Professor Gill's team has presented five research papers in 24th Asia Pacific association for study of liver diseases (APASL) meeting held in Istanbul Turkey from March 12th to March 15th.

Outcomes Of Therapeutic Response To Tenofovir Dipivoxil Fumarate (TDF) In Chronic Hepatitis B Pregnant Patients Muzzaffar Gill*, Sidra Gill, Ammara Nawaz, Misbah Malik, Faiza Irfan Gastroenterology Division, Maroof International Hospital, Islamabad, Pakistan Background and Aims: Antiviral therapy may be required during pregnancy to control maternal disease and to prevent vertical transmission at third trimester. We prospectively studied the efficacy and safety of TDF in managing these patients Methods: Chronic Hepatitis B mothers who required antiviral treatment during pregnancy were screened. Those with ALT 50 and above and HBV DNA more than 10,000 IU were treated with TDF until 52 weeks postpartum. Primary endpoints were HBV DNA < 5log10 copies/ml at delivery and the percentage of patients with HBV DNA undetectable at postpartum week 52. Secondary endpoints were safety, tolerability, serological and biochemical responses. Results: During 3/2012-3/2013, 30 consecutive chronic hepatitis B mothers were enrolled. All subjects received TDF 300 mg daily with mean (range) duration of 17.1 (9-39) weeks prior to delivery. At delivery, a significant reduction of HBV DNA was observed when compared to those at the baseline (2.8 vs. 7.1 log10 copies/mL, p<0.001), all mothers achieved HBV DNA reduction to the levels below 5log10 copies/ml. The treatment was well tolerated with no viral breakthrough. At postpartum week 4, four patients self-discontinued TDF without severe ALT flares. At postpartum week 52, 57% of mothers had undetectable HBV DNA levels. In addition, 7.1% percent of patients (1/14) had HBeAg loss/seroconversion; 64.3% of patients (9/14) achieved normalization of alanine aminotransferase; no patients had HBsAg loss. The adverse events were mild in severity grade II, which included cough, pruritus, insomnia, nausea, and fatigue. The mean gestation age for their infants was 39.2 weeks. HBsAg was positive in 28.6% of newborns but all became HBsAg negative at the age of 52 weeks after the appropriate immunoprophylaxis. No congenital defect was observed except for 1 infant, who had congenital umbilical hernia. Conclusions: In our cohort, mothers with chronic hepatitis B had excellent response to TDF during pregnancy. The therapy was well tolerated with no safety concerns. TDF treatment is effective not only in managing maternal disease, but also in preventing vertical transmission in mothers with high level of viremia. Further large multicenter studies are needed to verify our findings.

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Long Term Outcomes Of Entecavir And Tenofovir Combination Therapy For Chronic Hepatitis B Patients With Previous Nucleos(t)ide Treatment Failure Muzzaffar Gill* Sidra Gill, Ammara Nawaz, Misbah Malik, Faiza Irfan, Hafsa Aziz 1Gastroenterology Department Maroof International Hospital, Islamabad, Pakistan Background and Aims: Combination therapy with Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single regimen suitable for all patients who failed on other NUC regimens. We are presenting two year results of our ongoing study assessing ETV+TDF for patients with prior failure on NUC therapy. Methods: We prospectively enrolled 100 CHB patients with prior non-response, partial response, or virologic breakthrough on NUC therapy. They were treated with ETV (1 mg) plus TDF (300 mg) for 96 weeks. The primary endpoint was the proportion of patients with HBV DNA <50 IU/mL (Roche COBAS TaqMan-HPS Assay) at Week 48 (non-complete = failure). Secondary endpoints included proportions of patients with antiviral resistance and side effects responses at Week 96. Results: Overall, 100 patients were treated; 10 patients discontinued prior to Week 96. At baseline, 65% of patients were HBeAg (+), median HBV DNA was 4 log10 IU/ml. Prior NUC treatment included monotherapy with Lamuvidine(LVD) (53%), Adefovir(ADV) (20%), or combinations of these agents (27%). At Week 48, 76% of patients achieved the primary endpoint (HBV DNA <50 IU/mL). By Week 96, 85% of patients had HBV DNA <50 IU/mL, including 80% with prior failure on LVD, 100% on ADV, and 83% on combination therapy. Six patients had on-treatment serious adverse events, none of which were considered related to study treatment. One patient died from hepatocellular carcinoma. Conclusions: In patients who failed prior NUC therapy, Two years of ETV+TDF combination therapy was well tolerated and achieved virologic suppression in the majority (85%) of patients, irrespective of the type of prior NUC, with no new resistance development.

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Elevated Serum Levels of ALT Are Associated With Metabolic Syndrome Independent of Fatty Liver Diagnosed By Ultrasound Muzzaffar Gill, Sidra Gill, Ammara Nawaz, Misbah Malik, Faiza Irfan Gastroenterology Division, Maroof International Hospital, Islamabad, Pakistan Background and Aims: Elevated levels of alanine aminotransferase (ALT), a surrogate marker of liver injury, are mainly due to fatty liver (FL) and are considered an indicator of metabolic syndrome (MS). However, limited information is available on the influence of FL on this association between elevated ALT and MS. Methods: Individuals receiving medical examinations who are negative for both HBs-antigen and HCV antibody were enrolled (500men and 500women). ALT >30IU/L was considered elevated. FL was diagnosed using ultrasonography (US-FL). Results: There were 27.5% men and 20%women with elevated ALT. Logistic regression analysis revealed that obesity (odds ratios [95% confidence interval] 2.09 [1.77–2.45] among men and 2.31 [1.72–3.13] among women), dyslipidemia (1.90 [1.67–2.17] and 1.88 [1.42–2.40]), hypertension (1.33 [1.16–1.52] among men), and US-FL (3.34 [2.92–3.84] and 3.91 [3.00–5.12]) were independent predictors of elevated ALT. It is noteworthy that among the subjects with elevated ALT, approximately one-third men and women did not have US-FL. The risk of elevated ALT increased with the number of MS components in both of US-FL(−) and US-FL(+) subjects Conclusions: There is an independent association between the risk of elevated ALT and the number of MS components regardless of the presence of US-FL, suggesting the importance of MS in the pathogenesis of liver injury.
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