Anil John

Interleukin-28 and hepatitis C virus genotype-4: Treatment-induced clearance and liver fibrosis

AIM To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4. METHODS Two hundred and one HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment. Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up. Genotyping of IL28B rs12979860 was performed using the TaqMan assay. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI. RESULTS The study included 201 HCV-genotype 4 patients. The majority of patients were men (89.6%), with a median age of 47 years, inter-quartile range (40-51). Approximately 62.5% of patients had ETR, and 49.6% had SVR. Individuals who achieved SVR were more likely to be younger (χ(2) = 4.91, P = 0.027), and less likely to have fibrosis (χ(2) = 15.54, P < 0.0001), or inflammation (χ(2) = 7.58, P = 0.006). The genotype distribution of rs12979860 was 36.2%, 49.0% and 14.8% for genotypes CC, CT, and TT, respectively. In these participants, rs12979860 genotype distribution did not differ by gender (P = 0.466), pretreatment viral load (P = 0.600), inflammation (P = 0.435), or fibrosis (P = 0.291). The frequencies of IL28B rs12979860 genotypes were TT (14.8%), CT (49.0%), and CC (36.2%). Compared to rs12979860 genotype TT, aORs (95%CI) for ETR and SVR were: CC genotype, [17.55 (5.34-57.69) and 5.92 (2.09-16.76), respectively]; CT genotype, [5.15 (1.80-14.78) and 2.48 (0.94-6.52), respectively]. In the current study, the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%, respectively) than individuals who had ETR or SVR (47.9% and 47.2%, respectively). Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR = 5.92; 95%CI: 2.09-16.76). Similarly, patients with CT genotype had SVR more often than patients with TT genotype (aOR = 2.48; 95%CI: 0.94-6.52). Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR = 7.87; 95%CI: 2.84-21.82), and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR = 3.46; 95%CI: 1.37-8.74). In addition, data were consistent with a significant gene-dose relationship (aOR = 4.05/allele; 95%CI: 2.27-7.22). The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR. CONCLUSION In HCV-genotype 4 patients, rs12979860 is a sensitive predictor of viral clearance, independent of viral load, age, gender or fibrosis, with no similar relation to severity of fibrosis.

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

Background and Aim: Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. Materials and Methods: From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. Results: The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King’s score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King’s score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy. We derived the study score 8.5 − 0.2(albumin, g/dL) +0.01(AST, IU/L) −0.02(platelet count, 109/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. Conclusions: King’s score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Reexamination of the relationship between the prevalence of hepatitis C virus and parenteral antischistosomal therapy among Egyptians resident in Qatar

Egypt has the highest prevalence of recorded hepatitis C virus (HCV) worldwide, estimated nationally at 14.7%, which is attributed to extensive iatrogenic transmission during the era of parenteral antischistosomal therapy (PAT) mass-treatment campaigns. The objective of our study was to attempt to highlight to what extent HCV transmission is ongoing and discuss the possible risk factors. We studied the prevalence of HCV among 7.8% of Egyptians resident in Qatar in relation to age, socioeconomic status, and PAT and discuss the possible risk factors. HCV testing was conducted in 2,335 participants, and results were positive for 13.5%, and 8.5% for those aged below 35 years. The prevalence of HCV in the PAT-positive population was 23.7% (123 of 518, 95% confidence interval [CI] 20.2%–27.6%) compared with 11.2% in the PAT-negative group. Significantly higher HCV prevalence occurred in participants who were older than 50 years (23%, 95% CI 19.3%–27.1%) compared to those aged 45–50 years (19.3%, 95% CI 15.2%–23.8%), 35–45 years (11.1%, 95% CI 8.9%–13.7%), and less than 35 years (8.5%, 95% CI 6.8%–10.4%) (P<0.0001). Insignificant higher prevalence occurred in the low socioeconomic group (14.2%, 95% CI 11.3%–17.4%). Logistic regression analysis revealed that increasing age, history of PAT, bilharziasis, and praziquantel were common risk factors, but there was no relation with dental care. Host genetic predisposition seems to be a plausible underlying factor for susceptibility among Egyptians and intense ongoing infection.

