Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance.

AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ALT. METHODS: This was a retrospective study of chronic hepatitis B patients on lamivudine therapy who were followed for 3-mo with liver function tests and hepatitis B virus (HBV) DNA measurement. Lamivudine resistance was defined as HBV DNA ≥ 1 log from nadir on at least 2 occasions, confirmed by genotyping. Serum ALT levels in patients with lamivudine resistance were compared to serum ALT levels in those without lamivudine resistance. RESULTS: There were 111 patients with and 117 without lamivudine resistance. The area under the receiver operating characteristic of serum ALT to diagnose lamivudine resistance was 0.645 ± 0.037. Serum ALT > 42.5 U/L gave the best diagnostic accuracy with sensitivity = 61%, specificity = 60%, positive predictive value = 60%, negative predictive value = 61%, positive likelihood ratio = 1.53 and negative likelihood ratio = 0.65 for predicting lamivudine resistance, missing 39% of resistant patients. Using other serum ALT cutoffs, diagnostic accuracy was lower. By multivariate analysis, baseline abnormal serum ALT was associated with abnormal ALT during resistance (OR = 5.98, P = 0.003), and males were associated with serum ALT flares during resistance (OR = 8.9, P = 0.016). CONCLUSION: Serum ALT is inadequate for diagnosing lamivudine resistance and has implications where viral resistance testing is suboptimal and for reimbursement of rescue therapy.

The response of Asian patients with functional dyspepsia to eradication of Helicobacter pylori infection.

OBJECTIVES/BACKGROUND: The role of Helicobacter pylori infection in functional dyspepsia (FD) remains controversial. Several randomized controlled trials involving populations in the West, observed no statistically significant advantage over placebo. However, none of these studies involved Asian populations which have high infection rates. METHODS: A double blind, randomized, placebo-controlled trial of H. pylori eradication for FD was conducted in our Singapore-based Asian population. Forty-one patients received active treatment consisting of a 1-week course of omeprazole 20 mg once daily, clarithromycin 250 mg twice daily and tinidazole 500 mg twice daily whereas another 41 patients received matching placebo tablets. A dyspepsia score was derived by grading 5 dyspeptic symptoms on a Likert scale. Symptom assessment and urea breath test were repeated at 6 weeks, 6 and 12 months from the start of treatment. The primary end point was symptom resolution, defined as a dyspepsia score of 0 or 1 at the end of 12 months follow-up. RESULTS: On intention-to-treat analyses, symptom resolution was observed in 24% of patients on active treatment and 7% on placebo; the difference in proportion of patients with symptom resolution was statistically significant (P=0.02, 95% confidence interval: 1.1-17.7). H. pylori eradication rates perprotocol and intention-to-treat were 80.0 and 68.3%, on active treatment and 5.6 and 4.9% on placebo (both P values<0.0001). Among patients with H. pylori eradicated on active treatment the symptom resolution rate was 39% (10 of 26), whereas it was 3% (one of 35) among patients in the placebo group who had persistent H. pylori infection. In multivariate analysis, posttreatment H. pylori status was the only predictor of symptom resolution. The majority of patients, 91.5%, had ulcer-like dyspepsia; heartburn and acid regurgitation were uncommon, and no increase was observed after treatment. CONCLUSION: In contrast to Western populations, our results suggest that patients with FD in Asia would benefit from treatment for H. pylori infection with as much as a 13-fold increased chance of symptom resolution following its eradication.

Prevalence and clinical associations of posttransplant fatty liver disease.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) could recur after liver transplant in patients with preexisting NAFLD, and has recently been reported to occur after transplant in patients transplanted without preexisting NAFLD. The literature on posttransplant NAFLD is limited. We aimed to study the prevalence of posttransplant NAFLD in patients transplanted for non-NAFLD-related liver diseases. METHODS: Thirty liver transplant recipients: 18 with chronic hepatitis B (CHB), seven with chronic hepatitis C (CHC), five others, were recruited. Liver biopsies were performed in all CHB and CHC patients annually as per protocol, or when clinically indicated. All biopsies were reviewed by one hepato-histopathologist blindly to assess and stage for steatosis and steatohepatitis. RESULTS: After a mean follow-up of 44+/-4 months, 12 (40%) and four (13%) developed posttransplant steatosis and steatohepatitis, respectively. None developed steatosis-related fibrosis or cirrhosis. Posttransplant steatohepatitis was associated with higher pretransplant body mass index (BMI) (32.3+/-3.9 vs 23.1+/-0.8, P=0.02) and higher BMI at last biopsy (32.5+/-4.3 vs 22.9+/-0.7, P=0.01). CONCLUSION: Posttransplant steatosis is common after liver transplant even in patients transplanted for non-NAFLD-related liver diseases. However, it is mostly benign during our follow-up, with only 13% developing steatohepatitis and none with fibrosis or cirrhosis.

A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B.

Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-alpha, and thymosin-alpha1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-alpha1, 1.6 microg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) > or = 1.5 x upper normal limit, but < or = 10 x upper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P = 0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.

Outcome from molecular adsorbent recycling system (MARS) liver dialysis following drug-induced liver failure.

RATIONALE: Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. RESULTS: A total of 13 patients were treated, and 40 sessions of MARS liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS was 8 days. CONCLUSIONS: MARS liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

Outcome of lamivudine-resistant hepatitis B virus is generally benign except in cirrhotics.

AIM: We set to determine factors that determine clinical severity after the development of resistance. METHODS: Thirty-five Asian patients with genotypic lamivudine resistance were analyzed in three groups: 13/35 (37%) were non-cirrhotics with normal pre-treatment ALT (Group IA), 12/35 (34%) were non-cirrhotics with elevated pre-treatment ALT (Group IB), and 10/35 (29%) were cirrhotics (Group II). Patients were followed for a median of 98 wk (range 26-220) after the emergence of genotypic resistance. RESULTS: Group IA patients tended to retain normal ALT. Group IB patients showed initial improvement of ALT with lamivudine but 9/12 patients (75%) developed abnormal ALT subsequently. On follow-up however, this persisted in only 33%. Group II patients also showed improvement while on treatment, but they deteriorated with the emergence of resistance with 30% death from decompensated liver disease. Pretreatment ALT levels and CPT score (in the cirrhotic group) were predictive of clinical resistance and correlated with peak ALT levels and CPT score. CONCLUSION: The phenotype of lamivudine-resistant HBV correlated with the pretreatment phenotype. The clinical course was generally benign in non-cirrhotics. However, cirrhotics had a high risk of progression and death (30%) with the development of lamivudine resistance.

Remember to crush the tablets after esophageal stent insertion.

The main mode of palliation for inoperable esophageal cancer is by insertion of expandable metallic stents. While major complications include occlusion by tumor ingrowth and migration, impaction by food has been reported in as many as 10% of cases. Although patients are routinely instructed to follow a soft and finely minced diet after insertion of esophageal stents, stent blockage can still occur if patients swallow large-sized tablets. We report a case of stent blockage by 2 large-sized tablets, about which the endoscopist did not forewarn the patient or his family. The tablets were eventually dislodged easily through a repeat endoscopy. We caution about the possibility of such complication after esophageal stenting. We recommend inspection of patients' medication before the stenting procedure as well as instructing patients, their family, and care providers to crush their large-sized tablets before consumption.