much of it could be prevented by better education of the masses regarding its spread. The study was conducted to assess the knowledge base of internet users of Pakistan to help in formulating education strategies. METHODS: A survey questionnaire consisting of 20 close ended questions was designed and hosted on a website. The responses submitted at the website were auto-emailed to the author. RESULTS: A total of 1024 complete responses were included. The survey shows increased level of awareness according to the educational status. The knowledge status of lowest education level was also adequate possibly due to access to internet to these respondents. CONCLUSION: Internet users in Pakistan have adequate core knowledge regarding hepatitis.

Comparison of heart rate and QTc duration in patients of cirrhosis of liver with non-cirrhotic controls.

OBJECTIVE: To compare QTc duration and Heart Rate (HR) in patients with cirrhosis with non-cirrhotic controls. DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Civil Hospital and Lyari General Hospital, Karachi, from March 2004 to February 2006. PATIENTS AND METHODS: Confirmed patients of cirrhosis were selected and allocated to Group-I. An equal number of non-cirrhotic patients were taken as control and were allocated to Group-II. ECG was recorded and values of HR and QTc were calculated. Comparison of increased frequency of HR and prolongation of QTc were done using Chi-square test or Fisher's Exact Test with significance level at

Idiopathic gastroparesis.

This case report describes a young female with idiopathic gastroparesis, who presented with persistent vomiting and weight loss. Treatment with erythromycin and tegaserod led to the recovery from symptoms and weight gain.

Correlation between clinical endoscopic and histological findings at esophago-gastric junction in patients of gastroesophageal reflux disease.

OBJECTIVE: To determine the correlation between the clinical, endoscopic and histological findings in patients of GERD. DESIGN: An observational, cross-sectional study. PLACE AND DURATION OF STUDY: Lyari General Hospital, Dow University of Health Sciences from November 2003 to October 2004. PATIENTS AND METHODS: Patients complaining of heartburn and/or acid regurgitation at least twice per week for at least 3 months were inducted in the study. Presence of clinical symptoms of epigastric pain, retrosternal burning, and reflux were recorded. Patients were subjected to esophagogastroduodenoscopy and four biopsies were taken from esophago-gastric junction. Correlation/regression analysis was done on clinical, endoscopic and histological findings. RESULTS: A total of 196 patients were selected and endoscopically examined. Most common grade given by patients to epigastic pain was grade-4 (42.9%), retrosternal burning as grade-4 (41.8%) and reflux grade-5 (36.7%). There was significant correlation between the clinical severity of epigastric pain with endoscopic findings (p = 0.002) and reflux (p = 0.0) but no correlation was observed with histological findings (p = 0.19). Out of 109 (55.6%) patients who had normal mucosa on endoscopy but on histology 70 (35.7%) of them had inflammation. Grading of endoscopic and histological findings showed significant correlation with each other (p = 0.0). CONCLUSION: Endoscopic negative GERD is common; severity of clinical symptoms does not correlate [corrected] with endoscopic findings while histopathological findings correlate with those of endoscopic findings [corrected]