Clinical Application of AIMS65 Scores to Predict Outcomes in Patients with Upper Gastrointestinal Hemorrhage

Background/Aims To evaluate the ability of the recently proposed albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65) score to predict mortality in patients with acute upper gastrointestinal bleeding (UGIB). Methods AIMS65 scores were calculated in 251 consecutive patients presenting with acute UGIB by allotting 1 point each for albumin level <30 g/L, INR >1.5, alteration in mental status, systolic blood pressure ≤90 mm Hg, and age ≥65 years. Risk stratification was done during the initial 12 hours of hospital admission. Results Intensive care unit (ICU) admission, endoscopic therapy, or surgery were required in 51 patients (20.3%), 64 (25.5%), and 12 (4.8%), respectively. The predictive accuracy of AIMS65 scores ≥2 was high for blood transfusion (area under the receiver operator characteristic curve [AUROC], 0.59), ICU admission (AUROC, 0.61), and mortality (AUROC, 0.74). The overall mortality was 10.3% (n=26), and was 3%, 7.8%, 20%, 36%, and 40% for AIMS65 scores of 0, 1, 2, 3, and 4, respectively; these values were significantly higher in those with scores ≥2 (30.9%) than in those with scores <2 (4.5%, p<0.001). Conclusions AIMS65 is a simple, accurate, non-endoscopic risk score that can be applied early (within 12 hours of hospital admission) in patients with acute UGIB. AIMS65 scores ≥2 predict high in-hospital mortality.

High Dose of Lamivudine and Resistance in Patients with Chronic Hepatitis B

Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B.

Hepatobiliary and Pancreatic: Triad of recurrent acute pancreatitis, duodenal web and intra-pancreatic duodenal duplication cyst: a new constellation?

A 31-year-old lady presented with four episodes of acute pancreatitis (AP) over the last 2 years. She had mild AP during each of these episodes and was managed symptomatically in a peripheral hospital. All the baseline investigations for the etiological work up for recurrent AP (liver function tests, lipid profile, serum calcium, endocrine profile, computed tomography scan) were normal. In our centre, upper gastrointestinal endoscopy showed a nonobstructing duodenal web, distally in the 2 part of duodenum. Endoscopic ultrasound (EUS) revealed an anechoic cystic lesion in the head of pancreas abutting the duodenal wall, measuring 1.5 cm with a hypoechoic “mural nodule” inside it (Fig. 1). During ERCP, just below the opening of common channel in the major papilla, there was a separate opening leading to the cyst in the pancreatic head (Fig. 2). Intra-cystic biopsy from the cyst wall showed features suggestive of duodenal duplication cyst (DDC). This represents a rare constellation of duodenal web, intrapancreatic DDC and recurrent AP. The apparent “pseudo mural nodule” in EUS was inspissated food and sludge. DDC is a rare congenital anomaly that occasionally causes recurrent AP. AP develops due to obstruction of the major papilla by the DDC and the migration of biliary sludge or secretions from the DDC to the biliopancreatic system. Clinical signs of gastrointestinal duplication cysts are nonspecific (abdominal pain, distention, bleeding, intussusception and pancreatitis) and related to the location and size of the cysts. Surgical intervention with complete resection is the treatment of choice. In lesions close to major papilla, partial resection with drainage or endoscopic incisions with marsupialisation have been reported.

Tu1059 Decompensation, Hepatocellular Carcinoma, Liver Related Hospital Admission and Liver Related Mortality After Antiviral Treatment: How Wiser Are We at the End of the Era of Conventional Dual Antiviral Therapy for Chronic Hepatitis C?

