Effectiveness and tolerability of simeprevir and sofosbuvir in nontransplant and post-liver transplant patients with hepatitis C genotype 1.

BACKGROUND: Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis and post-transplant status are historically associated with poor treatment responses. The new oral direct-acting agents appear to be effective and safe in these patients. AIMS: To evaluate the effectiveness and tolerability of simeprevir and sofosbuvir in a diverse real-life cohort of patients, including difficult-to-treat patients. METHODS: We conducted a retrospective cohort study in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50 post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks between December 2013 and December 2014. Primary outcome was sustained virological response with undetectable HCV RNA 12 weeks after completion of therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs. 1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis). RESULTS: SVR12 rates were similar in non- and post-transplant settings, 82% and 88%, respectively. There were no significant differences in adverse events in patients regardless of cirrhosis or transplant status. On multivariate analysis also inclusive of gender and liver transplant status, negative predictors of SVR12 were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10-0.87, P = 0.027 or 0.29, 95% CI 0.09-0.85, P = 0.025, respectively). CONCLUSION: Simeprevir and sofosbuvir combination is a safe and effective regimen for the treatment of non- and post-transplant patients with traditional risk factors for poor treatment response, unless more than 2 difficult-to-treat risk factors are present.

Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response.

BACKGROUND: Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. AIM: To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses. METHODS: A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated. RESULTS: Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups. CONCLUSION: A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.

Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. AIM: To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. METHODS: Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. RESULTS: Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. CONCLUSION: Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.

Childhood dengue shock syndrome in Trinidad.

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is a major cause of hospitalisation and mortality among children in South East Asia. We now report, for the first time, the occurrence of DHF/DSS in Trinidadian children. The presence of vomiting, abdominal pain and hepatomegaly in the setting of a dengue epidemic should alert clinicians to the possibility of DHF/DSS. Timely diagnosis and aggressive supportive treatment are essential for a successful outcome. Source reduction, vector control and community participation are also necessary to avert the South East Asian scenario from emerging in the Caribbean.

Childhood dengue shock syndrome in Trinidad

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is a major cause of hospitalisation and mortality among children in South East Asia. We now report, for the first time, the occurrence of DHF/DSS in Trinidadian children. The presence of vomitting, abdominal pain and hepatomegaly in the setting of a dengue epidemic should alert clinicians to the possibility of DHF/DSS. Timely diagnosis and aggressive supportive treatment are essential for a successful outcome. Source reduction, vector control and community participation are also necessary to avert the South East Asian scenario from emerging in the Caribbean (AU)

Childhood dengue shock syndrome in Trinidad

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is a major cause of hospitalisation and mortality among children in South East Asia. We now report, for the first time, the occurrence of DHF/DSS in Trinidadian children. The presence of vomiting, abdominal pain and hepatomegaly in the setting of a dengue epidemic should alert clinicians to the possibility of DHF/DSS. Timely diagnosis and aggressive supportive treatment are essential for a successful outcome. Source reduction, vector control and community participation are also necessary to avert the South East Asian scenario from emerging in the Caribbean.

The role of intracaval filters in patients with COPD and DVT.

A retrospective study of the Coney Island Hospital experience with Greenfield filters over a five-year period was undertaken. During this period, a total of 78 intracaval filters were placed in 76 patients. The patients' charts were reviewed for (1) indication for Greenfield filter placement, (2) complications of the procedure, (3) associated medical problems, and (4) follow-up information. The data revealed one statistically significant subpopulation within the group that had particularly poor survival statistics after intracaval filter insertion. These were patients who had a pulmonary embolism and also had chronic obstructive pulmonary disease (COPD). Considering the low morbidity associated with this procedure, it is the author's feeling that prophylactic intracaval filters in patients with deep vein thrombosis and COPD may be warranted.

A 5-year follow-up of undiagnosed haematuria.

Eighty-four patients with haematuria were seen during 1976 and 1977. This symptom was investigated but no definite cause could be found. Five or more years later they were followed up. Although some patients had experienced further urological symptoms, none was found to have developed a malignancy in the genito-urinary tract. Possible causes of their bleeding are discussed.