Hector E. Nazario

Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min.

Treating chronic hepatitis C (CHC) in patients with end‐stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC‐infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population.

Safety and efficacy of simeprevir plus sofosbuvir with or without ribavirin in patients with decompensated genotype 1 hepatitis C cirrhosis.

Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End‐Stage Liver Disease score was 12 (range, 6‐25). Treatment was well tolerated overall with more than one‐half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12. Liver Transpl 22:281‐286, 2016.

The Long-Term Use of Statins Is Associated with a Decreased Incidence of Adenomatous Colon Polyps

Background/Aims: Studies have suggested that statins may protect against colorectal cancer (CRC), but it is not clear whether that protection results from effects on established adenomatous polyps (APs) or from preventing the development of new APs. We have conducted a retrospective, cohort study to explore how the long-term use of statins influences the development of new APs. Methods: We reviewed endoscopy and pathology databases to identify patients with histologically verified APs, all of which were removed during an index colonoscopy, and who had a follow-up colonoscopy 3–5 years later. Patients were categorized as users or nonusers of statins by review of their medical and pharmacy records, and the characteristics of APs found on follow-up colonoscopy in the 2 groups was compared. Results: We identified 2,626 patients (84% men, mean age 62.2 years) with APs removed during an index colonoscopy. Of 1,688 patients (35%) who used statins continuously, 583 had an AP found on follow-up colonoscopy, compared to 477 of 938 patients (51%) who did not use statins continuously [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43–0.60; p < 0.01]. Statin use was associated with a smaller mean number of polyps (2.6 vs. 3.1; p = 0.002), a smaller mean polyp size (7.1 vs. 7.9 mm; p = 0.03) and a significant reduction in the incidence of advanced APs (OR 0.74, 95% CI 0.52–0.96; p = 0.03). Conclusions: In patients with APs removed colonoscopically, long-term statin usage is associated with a decreased incidence of new and advanced APs. This suggests that statins may protect against CRC by reducing the development of new APs.

Reduction in Low-Density Lipoprotein Cholesterol Levels During Statin Therapy Is Associated With a Reduced Incidence of Advanced Colon Polyps

Background:Elevated serum cholesterol levels may stimulate proliferation in adenomatous polyps (AP). Our aim was to determine how a reduction of low-density lipoprotein (LDL) cholesterol levels in patients taking statins influences the incidence of APs. Methods:We performed a retrospective study of patients taking statins who were found to have ≥1 APs on an index colonoscopy, and who also had a follow-up colonoscopy within 3 to 5 years. Patients were divided into 2 groups: (1) those with ≥30% reduction in LDL levels and (2) those with <30% reduction in LDL levels during the interval between colonoscopies. Univariate and multivariate analysis were evaluated for their association with advanced APs. Results:We identified 231 patients. Univariate analysis showed that patients with ≥30% LDL reduction had fewer mean total numbers of APs (2.6 versus 3.3, P = 0.02), fewer advanced APs (14% versus 26%, P = 0.04), and smaller APs (5 mm versus 6.1 mm, P = 0.01) than those with <30% reduction in LDL. Multiple logistic regression analysis confirmed that ≥30% LDL reduction was associated with smaller APs (P < 0.01). Subjects with ≥30% LDL reduction also had a 53% reduced incidence of advanced APs (OR, 0.47; CI, 0.22–0.96; P < 0.05). These findings remained significant even when adjusted for nonsteroidal antiinflammatory drug use, age, family history of APs, and body mass index. Conclusions:A reduction in LDL levels of ≥30% during a 3- to 5-year period of statin therapy was associated with a 53% reduction in the incidence of advanced APs, even after adjustment for other known polyp risk factors.

Liver Transplantation for Hepatocellular Carcinoma (Hcc)

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide and accounts for 20% of all liver transplants (Wigg, 2010). Its incidence has increased two fold in the last decade and it is the fifth leading cause of cancer in males. The availability of liver transplantation as a cure for chronic liver disease and the demonstration of outcomes exceeding 70% at 5 years after transplantation for HCC have pushed the field to refine this therapy in order to utilize this precious resource in the most effective, fair and safe manner. The combination of a rising incidence of HCC and a flat donor procurement rates has resulted in longer waiting times in many areas. The complex decision making and management issues of patients with HCC, cirrhosis and possibly undergoing oncological therapies while waiting for an organ transplant poses challenges to the management team, not encountered in any other clinical or surgical field.