Background and aims: The CDC estimates that 75% of the U.S. CHC population is between 50 and 70 years of age. As this population ages, the increasing rates of significant comorbidities including end stage liver disease will make CHC management more challenging. Drug-drug interactions from medications used to treat these comorbidities may also contraindicate or complicate the use of cytochrome P-450 metabolized protease inhibitors commonly used in anti-HCV regimens. The purpose of this study is to measure the rates of comorbidities and medications that may create barriers towards initiating anti-HCV regimens in a large U.S. CHC cohort. Methods: This was a retrospective database study of a large U.S. cohort of insured patients with CHC from 1/1/2009 to 6/30/2014. Patients with CHC were identified through ICD-9 coding. A total of 80,112 patients were analyzed: 76,115 with commercial and 3,997 with Medicaid insurance. Results: Two-thirds (66%) of our CHC population were aged between 50 and 70 years, 61% were male, and 11% were women of child-bearing age. Nearly 70% of patients had at least one significant comorbidity such as hypertension (49%), diabetes (22%), coronary artery disease (1.8%), HIV (4%), asthma or COPD (16%), chronic kidney disease (2%), and depression (14%). In addition, nearly one-third of patients (30%) had evidence for end stage liver disease with ascites, hepatic encephalopathy, or esophageal varices. Across the entire study period, the median number of first-time filled prescriptions for any medication per year was 3.5 (IQR, 1 to 8). Patients with comorbidities had a significantly higher median number of first-time filled prescriptions per year as compared to those without comorbidities (median 5 (IQR, 2 to 11) prescriptions per year with comorbidities versus median 1.5 (IQR, 0.5 to 3.5) prescriptions per year without comorbidities. Most commonly prescribed P-450 metabolized medications were HMG-CoA reductase inhibitors (13%), anxiolytics (18%), antibiotics (21%), and calcium channel blockers (14%). In addition, there were significantly more prescriptions for P-450 metabolized medications in patients with comorbidities (67%) compared to those without comorbidities (41%) (Figure 1). Conclusions: In this analysis of a large U.S. cohort of CHC patients, the majority (70%) of patients had at least one comorbid diagnosis of hypertension, diabetes, coronary artery disease, COPD, chronic kidney disease, or depression. In this population, approximately 67% also had at least one prescription for a P-450 metabolized medication that may pose significant drug-drug interactions with some of the anti-HCV protease inhibitors. Therefore, there may be significant barriers to treatments with current and upcoming antiHCV regimens in a significant proportion of patients with CHC.

Therapeutic biliary and pancreatic endoscopy in Qatar- a five year retrospective audit

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an advanced endoscopic procedure in which a specialized side viewing duodenoscope is passed into the duodenum, allowing accessories to be pushed via biliary or pancreatic ducts for diagnostic and therapeutic intervention. It is one of the most complex endoscopic procedures, requiring specialized equipment and proficient and skilled operators and assistants. Today therapeutic ERCP is the intervention of choice for many pancreaticobiliary disorders. The Division of Gastroenterology & Endoscopy under the Department of Medicine has been performing ERCPs since the inception of the Endoscopy Unit in Hamad Medical Corporation (HMC), and it is the only endoscopy unit in Qatar performing ERCPs. We performed a retrospective audit of ERCPs performed over the last 5 year period from January 2006 to December 2010 in our Endoscopy unit.

233 Early Detection of Hepatitis C Using a One Minute Visual Qualitative Based Kit System in a Community Based Setting in Doha, Qatar

BACKGROUND: Early detection and treatment of Hepatitis C can change the natural history of disease. AIM: The primary aim of this study was to detect infection of hepatitis C using a rapid immunochromatographic assay in a community setting. The secondary aims included assessment of prevalence rate and disease characteristics; including liver function tests, viral load, grade and stage of disease on the liver biopsy. METHODS: Two cohorts of 4000 and 3212 people (.004% of the population) were surveyed over a three week period each between December 2008 through August 2009. Qualitative detection of hepatitis C antibodies was done using a colloidal gold enhanced rapid immunochromatographic assay (Health Chem Diagnostics LLC, FL-USA).Viral load was calculated using RT PCR (Taqman) and those found positive underwent liver biopsy.28 and 33patients with proven chronic hepatitis C formed the controls for validation of the kit used in the first and the second cohort. RESULTS: 64 people were detected to have positive antibodies (0.008%) to hepatitis C (Cohort 1 -33/ 4000, Cohort 231/3212). In the first cohort, among 28 persons with positive antibodies detected with the kit, abnormal LFT were observed in 21 (75 %) and 10 (35.7 %) had more than > 2 ALT levels (Range 17174 IU/ml).24 agreed for further testing with RT PCR and another 4 agreed for testing using another method (Enzyme immunoassay).The mean viral load was 5757445 IU/ml (Range 2756345448680 IU/ml).Only one person detected to have positive antibodies with the kit was found to have negative HCV PCR. 15 patients (62.5%) who underwent liver biopsy, 9 showed evidence of advanced fibrosis (≥F2) and 7 showed moderate necroinflammation (A 2). 12 patients (50%) undertook standard treatment with Pegylated Interferon and Ribavarin and 8 of them have achieved either rapid or early virological response at the last follow up. The prevalence rate was detected to be 15 per thousand people. The second cohort is under evaluation for further assessment and management. CONCLUSION: The kit test based detection technique for hepatitis C is quite an effective strategy for early detection especially in community based setting. Further large surveillance studies are required to detect this disease for its effective control.